CN103180332A - N-heterocyclic carbene complexes, their preparation and use - Google Patents

N-heterocyclic carbene complexes, their preparation and use Download PDF

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CN103180332A
CN103180332A CN2011800521874A CN201180052187A CN103180332A CN 103180332 A CN103180332 A CN 103180332A CN 2011800521874 A CN2011800521874 A CN 2011800521874A CN 201180052187 A CN201180052187 A CN 201180052187A CN 103180332 A CN103180332 A CN 103180332A
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A·S·K·哈什米
C·洛特舒尔茨
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    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
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    • B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
    • B01J2231/4266—Sonogashira-type, i.e. RY + HC-CR' triple bonds, in which R=aryl, alkenyl, alkyl and R'=H, alkyl or aryl
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    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination
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Abstract

N-heterocyclic carbene complexes of the formula (I) is disclosed, wherein the radicals have the meanings as defined in the invention. The preparation and the use as catalysts employed in a C-C, C-O, C-N or C-H bond formation reaction of said complexes are also disclosed.

Description

N-heterocycle carbine title complex, its preparation and application
Background of invention
The present invention relates to N-heterocycle carbine title complex, its preparation method and as the purposes of catalyzer.
Description of Related Art
In nineteen sixty-eight, H.W.Wanzlick and K.
Figure BDA00003115671900011
independently reported and there is directly synthetic first as the metal complexes of part of N-heterocycle carbine (NHC).Can predict that no one at that time these parts are in role decades subsequently.Especially the NHC title complex of Pd (II) has found wide in range application in organic and organometallic chemistry of modern times.With other parts, as phosphine, compare, the advantage of NHC has been as thermostability, hypotoxicity, allowed the NHC title complex to be applied to many different linked reactions to the unwise property of oxygen, such as Heck, Sonogashira, Suzuki-Miyaura, Stille, Hartwig-Buchwald coupling etc.Especially the Suzuki-Miyaura reaction is at present because stability, availability and the hypotoxicity of boric acid class used play an important role.
Except for catalysis, the NHC title complex can also be for many other fields as medical use, nano particle, supramolecular chemistry, self-assembly, photochemistry, liquid crystal, polymerization and electronically active material.
Except the dramatic benefit of these particular ligand, the synthetic of saturated NHC title complex still faced the challenge.A.J.Arduengo, R.Krafczyk and R.Schmutzler are at Tetrahedron1999, described in 55,14523-14534 by oxalic dialdehyde and started via corresponding diimine and diamines dihydrochloride synthetic inferior imidazolidine base class (imidazolylidene), inferior tetrahydroglyoxaline base class (imidazolinylidene) and imidazoles alkanes.Then by with as C 1the ortho-formiate reaction of structural unit changes into corresponding tetrahydroglyoxaline by the diamines dihydrochloride
Figure BDA00003115671900012
salt.With this tetrahydroglyoxaline of lithium aluminium hydride reduction
Figure BDA00003115671900013
salt obtains the imidazoles alkanes, and obtains corresponding tetrahydroglyoxaline-2-subunit class with the potassium hydride KH deprotonation.Yet the method does not especially allow to form the NHC of Asymmetrical substitute.
B.A.Bhanu Prasad and S.R.Gilbertson, at Org.Lett.2009, have described in 11,3710-3713 by the synthetic asymmetric NHC part of N-(2-iodine ethyl) aryl amine salt list still.This approach is limited to the NHC that formation has specified substituent.
Known use isonitrile metal complexes forms acyclic or ring-type Cabbeen.
K.Bartel and W.P.Fehlhammer be at Angew.Chem.Int.Ed.1974, described reaction by 2-and 3-hydroxyalkyl isocyanide metallizing thing in 13,599-600 and formed Pd, Pt and Au
Figure BDA00003115671900021
azoles alkane subunit and perhydro
Figure BDA00003115671900022
piperazine subunit (oxazinylidene) title complex.
U.Plaia and W.P.Fehlhammer be at J.Am.Chem.Soc.1985, described six in 107,2171-2172 (
Figure BDA00003115671900023
azoles alkane-2-subunit) cobalt (III) and-preparation of rhodium (III).
M.Tamm and F.E.Hahn be at Coord.Chem.Rev.1999, described in 182,175-209 by the β of coordination-sense phenyl isocyanide and formed arbine complex.
R.A.Michelin, L.Zanotto, D.Braga, P.Sabatino and R.J.Angelici are at Inorg.Chem.1988, cyclic amino oxygen base arbine complex via the synthetic Pt (II) of cyclization of isocyanide title complex and ethylene bromohyrin has been described in 27,85-92.
I.Yu, C.J.Wallis, B.O.Patrick, P.L.Diaconescu and P.Mehrkhodavandi have reported a little correlated response in doi:10.1021/om100841j, it uses primary amine and the activation of the bacterial strain on iron (strain-activated) isonitrile/phosphine inner complex.
R.A.Michelin, L.Zanotto, D.Braga, P.Sabatino and R.J.Angelici are at Inorg.Chem.1988, ring-type diamino arbine complex via the synthetic Pd (II) of the cyclization of isocyanide title complex and 2-bromotrifluoromethane amine and Pt (II) has been described in 27,93-99.
R.A.Michelin, A.J.L.Pombeiro and M.F.C.Guedes da Silva, at Coord.Chem.Rev.2001, have reported the amino arbine complex be derived from the nucleophilic addition(Adn) of isocyanide part in 218,75-112.
After method described in 3 pieces of documents mentioning be provided on a nitrogen-atoms and do not replace and NHC that only alkyl substituent can be connected with this nitrogen-atoms subsequently.Free NHC synthetic usually to rectificate the organic synthesis step and so synthetic NHC part difficult with being connected usually of this metal and require extra synthetic effort.
Still be starved of a kind of permission and prepare N, the dibasic NHC title complex of N'-, the effective ways of especially asymmetric dibasic NHC title complex.This metal-NHC title complex is answered air-stable and is easy to and processes.
Have now found that surprising be this purpose by the omega-halogenated alkyl groups ammonium salt that makes to replace or ω-(carbalkoxy) alkylammonium salt with facilitate available isocyanide complex to react to realize.
Summary of the invention
The present invention relates to a kind of method for preparing the compound of general formula (I):
Figure BDA00003115671900031
Wherein
N is 0 or 1,
The group that M is the containing metal atom,
R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R 2be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R wherein 1and R 2mean hydrogen when different,
R 3and R 4independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Perhaps R 3and R 4with together with the carbon atom of their institute's bondings, be C=O,
Perhaps R 3for group O-R 3aand
For n=0, R 4and R 7mean to be equal to respectively with R 4and R 7carbon atom between the key of two keys, or
For n=1, R 4and R 5mean to be equal to respectively with R 4and R 5carbon atom between the key of two keys, wherein
R 3afor the group via carbon atom, Siliciumatom, sulphur atom, phosphorus atom, boron atom or titanium atom and oxygen bonding,
R 5, R 6, R 7and R 8independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Two radicals R wherein 2and R 8can also and R 2the N atom of institute's bonding forms together can optionally have 1,2 or 3 independently selected from O, N, NR awith other heteroatomss of S or containing heteroatom group the 3-12 person's nitrogen heterocyclic that does not replace or replace as ring members, wherein R afor hydrogen, alkyl, cycloalkyl or aryl,
Perhaps
If wherein n=0, R 4and R 7can also mean to be equal to R 4and R 7carbon atom between the key of two keys,
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With general formula (III) or compound (IIIa), react:
Figure BDA00003115671900041
Wherein
N, R 2, R 3, R 4, R 5, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y is leavings group, or
If R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, Y is group O-Y a, Y wherein afor the alkyl that does not replace or replace, the aryl that does not replace or replace, the aryl carbonyl that does not replace or replace or the alkyl-carbonyl that does not replace or replace, and
B1) optionally, if R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, make at step a1) in the product that obtains and compound R that wherein Z is leavings group 3a-Z is further reaction under alkali exists, and obtains wherein R 3for group O-R 3aand for n=0, R 4and R 7mean to be equal to and R 4and R 7the key of the two keys between the carbon atom of bonding or for n=1, R 4and R 5mean to be equal to and R 4and R 5the formula of the key of the two keys between the carbon atom of bonding (I) compound,
Perhaps
A2) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With the compound of logical formula V, react:
Figure BDA00003115671900051
Wherein
R 2, R 3and R 8above having to one of implication; And
R 10and R 11independently selected from C 1-C 4alkyl or R 10and R 11be can be by one or more C together 1-C 4the linear C that alkyl replaces 2-C 4alkylidene group;
Obtain the midbody compound of formula (VI):
Figure BDA00003115671900052
And
B2), with the midbody compound of acid treatment formula (VI), wherein in the compound obtained according to this scheme (I), n is 0 and R 4and R 7mean to be equal to R 4and R 7carbon atom between the key of two keys;
Perhaps
A3) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With general formula (IIIb) or compound (IIIc), react:
Figure BDA00003115671900061
Wherein
R 2, R 4, R 7and R 8above having to one of implication;
X -for the negatively charged ion Equivalent; And
EWG is (C (O) R 14, C (O) OR 14, NO 2, S (O) R 14or S (O) 2r 14, R wherein 14for hydrogen, alkyl, cycloalkyl or aryl;
Wherein according to scheme a3) in the compound (I) that obtains, n is 0 and R 3for CH 2-EWG.
In first aspect, the invention provides a kind of method for preparing the compound of general formula (I):
Figure BDA00003115671900062
Wherein
N is 0 or 1,
The group that M is the containing metal atom,
R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R 2be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R wherein 1and R 2mean hydrogen when different,
R 3and R 4independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Perhaps R 3and R 4with together with the carbon atom of their institute's bondings, be C=O,
Perhaps R 3for group O-R 3aand for n=0, R 4and R 7mean to be equal to respectively with R 4and R 7carbon atom between the key of two keys,
Perhaps R 3for group O-R 3aand for n=1, R 4and R 5mean to be equal to respectively with R 4and R 5carbon atom between the key of two keys, wherein
R 3afor the group via carbon atom, Siliciumatom, sulphur atom, phosphorus atom, boron atom or titanium atom and oxygen bonding,
R 5, R 6, R 7and R 8independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Two radicals R wherein 2and R 8can also and R 2n atom and the R of institute's bonding 8the carbon atom of institute's bonding forms together can optionally have 1,2 or 3 independently selected from O, N, NR awith other heteroatomss of S or containing heteroatom group the 3-12 person's nitrogen heterocyclic that does not replace or replace as ring members, wherein R afor hydrogen, alkyl, cycloalkyl or aryl,
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With general formula (III) or compound (IIIa), react:
Figure BDA00003115671900071
Wherein
N, R 2, R 3, R 4, R 5, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y is leavings group, or
If R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, Y is group O-Y a, Y wherein afor the alkyl that does not replace or replace, the aryl that does not replace or replace, the aryl carbonyl that does not replace or replace or the alkyl-carbonyl that does not replace or replace, and
B1) optionally, if R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, make at step a1) in the product that obtains and compound R that wherein Z is leavings group 3a-Z is further reaction under alkali exists, and obtains wherein R 3for group O-R 3aand for n=0, R 4and R 7mean to be equal to and R 4and R 7the key of the two keys between the carbon atom of bonding or for n=1, R 4and R 5mean to be equal to and R 4and R 5the formula of the key of the two keys between the carbon atom of bonding (I) compound.
According to particular embodiments, the inventive method is used to form the Asymmetrical substitute compound of formula (I).In this embodiment, preferred R 1and R 2there are different implications.
The first scheme is the method for a kind of preparation formula (I-A.1) or compound (I-A.2):
Figure BDA00003115671900081
Wherein
M, R 1, R 2, R 5, R 6, R 7and R 8have as top and following defined implication,
R 3and R 4independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M (II)
R wherein 1with M, have as one of top and following defined implication,
With general formula (III) or compound (IIIa), react:
Figure BDA00003115671900091
Wherein
N, R 2, R 3, R 4, R 5, R 6, R 7and R 8have as one of top and following defined implication,
X -for the negatively charged ion Equivalent, and
Y is leavings group.
Alternative plan is a kind of method for preparing general formula (I-B.1) or compound (I-B.2):
Figure BDA00003115671900092
Wherein
M, R 1, R 2, R 5, R 6, R 7and R 8have as top and following defined implication, the method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M (II)
R wherein 1with M, have as one of top and following defined implication,
With general formula (III-B.1), (III-B.1.a), (III-B.2) or compound (III-B.2.a), react:
Figure BDA00003115671900093
Wherein
R 2, R 5, R 6, R 7and R 8have as one of top and following defined implication,
X -for the negatively charged ion Equivalent, and
Y afor the alkyl that does not replace or replace, the aryl that does not replace or replace, the aryl carbonyl that does not replace or replace or the alkyl-carbonyl that does not replace or replace.
In the situation that general formula (I-B.1) or ketone compound (I-B.2) can form tautomer, those tautomers are also a part of the present invention.
Third party's case is a kind of method for preparing general formula (I-C.1) or compound (I-C.2):
Figure BDA00003115671900101
Wherein
M, R 1, R 2, R 3a, R 6, R 7and R 8have as top defined implication,
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With general formula (III-C.1), (III-C.1.a), (III-C.2) or compound (III-C.2.a), react:
Figure BDA00003115671900102
Wherein
R 2, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y afor the alkyl that does not replace or replace, the aryl that does not replace or replace, the aryl carbonyl that does not replace or replace or the alkyl-carbonyl that does not replace or replace, and
B1) make at step a1) in the product that obtains and compound R that wherein Z is leavings group 3a-Z is further reaction under alkali exists.
In second aspect, (formula I compound, wherein n is 0 and R to the invention provides a kind of compound for preparing general formula (I-E) 4and R 7mean to be equal to R 4and R 7carbon atom between the key of two keys) method:
Figure BDA00003115671900111
Wherein
The group that M is the containing metal atom,
R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R 2be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R wherein 1and R 2mean hydrogen when different,
R 3alkyl, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino of being selected from hydrogen and not replacing in each case or replace
R 8alkyl, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino of being selected from hydrogen and not replacing in each case or replace
Two radicals R wherein 2and R 8can also and R 2the N atom of institute's bonding forms together can optionally have 1,2 or 3 independently selected from O, N, NR awith other heteroatomss of S or containing heteroatom group the 3-12 person's nitrogen heterocyclic that does not replace or replace as ring members, wherein R afor hydrogen, alkyl, cycloalkyl or aryl,
The method comprises:
A2) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With the compound of logical formula V, react:
Figure BDA00003115671900121
Wherein
R 2, R 3and R 8above having to one of implication; And
R 10and R 11independently selected from C 1-C 4alkyl or R 10and R 11be can be by one or more together, 1,2,3,4,5 or 6 C for example 1-C 4the linear C that alkyl replaces 2-C 4alkylidene group;
Obtain the midbody compound of formula (VI):
Figure BDA00003115671900122
R wherein 1, R 2, R 3, R 8, R 10, R 11with M as defined above;
And
B2) use the midbody compound of acid treatment formula (VI).
According to particular embodiments, be used to form the Asymmetrical substitute compound of formula (I-E) according to the inventive method of second aspect.In this embodiment, preferred R 1and R 2there are different implications.
In the third aspect, (formula I compound, wherein n is 0 and R to the invention provides a kind of compound for preparing general formula I-F 3for CH 2-EWG) method:
Figure BDA00003115671900123
R wherein 1, R 2, R 4, R 7, R 8, M and EWG above having to one of implication,
The method comprises:
A3) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication
With general formula (IIIb) or compound (IIIc), react:
Figure BDA00003115671900131
Wherein
EWG, R 2, R 4, R 7and R 8above having to one of implication; And
X -for the negatively charged ion Equivalent.
According to particular embodiments, be used to form the Asymmetrical substitute compound of formula (I-F) according to the inventive method of this third aspect.In this embodiment, preferred R 1and R 2there are different implications.
On the other hand, the invention provides the new compound of general formula (I).
On the other hand, the invention provides the new compound of general formula (VI).
On the other hand, the invention provides a kind of compound that comprises general formula (I) or the catalyzer formed by it.
On the other hand, the invention provides purposes or the purposes in this catalyzer of the compound of general formula (I) as used catalyst in C-C, C-O, C-N or c h bond formation reaction.
According to particular embodiments, the compound of general formula (I) is used for being selected from the C-C linked reaction that Suzuki reacts, Heck reacts, Sonogashira reacts, Stille reacts, Hartwig-Buchwald reacts and Kumada reacts.
According to another particular embodiments, the compound of general formula (I) is reacted or the acid amides alpha-aromatic for hydrogenation, hydroformylation, hydrosilylation, Hartwig-Buchwald.
Invention is described
For the purpose of the present invention, term N-heterocycle carbine (NHC) means the compound can existed with different resonance structure forms, described resonance structure for example by the structure with dicovalent carbon atom and in
Figure BDA00003115671900133
salt type representation.
The preferred embodiment of the compound of general formula (I) be as top and hereinafter as shown in formula (I-A.1), (I-A.2), (I-B.1), (I-B.2), (I-C.1) and (I-C.2) compound.The definition of all compounds about general formula (I) also can be used for formula (I-A.1), (I-A.2), (I-B.1), (I-B.2), (I-C.1) and compound (I-C.2), unless clearly definition separately arranged.The preferred embodiment of the compound of general formula (I) also has as above and hereinafter formula shown (I-E) and compound (I-F).The definition of all compounds about general formula (I) also can be used for formula (I-E) and compound (I-F), unless clearly definition separately arranged.
In the context of the invention, use M-C in singly-bound expression (I) and compound (VI) cabbeeninteract.
Statement " halogen " means fluorine, bromine, chlorine or iodine, particularly chlorine, bromine or iodine in each case.
In the context of the invention, the statement " alkyl that does not replace or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, the heterocycle alkoxyl group, the heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino, (two heteroaryls) amino " mean the alkyl that does not replace or replace, the alkoxyl group that does not replace or replace, the alkylthio that does not replace or replace, (monoalkyl) amino that does not replace or replace, (dialkyl group) amino that does not replace or replace, the cycloalkyl that does not replace or replace, the cycloalkyloxy that does not replace or replace, the cycloalkylthio that does not replace or replace, (monocycle alkyl) amino that does not replace or replace, (bicyclic alkyl) amino that does not replace or replace, the Heterocyclylalkyl that does not replace or replace, the heterocycle alkoxyl group that does not replace or replace, the heterocycle alkylthio that does not replace or replace, (single Heterocyclylalkyl) amino that does not replace or replace, (two Heterocyclylalkyls) amino that does not replace or replace, the aryl that does not replace or replace, the aryloxy that does not replace or replace, the arylthio that does not replace or replace, (single aryl) amino that does not replace or replace, (diaryl) amino that does not replace or replace, the heteroaryl that does not replace or replace, the heteroaryloxy that does not replace or replace, the heteroarylthio that does not replace or replace, amino and (two heteroaryls) amino that do not replace or replace of (the single heteroaryl) that does not replace or replace.
In the context of the invention, statement " alkyl " comprises straight chain or branched-alkyl.Alkyl is preferably C 1-C 30alkyl, more preferably C 1-C 20alkyl, most preferably C 1-C 12alkyl.The example of alkyl is methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, n-pentyl, neo-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, positive decyl, n-undecane base, dodecyl, n-tridecane base, n-tetradecane base, n-hexadecyl, Octadecane base and NSC 62789 base especially.
The statement alkyl also comprise its carbochain can by one or more being selected from-O-,-S-,-NR b-,-C (=O)-,-S (=O)-and/or-S (=O) 2-the alkyl at non-adjacent group interval.R bbe preferably hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl.
The alkyl replaced depends on that the length of alkyl chain can have one or more (for example 1,2,3,4,5 or be greater than 5) substituting group.These preferably are selected from cycloalkyl, Heterocyclylalkyl, aryl, heteroaryl, fluorine, chlorine, bromine, hydroxyl, sulfydryl, cyano group, nitro, nitroso-group, formyl radical, acyl group, COOH, carboxylic acid compound group, alkyl carbonyl oxy, formamyl, SO independently of one another 3h, azochlorosulfonate acid compound group, sulfamyl, sulphonamide, amidino groups, NE 1e 2, E wherein 1and E 2be hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl independently of one another.The cycloalkyl of alkyl, Heterocyclylalkyl, aryl and heteroaryl substituting group can be again not replace or replace; Suitable substituting group is the following substituting group that these groups are mentioned.
Carboxylic acid compound and azochlorosulfonate acid compound mean respectively carboxylic acid functional and sulfonic acid functional group's derivative, especially metal carboxylate or sulfonate, carboxylicesters or sulfonate functionality or carboxylic acid amides or sulphonamide functional group.
Above-mentioned explanation about alkyl also is applicable to the alkyl structure part in alkoxyl group, alkylthio (=alkyl sulfenyl), alkyl monosubstituted amino and dialkyl amido.
In the context of the invention, term " cycloalkyl " means usually have 3-20, preferably 3-12, more preferably the list of 5-12 carbon atom-, two-or tricyclic hydrocarbon base, as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group, cyclo-dodecyl, cyclopentadecane base, norcamphyl, dicyclo [2.2.2] octyl group or adamantyl.
The cycloalkyl replaced depends on that ring size can have one or more (for example 1,2,3,4,5 or be greater than 5) substituting group.These preferably are selected from alkyl, alkoxyl group, alkylthio, cycloalkyl, Heterocyclylalkyl, aryl, heteroaryl, fluorine, chlorine, bromine, hydroxyl, sulfydryl, cyano group, nitro, nitroso-group, formyl radical, acyl group, COOH, carboxylic acid compound group, alkyl carbonyl oxy, formamyl, SO independently of one another 3h, azochlorosulfonate acid compound group, sulfamyl, sulphonamide, amidino groups, NE 3e 4, E wherein 3and E 4be hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl independently of one another.In the situation that replace, cycloalkyl is preferably with one or more, for example 1,2,3,4 or 5 C 1-C 6alkyl.The example of substituted cycloalkyl is 2-and 3-methylcyclopentyl especially, 2-and 3-ethyl cyclopentyl, 2-, 3-and 4-methylcyclohexyl, 2-, 3-and 4-ethyl cyclohexyl, 2-, 3-and 4-propyl group cyclohexyl, 2-, 3-and 4-isopropylcyclohexyl-, 2-, 3-and 4-butyl cyclohexyl, 2-, 3-and 4-sec-butyl cyclohexyl, 2-, 3-and 4-tert-butylcyclohexyl, 2-, 3-and 4-methyl suberyl, 2-, 3-and 4-ethyl suberyl, 2-, 3-and 4-propyl group suberyl, 2-, 3-and 4-sec.-propyl suberyl, 2-, 3-and 4-butyl suberyl, 2-, 3-and 4-sec-butyl suberyl, 2-, 3-and 4-tertiary butyl suberyl, 2-, 3-, 4-and 5-methyl ring octyl group, 2-, 3-, 4-and 5-ethyl ring octyl group, 2-, 3-, 4-and 5-propyl group ring octyl group.
Above-mentioned explanation about cycloalkyl also is applicable to the cycloalkyl structure division in cycloalkyloxy, cycloalkylthio (=cycloalkyl sulfenyl), monocycle alkylamino and bicyclic alkyl amino.
In the context of the invention, term " aryl " refers to monocycle or polycyclic aromatic alkyl.Aryl is generally has 6-24 carbon atom, and preferred 6-20 carbon atom, an especially 6-14 carbon atom is as the aromatic group of ring members.Aryl is preferably phenyl, naphthyl, indenyl, fluorenyl, anthryl, phenanthryl, naphthacenyl, base, pyrenyl, coronenyl, perylene base etc., more preferably phenyl or naphthyl.
The aryl replaced depends on that the number of its member ring systems and size can have one or more (for example 1,2,3,4,5 or be greater than 5) substituting group.These preferably are selected from alkyl, alkoxyl group, alkylthio, cycloalkyl, Heterocyclylalkyl, aryl, heteroaryl, fluorine, chlorine, bromine, hydroxyl, sulfydryl, cyano group, nitro, nitroso-group, formyl radical, acyl group, COOH, carboxylic acid compound group, alkyl carbonyl oxy, formamyl, SO independently of one another 3h, azochlorosulfonate acid compound group, sulfamyl, sulphonamide, amidino groups, NE 5e 6, E wherein 5and E 6be hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl independently of one another.Alkyl on aryl, alkoxyl group, alkylamino, alkylthio, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl substituting group can be again not replace or replace.With reference to the top substituting group that these groups are mentioned.Substituting group on aryl is preferably selected from alkyl, alkoxyl group, haloalkyl, halogenated alkoxy, aryl, fluorine, chlorine, bromine, cyano group and nitro.The aryl replaced is more preferably usually with 1,2,3,4 or 5, preferably 1,2 or 3 substituent substituted-phenyl.
The aryl replaced is preferably the aryl (" alkaryl ", hereinafter also referred to as alkylaryl) replaced by least one alkyl.Alkaryl depends on that the size of aromatic ring system can have one or more (for example 1,2,3,4,5,6,7,8,9 or be greater than 9) alkyl substituent.Alkyl substituent can be not replace or replace.Thus, reference is about the not above-mentioned explanation of replacement and substituted alkyl.In preferred embodiments, alkaryl only has unsubstituted alkyl substituent.Alkaryl is preferably with 1,2,3,4 or 5, and preferably 1,2 or 3, the more preferably phenyl of 1 or 2 alkyl substituent.
Aryl with one or more groups is for example 2-, 3-and 4-aminomethyl phenyl, 2,4-, 2,5-, 3,5-and 2,6-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2-, 3-and 4-ethylphenyl, 2,4-, 2,5-, 3,5-and 2,6-diethyl phenyl, 2,4,6-triethyl phenyl, 2-, 3-and 4-propyl group phenyl, 2,4-, 2,5-, 3,5-and 2,6-dipropyl phenyl, 2,4,6-tripropyl phenyl, 2-, 3-and 4-isopropyl phenyl, 2,4-, 2,5-, 3,5-and 2,6-diisopropyl phenyl, 2,4,6-triisopropyl phenyl, 2-, 3-and 4-butyl phenyl, 2,4-, 2,5-, 3,5-and 2,6-dibutyl phenyl, 2,4,6-tributyl phenyl, 2-, 3-and 4-isobutyl phenenyl, 2,4-, 2,5-, 3,5-and 2,6-diisobutyl phenyl, 2,4,6-triisobutyl phenyl, 2-, 3-and 4-secondary butyl phenenyl, 2,4-, 2,5-, 3,5-and 2,6-di-sec-butyl phenyl, 2,4,6-, tri-secondary butyl phenenyls, 2-, 3-and 4-tert-butyl-phenyl, 2,4-, 2,5-, 3,5-and 2,6-di-tert-butyl-phenyl and 2,4,6-tri-tert phenyl, 2-, 3-and 4-p-methoxy-phenyl, 2,4-, 2,5-, 3,5-and 2, the 6-Dimethoxyphenyl, 2,4,6-trimethoxyphenyl, 2-, 3-and 4-ethoxyl phenenyl, 2,4-, 2,5-, 3,5-and 2,6-diethoxy phenyl, 2,4,6-triethoxy phenyl, 2-, 3-and 4-propoxy-phenyl, 2,4-, 2,5-, 3,5-and 2,6-dipropoxy phenyl, 2-, 3-and 4-isopropyl phenyl, 2,4-, 2,5-, 3,5-and 2,6-diisopropoxy phenyl and 2-, 3-and 4-butoxy phenyl, 2-, 3-and 4-chloro-phenyl-, (the chloro-6-methyl of 2-) phenyl, (the chloro-6-ethyl of 2-) phenyl, (the chloro-6-methyl of 4-) phenyl, (the chloro-6-ethyl of 4-) phenyl.
Above-mentioned explanation about aryl also is applicable to the aryl structure division in aryloxy, arylthio (=artyl sulfo), single arylamino and ammonia diaryl base.
In the context of the invention, statement " Heterocyclylalkyl " comprises usually having 5-8 annular atoms, preferably non-aromatic unsaturated the or complete saturated alicyclic group of 5 or 6 annular atomses.In Heterocyclylalkyl, compare 1,2,3,4 or be greater than 4 ring carbon atoms and substitute by heteroatoms or containing heteroatomic group with corresponding cycloalkyl.Heteroatoms or containing be preferably selected from-O-of heteroatomic group ,-S-,-NR e-,-C (=O)-,-S (=O)-and/or-S (=O) 2-.R ebe preferably hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl.Heterocyclylalkyl is unsubstituted or optionally with one or more, for example 1,2,3,4,5,6 or 7 identical or different group.These preferably are selected from alkyl, alkoxyl group, alkylamino, alkylthio, cycloalkyl, Heterocyclylalkyl, aryl, heteroaryl, fluorine, chlorine, bromine, hydroxyl, sulfydryl, cyano group, nitro, nitroso-group, formyl radical, acyl group, COOH, carboxylic acid compound group, alkyl carbonyl oxy, formamyl, SO independently of one another 3h, azochlorosulfonate acid compound group, sulfamyl, sulphonamide, amidino groups, NE 5e 6, E wherein 5and E 6be hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl independently of one another.The example of Heterocyclylalkyl is pyrrolidyl, piperidyl, 2,2,6 especially, 6-tetramethyl-piperidyl, imidazolidyl, pyrazolidyl,
Figure BDA00003115671900172
oxazolidinyl, morpholinyl, thiazolidyl, isothiazole alkyl, different
Figure BDA00003115671900171
oxazolidinyl, piperazinyl, tetrahydro-thienyl, dihydro-thiophene-2-base, tetrahydrofuran base, dihydrofuran-2-base, THP trtrahydropyranyl, 2-
Figure BDA00003115671900181
azoles quinoline base, 3-
Figure BDA00003115671900182
azoles quinoline base, 4-
Figure BDA00003115671900183
azoles quinoline base and two
Figure BDA00003115671900184
alkyl.
The Heterocyclylalkyl replaced depends on that ring size can have one or more (for example 1,2,3,4,5 or be greater than 5) substituting group.These preferably are selected from alkyl, alkoxyl group, alkylthio, cycloalkyl, Heterocyclylalkyl, aryl, heteroaryl, fluorine, chlorine, bromine, hydroxyl, sulfydryl, cyano group, nitro, nitroso-group, formyl radical, acyl group, COOH, carboxylic acid compound group, alkyl carbonyl oxy, formamyl, SO independently of one another 3h, azochlorosulfonate acid compound group, sulfamyl, sulphonamide, amidino groups, NE 7e 8, E wherein 7and E 8be hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl independently of one another.In the situation that replace, Heterocyclylalkyl is preferably with one or more, for example 1,2,3,4 or 5 C 1-C 6alkyl.
Above-mentioned explanation about Heterocyclylalkyl also is applicable to the Heterocyclylalkyl structure division in heterocycle alkoxyl group, heterocycle alkylthio (=Heterocyclylalkyl sulfenyl), single Heterocyclylalkyl amino and two Heterocyclylalkyl amino.
In the context of the invention, statement " heteroaryl " comprises monocycle or encircles heteroaromatic group more.Except ring carbon atom, these have 1,2,3,4 or be greater than 4 heteroatomss as ring members.Heteroatoms is preferably selected from oxygen, nitrogen, selenium and sulphur.Heteroaryl preferably has 5-18, for example 5,6,8,9,10,11,12,13 or 14 annular atomses.
Bicyclic heteroaryl is preferably 5 or 6 Yuans heteroaryls, as different as 2-furyl (furans-2-yl), 3-furyl (furans-3-yl), 2-thienyl (thiophene-2-yl), 3-thienyl (thiene-3-yl-), selenophen-2-base, selenophen-3-base, 1H-pyrroles-2-base, 1H-pyrroles-3-base, pyrroles-1-base, imidazoles-2-base, imidazoles-1-base, imidazol-4 yl, pyrazol-1-yl, pyrazole-3-yl, pyrazoles-4-base, pyrazoles-5-base, 3-
Figure BDA00003115671900185
azoles base, 4-are different
Figure BDA00003115671900186
azoles base, 5-are different
Figure BDA00003115671900187
azoles base, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-
Figure BDA00003115671900188
azoles base, 4-
Figure BDA00003115671900189
azoles base, 5-
Figure BDA000031156719001810
azoles base, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 1,2,4- diazole-3-base, 1,2,4-
Figure BDA000031156719001812
diazole-5-base, 1,3,4-
Figure BDA000031156719001813
diazole-2-base, 1,2,4-thiadiazoles-3-base, 1,2,4-thiadiazoles-5-base, 1,3,4-thiadiazoles-2-base, 4H-[1,2,4]-triazole-3-base, 1,3,4-triazole-2-base, 1,2,3-triazoles-1-base, 1,2,4-triazol-1-yl, pyridine-2-base, pyridin-3-yl, pyridin-4-yl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 2-pyrazinyl, 1,3,5-triazine-2-base and 1,2,4-triazine-3-base.
Polyheteroaromatic has 2,3,4 or more than 4 fused rings.The ring condensed can be aromatics, saturated or part undersaturated.The example of polyheteroaromatic is quinolyl, isoquinolyl, indyl, pseudoindolyl, indolizine base, benzofuryl, isobenzofuran-base, benzothienyl, benzo
Figure BDA00003115671900191
azoles base, benzisoxa
Figure BDA00003115671900192
azoles base, benzothiazolyl, benzo di azoly, diazosulfide base, benzo
Figure BDA00003115671900194
piperazine base, benzopyrazoles base, benzimidazolyl-, benzotriazole base, phentriazine base, benzo selenophen base, thienothiophene base, Thienopyrimidine base, thiazole benzothiazolyl, dibenzopyrrole base (carbazyl), dibenzofuran group, dibenzothiophene base, naphtho-[2,3-b] thienyl, naphtho-[2,3-b] furyl, indolinyl, dihydro indolizine base, dihydro pseudoindolyl, dihydroquinoline base and dihydro-isoquinoline base.
The heteroaryl replaced depends on that the number of its member ring systems and size can have one or more (for example 1,2,3,4,5 or be greater than 5) substituting group.These preferably are selected from alkyl, alkoxyl group, alkylthio, cycloalkyl, Heterocyclylalkyl, aryl, heteroaryl, fluorine, chlorine, bromine, hydroxyl, sulfydryl, cyano group, nitro, nitroso-group, formyl radical, acyl group, COOH, carboxylic acid compound group, alkyl carbonyl oxy, formamyl, SO independently of one another 3h, azochlorosulfonate acid compound group, sulfamyl, sulphonamide, amidino groups, NE 9e 10, E wherein 9and E 10be hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl or heteroaryl independently of one another.Halogenic substituent is preferably fluorine, chlorine or bromine.Substituting group is preferably selected from C 1-C 6alkyl, C 1-C 6alkoxyl group, hydroxyl, carboxyl, halogen and cyano group.
Above-mentioned explanation about heteroaryl also is applicable to the heteroaryl structure division in heteroaryloxy, heteroarylthio, single heteroaryl amino and two heteroaryl aminos.
Preferably, in the compound of general formula (I), the group M of containing metal atom comprises the metal that is selected from periodictable the 4th, 5,6,7,8,9,10,11,12 and 13 families.Preferred metal is Ti, Zr, Cr, Mo, W, Re, Fe, Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag, Au, Zn, In and B.
The compound of following general formula (I) particularly preferably, wherein M is the group containing Pd (II), Pt (II) or Au (I).
Suitable group M is formula L in principle ythe group of Me-, wherein Me is metal, L is that part and y depend on the valence state of metal and type and the coordination positional number purpose integer occupied by each ligand L.Suitable ligand L is independently selected from F, Cl, Br, I, CO, isonitrile, nitrile, amine, carboxylicesters, acetylacetonate, hydride, alkene, cycloolefin, diolefine, alkynes, C 5h 5 -, C 7h 7 +, containing N heterocycle, aromatic hydrocarbon, heteroaromatic hydrocarbon, ether, PF 3, phosphurane class (phospholes), phosphabenzene, phosphine class (P (C for example 6h 5) 3, P (CH 3) (C 6h 5) 2, P (CH 3) 2(C 6h 5), P (CH 3) 3, dppe (ethylene two [(phenylbenzene) phosphine]), P (C 6h 11) 3deng), phosphinate (phosphinite), phosphinate, phosphorous acid ester, alkyl sulfonic ester, aromatic yl sulphonate etc.
In the compound of general formula (I), M especially is selected from PdCl 2(CNR 1), PtCl 2(CNR 1), PdCl (CNR 1) 2, Au (CNR 1) and AuCl, wherein R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl.
R 1be preferably selected from the group of formula IV.1-IV.5, particularly preferably the group of formula IV.1 and IV.2:
Wherein
# means the bonding position with nitrogen-atoms,
P is 0 or 1,
X is 2 or 3, wherein when x is 2, with radicals R icarbon atom additionally with 1 hydrogen atom,
X in formula IV.2, IV.3 and IV.4 1be 0,1,2,3,4 or 5,
X in formula IV.2, IV.3 and IV.4 2be 0 or 1,
Condition is x in formula IV.2, IV.3 and IV.4 1and x 2summation be 0,1,2,3,4 or 5,
X in formula IV.5 1be 0,1 or 2,
X in formula IV.5 2be 0 or 1,
Condition is x in formula IV.5 1and x 2summation be 0,1 or 2,
A when existing, be can by one or more being selected from-O-and-C at the non-adjacent group interval of S- 1-C 10alkylidene group,
Radicals R ibe selected from independently of one another C 1-C 30alkyl, C 1-C 30alkoxyl group or C 1-C 30alkylthio, wherein the alkyl chain in alkyl, alkoxyl group or alkylthio can be by one or more non-adjacent Sauerstoffatom intervals.
More preferably in formula IV.2, IV.3 and IV.4, x 1be 0,1,2 or 3, x 2be 0 or 1, condition is x 1and x 2summation be 0,1,2 or 3.
More preferably R 1be selected from C 1-C 6alkyl, phenyl and with 1,2 or 3 independently selected from C 1-C 6the phenyl of the group of alkyl and chlorine.R 1especially be selected from sec.-propyl, the tertiary butyl, the 2-aminomethyl phenyl, the 3-aminomethyl phenyl, the 4-aminomethyl phenyl, 2, the 4-3,5-dimethylphenyl, 2, the 5-3,5-dimethylphenyl, 3, the 5-3,5-dimethylphenyl, 2, the 6-3,5-dimethylphenyl, 2, 4, the 6-trimethylphenyl, the 2-ethylphenyl, the 3-ethylphenyl, the 4-ethylphenyl, 2, 4-diethyl phenyl, 2, 5-diethyl phenyl, 3, 5-diethyl phenyl, 2, 6-diethyl phenyl, 2, 4, 6-triethyl phenyl, 2-propyl group phenyl, 3-propyl group phenyl, 4-propyl group phenyl, 2, 4-dipropyl phenyl, 2, 5-dipropyl phenyl, 3, 5-dipropyl phenyl, 2, 6-dipropyl phenyl, 2, 4, 6-tripropyl phenyl, the 2-isopropyl phenyl, the 3-isopropyl phenyl, the 4-isopropyl phenyl, 2, 4-diisopropyl phenyl 2, the 5-diisopropyl phenyl, 3, the 5-diisopropyl phenyl, 2, the 6-diisopropyl phenyl, 2, 4, 6-triisopropyl phenyl, the 2-butyl phenyl, the 3-butyl phenyl, the 4-butyl phenyl, 2, 4-dibutyl phenyl, 2, 5-dibutyl phenyl, 3, 5-dibutyl phenyl, 2, 6-dibutyl phenyl, 2, 4, 6-tributyl phenyl, the 2-isobutyl phenenyl, the 3-isobutyl phenenyl, the 4-isobutyl phenenyl, 2, 4-diisobutyl phenyl, 2, 5-diisobutyl phenyl, 3, 5-diisobutyl phenyl, 2, 6-diisobutyl phenyl, 2, 4, 6-triisobutyl phenyl, the 2-secondary butyl phenenyl, the 3-secondary butyl phenenyl, the 4-secondary butyl phenenyl, 2, 4-di-sec-butyl phenyl, 2, 5-di-sec-butyl phenyl, 3, 5-di-sec-butyl phenyl, 2, 6-di-sec-butyl phenyl, 2, 4, 6-tri-secondary butyl phenenyls, the 2-tert-butyl-phenyl, the 3-tert-butyl-phenyl, the 4-tert-butyl-phenyl, 2, the 4-di-tert-butyl-phenyl, 2, the 5-di-tert-butyl-phenyl, 3, the 5-di-tert-butyl-phenyl, 2, the 6-di-tert-butyl-phenyl, 2, 4, 6-tri-tert phenyl, the 2-chloro-phenyl-, the 3-chloro-phenyl-, the 4-chloro-phenyl-, (the chloro-6-methyl of 2-) phenyl, (the chloro-6-ethyl of 2-) phenyl, (the chloro-6-propyl group of 2-) phenyl, (the chloro-6-sec.-propyl of 2-) phenyl, (the chloro-6-butyl of 2-) phenyl, (the chloro-6-isobutyl-of 2-) phenyl, (the chloro-6-sec-butyl of 2-) phenyl and (the chloro-6-tertiary butyl of 2-) phenyl.
R 1especially be selected from the tertiary butyl, 2,6-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropyl phenyl and (the chloro-6-methyl of 2-) phenyl.
Preferred R 2be selected from hydrogen, alkyl and cycloalkyl, especially C 1-C 6alkyl, phenyl-C 1-C 6alkyl and C 5-C 15cycloalkyl.
More preferably R 2be selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, 1-phenylethyl, cyclopentyl, cyclohexyl, cyclo-dodecyl, cyclopentadecane base and 1-adamantyl.
According to the first preferred embodiment, R 3and R 4independently selected from hydrogen with the aryl that does not replace or replace.If residue R 3and R 4in at least one is aryl, this residue is preferably phenyl.R 3and R 4especially be hydrogen.
According to the second preferred embodiment, R 3and R 4with together with the carbon atom of their institute's bondings, be C=O.
According to the 3rd preferred embodiment, R 3for group O-R 3a, R wherein 3afor the group via carbon atom, Siliciumatom, sulphur atom, phosphorus atom, boron atom or titanium atom and oxygen bonding.In this embodiment, for the compound of the general formula (I) that wherein n is 0, residue R 4and R 7mean to be equal to R 4and R 7carbon atom between the key of two keys.In this embodiment, for the compound of the general formula (I) that wherein n is 1, residue R 4and R 5mean to be equal to R 4and R 5carbon atom between the key of two keys.
Preferred R 3abe selected from the group of formula V-A, V-B, V-C, V-D, V-E, V-F, V-G, V-H, V-I, V-K or V-L, the more preferably group of formula V-A, V-B or V-C,
Figure BDA00003115671900221
Wherein
# means the bonding position with Sauerstoffatom,
Be selected from-O-of T and-NR vf, R wherein vffor hydrogen, alkyl, cycloalkyl or aryl,
R va, R vbbe selected from the alkyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vc, R vd, R vebe selected from independently of each other the alkyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vgbe selected from the Heterocyclylalkyl that does not replace or replace,
R vhbe selected from the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R viand R vkbe selected from independently of each other the alkyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace, alkoxyl group, the aryloxy that does not replace or replace and the cycloalkyloxy that does not replace or replace,
R vmand R vnbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R voand R vpbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vq, R vrand R vsbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vt, R vuand R vvbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace, and
R vw, R vxand R vybe selected from independently of each other the alkoxyl group that does not replace or replace, the alkenyloxy that does not replace or replace, the cycloalkyloxy that does not replace or replace and the aryloxy that does not replace or replace; And
D +for the positively charged ion Equivalent.
Positively charged ion Equivalent D +only as counter ion and can freely be selected from monovalent cation and corresponding to the polyvalent cation part of single positive charge.Suitable positively charged ion is for example alkalimetal ion D +, Na for example +and K +, alkaline earth metal cation, for example Ca 2+, ammonium ion.
Preferred R vafor phenyl, its be not substituted or by 1,2 or 3 independently selected from C 1-C 4alkyl, C 1-C 4the group of alkoxyl group and nitro replaces.
R vbbe preferably (C 1-C 4alkyl) phenyl, wherein (C 1-C 4alkyl) the phenyl structure division of phenyl be not substituted or by 1,2 or 3 independently selected from C 1-C 4alkyl, C 1-C 4the group of alkoxyl group and nitro replaces.
Preferably T is-O-.In the group of formula V-B, be preferably-O-of T and R vbfor benzyl, wherein the phenyl structure division of benzyl be not substituted or by 1,2 or 3 independently selected from C 1-C 4alkyl, C 1-C 4the group of alkoxyl group and nitro replaces.
Preferred R vc, R vdand R vebe selected from independently of each other C 1-C 6alkyl, C 5-C 10cycloalkyl and be not substituted or by 1,2 or 3 independently selected from C 1-C 4alkyl and C 1-C 4the phenyl that the group of alkoxyl group replaces.The example of group V-C is trimethyl silyl, triethylsilyl, triisopropyl silyl, dimethyl sec.-propyl silyl, diethyl sec.-propyl silyl, dimethyl hexyl silyl, 2-norcamphyl dimetylsilyl, t-butyldimethylsilyl, di-t-butyl methyl-silicane base, t-butyldiphenylsilyl, tribenzyl silyl, triphenyl silyl and diphenyl methyl silyl.
The group of preferred formula V-D is 2,2,5,5-tetramethylpyrrolidi-e-3-ketone-1--sulfinic acid ester.
Preferred R vhfor C 1-C 4alkyl, C 1-C 4haloalkyl, the C be substituted by phenyl 1-C 4alkyl, wherein phenyl be not substituted or by 1,2 or 3 independently selected from C 1-C 4alkyl, C 1-C 4alkoxyl group, C 1-C 4haloalkyl, C 1-C 4the group of halogenated alkoxy and nitro replaces, C 2-C 6alkenyl, benzyl, phenyl, wherein phenyl be not substituted or by 1,2 or 3 independently selected from C 1-C 4alkyl, C 1-C 4haloalkyl, C 1-C 4halogenated alkoxy, C 1-C 4the group of alkoxyl group and nitro replaces.The group example of formula V-E is methane sulfonate, trifluoromethayl sulfonic acid ester, 2-[(4-nitrophenyl) ethyl] sulphonate, allyl sulphonic acid ester, benzyl sulphonate, tosylate and 2-trifluoromethyl benzene sulfonate.
Preferred R viand R vkbe selected from independently of each other C 1-C 6alkyl, C 1-C 6alkoxyl group and be not substituted or by 1,2 or 3 independently selected from C 1-C 4alkyl, C 1-C 4haloalkyl, C 1-C 4halogenated alkoxy and C 1-C 4the phenyl that the group of alkoxyl group replaces.
Preferred R 7, R 8and if the words R existed 5and R 6independently selected from hydrogen with the aryl that does not replace or replace.If residue R 7, R 8and if the words R existed 5and R 6in at least one is aryl, this residue is preferably phenyl.In the first preferred embodiment, R 7, R 8and if the words R existed 5and R 6be all hydrogen.In the second preferred embodiment, be selected from R 7, R 8and if the words R existed 5and R 6in one of residue be that phenyl and other residues are all hydrogen.
In particular embodiments, two radicals R 2and R 8can also and R 2n atom and the R of institute's bonding 8the carbon atom of institute's bonding forms 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, 11-or 12 Yuans nitrogen heterocyclics that do not replace or replace together, and this heterocycle can optionally have 1,2 or 3 independently selected from O, N, NR awith the heteroatoms of S or containing heteroatom group as ring members, R wherein afor hydrogen, alkyl, cycloalkyl or aryl.Suitable substituent on this 3-12 person's nitrogen heterocyclic is preferably halogen, cyano group, nitro, hydroxyl, sulfydryl, amino, carboxyl, C 1-C 6alkyl, C 1-C 6alkoxyl group, C 2-C 6alkenyloxy, C 2-C 6alkynyloxy group, C 1-C 6halogenated alkoxy and C 1-C 6alkylthio and/or form fused benzene rings with two substituting groups of the adjacent atom bonding of this 3-12 element heterocycle together with described atom, condense naphthalene nucleus, condense saturated or unsaturated 5,6 or 7 Yuans carbocyclic rings of part or contain 1,2,3 or 4 and be selected from oxygen, sulphur and NR aheteroatoms as 5,6 or 7 element heterocycle, the wherein R that condense of ring members aas defined above, and wherein this fused rings is not substituted or can be selected from halogen, cyano group, nitro, hydroxyl, sulfydryl, amino, carboxyl, C with 1,2,3 or 4 1-C 6alkyl, C 1-C 6alkoxyl group, C 2-C 6alkenyloxy, C 2-C 6alkynyloxy group, C 1-C 6halogenated alkoxy and C 1-C 6any combination of the group of alkylthio.
The compound of preferred formula (I-D):
Figure BDA00003115671900251
Wherein n, M, R 1, R 3, R 4, R 5and R 6there is above-mentioned implication, especially as the implication of preferably mentioning.Particularly, n is that 0, M is selected from PdCl 2(CNR 1), PdCl (CNR 1) 2, PtCl 2(CNR 1), Au (CNR 1) and AuCl, R 1be selected from the tertiary butyl, 2,6-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropyl phenyl and (the chloro-6-methyl of 2-) phenyl and R 3and R 4be hydrogen.
In above-mentioned the first scheme, the inventive method is for the preparation of formula (I-A.1) or compound (I-A.2):
Figure BDA00003115671900252
Wherein
M, R 1, R 2, R 5, R 6, R 7and R 8there is above-mentioned implication, especially as the implication of preferably mentioning,
R 3and R 4independently selected from hydrogen and the alkyl that do not replace or replace in each case, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, the heterocycle alkoxyl group, the heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino.
In the preferred embodiment of this first scheme, the inventive method is for the preparation of the compound of general formula (I-A.2.1):
Wherein M, R 1, R 2, R 3and R 7there is above-mentioned implication, especially as the implication of preferably mentioning.
(in formula I-A.2.1, residue R 4and R 8for hydrogen and not shown.)
The compound of general formula shown in following table 1-5 (I-A.2.2) itself has represented the preferred embodiments of the invention.R shown in lower Table A 1, R 2and R 3implication mean equally independently of each other and the embodiment of the present invention of combinatorial optimization especially.
Figure BDA00003115671900262
Table 1
Wherein group M is PdCl 2(CNR 1) and R 1, R 2and R 3combination for compound in each case corresponding to formula (I-A.2.2) compound of a line of Table A.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl 2(CNR 1) in residue R 1there is identical meanings.With general formula (I), compare, in formula (I-A.2.2), n is 0 and residue R 4, R 7and R 8for hydrogen and not shown.
Table 2
Wherein group M is PtCl 2(CNR 1) and R 1, R 2and R 3combination for compound in each case corresponding to formula (I-A.2.2) compound of a line of Table A.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PtCl 2(CNR 1) in residue R 1all there is identical meanings.
Table 3
Wherein group M is PdCl (CNR 1) 2and R 1, R 2and R 3combination for compound in each case corresponding to formula (I-A.2.2) compound of a line of Table A.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl (CNR 1) 2in residue R 1all there is identical meanings.
Table 4
Wherein group M is AuCl and R 1, R 2and R 3combination for compound in each case corresponding to formula (I-A.2.2) compound of a line of Table A.
Table 5
Wherein group M is Au (CNR 1) and R 1, R 2and R 3combination for compound in each case corresponding to formula (I-A.2.2) compound of a line of Table A.Residue R with the theheterocyclic nitrogen atom bonding 1with at group AuCl (CNR 1) in residue R 1all there is identical meanings.
Table A
Sequence number R 1 R 2 R 3
A-1 2,6-3,5-dimethylphenyl Methyl H
A-2 2,6-3,5-dimethylphenyl Ethyl H
A-3 2,6-3,5-dimethylphenyl N-propyl H
A-4 2,6-3,5-dimethylphenyl Sec.-propyl H
A-5 2,6-3,5-dimethylphenyl Butyl H
A-6 2,6-3,5-dimethylphenyl Isobutyl- H
A-7 2,6-3,5-dimethylphenyl Sec-butyl H
A-8 2,6-3,5-dimethylphenyl The tertiary butyl H
A-9 2,6-3,5-dimethylphenyl Cyclohexyl H
A-10 2,6-3,5-dimethylphenyl The 1-adamantyl H
A-11 2,6-3,5-dimethylphenyl Methyl Phenyl
A-12 2,6-3,5-dimethylphenyl Ethyl Phenyl
A-13 2,6-3,5-dimethylphenyl N-propyl Phenyl
A-14 2,6-3,5-dimethylphenyl Sec.-propyl Phenyl
A-15 2,6-3,5-dimethylphenyl Butyl Phenyl
A-16 2,6-3,5-dimethylphenyl Isobutyl- Phenyl
A-17 2,6-3,5-dimethylphenyl Sec-butyl Phenyl
A-18 2,6-3,5-dimethylphenyl The tertiary butyl Phenyl
A-19 2,6-3,5-dimethylphenyl Cyclohexyl Phenyl
A-20 2,6-3,5-dimethylphenyl The 1-adamantyl Phenyl
A-21 2,4,6-trimethylphenyl Methyl H
A-22 2,4,6-trimethylphenyl Ethyl H
A-23 2,4,6-trimethylphenyl N-propyl H
A-24 2,4,6-trimethylphenyl Sec.-propyl H
A-25 2,4,6-trimethylphenyl Butyl H
A-26 2,4,6-trimethylphenyl Isobutyl- H
A-27 2,4,6-trimethylphenyl Sec-butyl H
A-28 2,4,6-trimethylphenyl The tertiary butyl H
A-29 2,4,6-trimethylphenyl Cyclohexyl H
Sequence number R 1 R 2 R 3
A-30 2,4,6-trimethylphenyl The 1-adamantyl H
A-31 2,4,6-trimethylphenyl Methyl Phenyl
A-32 2,4,6-trimethylphenyl Ethyl Phenyl
A-33 2,4,6-trimethylphenyl N-propyl Phenyl
A-34 2,4,6-trimethylphenyl Sec.-propyl Phenyl
A-35 2,4,6-trimethylphenyl Normal-butyl Phenyl
A-36 2,4,6-trimethylphenyl Isobutyl- Phenyl
A-37 2,4,6-trimethylphenyl Sec-butyl Phenyl
A-38 2,4,6-trimethylphenyl The tertiary butyl Phenyl
A-39 2,4,6-trimethylphenyl Cyclohexyl Phenyl
A-40 2,4,6-trimethylphenyl The 1-adamantyl Phenyl
A-41 2,6-diisopropyl phenyl Methyl H
A-42 2,6-diisopropyl phenyl Ethyl H
A-43 2,6-diisopropyl phenyl N-propyl H
A-44 2,6-diisopropyl phenyl Sec.-propyl H
A-45 2,6-diisopropyl phenyl Normal-butyl H
A-46 2,6-diisopropyl phenyl Isobutyl- H
A-47 2,6-diisopropyl phenyl Sec-butyl H
A-48 2,6-diisopropyl phenyl The tertiary butyl H
A-49 2,6-diisopropyl phenyl Cyclohexyl H
A-50 2,6-diisopropyl phenyl The 1-adamantyl H
A-51 2,6-diisopropyl phenyl Methyl Phenyl
A-52 2,6-diisopropyl phenyl Ethyl Phenyl
A-53 2,6-diisopropyl phenyl N-propyl Phenyl
A-54 2,6-diisopropyl phenyl Sec.-propyl Phenyl
A-55 2,6-diisopropyl phenyl Normal-butyl Phenyl
A-56 2,6-diisopropyl phenyl Isobutyl- Phenyl
A-57 2,6-diisopropyl phenyl Sec-butyl Phenyl
A-58 2,6-diisopropyl phenyl The tertiary butyl Phenyl
A-59 2,6-diisopropyl phenyl Cyclohexyl Phenyl
A-60 2,6-diisopropyl phenyl The 1-adamantyl Phenyl
A-61 (the chloro-6-methyl of 2-) phenyl Methyl H
A-62 (the chloro-6-methyl of 2-) phenyl Ethyl H
A-63 (the chloro-6-methyl of 2-) phenyl N-propyl H
A-64 (the chloro-6-methyl of 2-) phenyl Sec.-propyl H
A-65 (the chloro-6-methyl of 2-) phenyl Normal-butyl H
A-66 (the chloro-6-methyl of 2-) phenyl Isobutyl- H
Sequence number R 1 R 2 R 3
A-67 (the chloro-6-methyl of 2-) phenyl Sec-butyl H
A-68 (the chloro-6-methyl of 2-) phenyl The tertiary butyl H
A-69 (the chloro-6-methyl of 2-) phenyl Cyclohexyl H
A-70 (the chloro-6-methyl of 2-) phenyl The 1-adamantyl H
A-71 (the chloro-6-methyl of 2-) phenyl Methyl Phenyl
A-72 (the chloro-6-methyl of 2-) phenyl Ethyl Phenyl
A-73 (the chloro-6-methyl of 2-) phenyl N-propyl Phenyl
A-74 (the chloro-6-methyl of 2-) phenyl Sec.-propyl Phenyl
A-75 (the chloro-6-methyl of 2-) phenyl Normal-butyl Phenyl
A-76 (the chloro-6-methyl of 2-) phenyl Isobutyl- Phenyl
A-77 (the chloro-6-methyl of 2-) phenyl Sec-butyl Phenyl
A-78 (the chloro-6-methyl of 2-) phenyl The tertiary butyl Phenyl
A-79 (the chloro-6-methyl of 2-) phenyl Cyclohexyl Phenyl
A-80 (the chloro-6-methyl of 2-) phenyl The 1-adamantyl Phenyl
A-81 The tertiary butyl Methyl H
A-82 The tertiary butyl Ethyl H
A-83 The tertiary butyl N-propyl H
A-84 The tertiary butyl Sec.-propyl H
A-85 The tertiary butyl Normal-butyl H
A-86 The tertiary butyl Isobutyl- H
A-87 The tertiary butyl Sec-butyl H
A-88 The tertiary butyl The tertiary butyl H
A-89 The tertiary butyl Cyclohexyl H
A-90 The tertiary butyl The 1-adamantyl H
A-91 The tertiary butyl Methyl Phenyl
A-92 The tertiary butyl Ethyl Phenyl
A-93 The tertiary butyl N-propyl Phenyl
A-94 The tertiary butyl Sec.-propyl Phenyl
A-95 The tertiary butyl Normal-butyl Phenyl
A-96 The tertiary butyl Isobutyl- Phenyl
A-97 The tertiary butyl Sec-butyl Phenyl
A-98 The tertiary butyl The tertiary butyl Phenyl
A-99 The tertiary butyl Cyclohexyl Phenyl
A-100 The tertiary butyl The 1-adamantyl Phenyl
In the preferred embodiment of above-mentioned alternative plan, the inventive method is for the preparation of general formula (I-B.1) or compound (I-B.2):
Figure BDA00003115671900301
Wherein M, R 1, R 2, R 5, R 6, R 7and R 8there is above-mentioned implication, especially as the implication of preferably mentioning.
In the especially preferred embodiment of this alternative plan, the inventive method is for the preparation of the compound of general formula (I-B.2.1):
Figure BDA00003115671900302
Wherein M, R 1and R 2there is above-mentioned implication, especially as the implication of preferably mentioning.
The compound of general formula shown in following table 6-10 (I-B.2.1) itself has represented the preferred embodiments of the invention.R shown in following table B 1and R 2implication mean equally independently of each other and the embodiment of the present invention of combinatorial optimization especially.
Table 6
Wherein group M is PdCl 2(CNR 1) and R 1and R 2combination for compound in each case corresponding to formula (I-B.2.1) compound of a line of table B.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl 2(CNR 1) in residue R 1there is identical meanings.With general formula (I), compare, in formula (I-B.2.1), n is 0 and residue R 7and R 8for hydrogen and not shown.
Table 7
Wherein group M is PtCl 2(CNR 1) and R 1and R 2combination for compound in each case corresponding to formula (I-B.2.1) compound of a line of table B.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PtCl 2(CNR 1) in residue R 1all there is identical meanings.
Table 8
Wherein group M is PdCl (CNR 1) 2and R 1, R 2and R 3combination for compound in each case corresponding to formula (I-B.2.1) compound of a line of table B.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl (CNR 1) 2in residue R 1all there is identical meanings.
Table 9
Wherein group M is AuCl and R 1and R 2combination for compound in each case corresponding to formula (I-B.2.1) compound of a line of table B.
Table 10
Wherein group M is Au (CNR 1) and R 1and R 2combination for compound in each case corresponding to formula (I-B.2.1) compound of a line of table B.Residue R with the theheterocyclic nitrogen atom bonding 1with at group AuCl (CNR 1) in residue R 1all there is identical meanings.
Table B
Sequence number R 1 R 2
B-1 2,6-3,5-dimethylphenyl Sec.-propyl
B-2 2,6-3,5-dimethylphenyl The tertiary butyl
B-3 2,6-3,5-dimethylphenyl Cyclohexyl
B-4 2,6-3,5-dimethylphenyl Cyclo-dodecyl
B-5 2,6-3,5-dimethylphenyl The 1-adamantyl
B-6 2,6-3,5-dimethylphenyl The 1-phenylethyl
B-7 2,4,6-trimethylphenyl Sec.-propyl
B-8 2,4,6-trimethylphenyl The tertiary butyl
B-9 2,4,6-trimethylphenyl Cyclohexyl
B-10 2,4,6-trimethylphenyl Cyclo-dodecyl
B-11 2,4,6-trimethylphenyl The 1-adamantyl
B-12 2,4,6-trimethylphenyl The 1-phenylethyl
B-13 2,6-diisopropyl phenyl Sec.-propyl
B-14 2,6-diisopropyl phenyl The tertiary butyl
B-15 2,6-diisopropyl phenyl Cyclohexyl
B-16 2,6-diisopropyl phenyl Cyclo-dodecyl
B-17 2,6-diisopropyl phenyl The 1-adamantyl
B-18 2,6-diisopropyl phenyl The 1-phenylethyl
B-19 (the chloro-6-methyl of 2-) phenyl Sec.-propyl
B-20 (the chloro-6-methyl of 2-) phenyl The tertiary butyl
B-21 (the chloro-6-methyl of 2-) phenyl Cyclohexyl
B-22 (the chloro-6-methyl of 2-) phenyl Cyclo-dodecyl
B-23 (the chloro-6-methyl of 2-) phenyl The 1-adamantyl
B-24 (the chloro-6-methyl of 2-) phenyl The 1-phenylethyl
B-25 The tertiary butyl Sec.-propyl
B-26 The tertiary butyl The tertiary butyl
Sequence number R 1 R 2
B-27 The tertiary butyl Cyclohexyl
B-28 The tertiary butyl Cyclo-dodecyl
B-29 The tertiary butyl The 1-adamantyl
B-30 The tertiary butyl The 1-phenylethyl
In the preferred embodiment of this third party's case, the inventive method is for the preparation of general formula (I-C.1) or compound (I-C.2):
Figure BDA00003115671900321
Wherein M, R 1, R 2, R 3a, R 6, R 7and R 8there is above-mentioned implication, especially as the implication of preferably mentioning.
In the especially preferred embodiment of this third party's case, the inventive method is for the preparation of the compound of general formula (I-C.2.1):
Figure BDA00003115671900322
Wherein M, R 1, R 2and R 3athere is above-mentioned implication, especially as the implication of preferably mentioning.
The compound of general formula shown in following table 11-15 (I-C.2.1) itself represents the preferred embodiments of the invention.R shown in following table C 1, R 2and R 3aimplication mean equally independently of each other and the embodiment of the present invention of combinatorial optimization especially.
Table 10
Wherein group M is PdCl 2(CNR 1) and R 1, R 2and R 3acombination for compound in each case corresponding to formula (I-C.2.1) compound of a line of table C.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl 2(CNR 1) in residue R 1all there is identical meanings.With general formula (I), compare, in formula (I-C.2.1), n is 0 and residue R 8for hydrogen and not shown.
Table 11
Wherein group M is PtCl 2(CNR 1) and R 1, R 2and R 3acombination for compound in each case corresponding to formula (I-C.2.1) compound of a line of table C.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PtCl 2(CNR 1) in residue R 1all there is identical meanings.
Table 12
Wherein group M is PdCl (CNR 1) 2and R 1, R 2and R 3combination for compound in each case corresponding to formula (I-C.2.1) compound of a line of table C.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl (CNR 1) 2in residue R 1all there is identical meanings.
Table 14
Wherein group M is AuCl and R 1, R 2and R 3acombination for compound in each case corresponding to formula (I-C.2.1) compound of a line of table C.
Table 15
Wherein group M is Au (CNR 1) and R 1, R 2and R 3acombination for compound in each case corresponding to formula (I-C.2.1) compound of a line of table C.Residue R with the theheterocyclic nitrogen atom bonding 1with at group Au (CNR 1) in residue R 1all there is identical meanings.
Table C
Sequence number R 1 R 2 R 3a
C-1 2,6-3,5-dimethylphenyl Sec.-propyl T-butyldiphenylsilyl
C-2 2,6-3,5-dimethylphenyl The tertiary butyl T-butyldiphenylsilyl
C-3 2,6-3,5-dimethylphenyl Cyclohexyl T-butyldiphenylsilyl
C-4 2,6-3,5-dimethylphenyl Cyclo-dodecyl T-butyldiphenylsilyl
C-5 2,6-3,5-dimethylphenyl The 1-adamantyl T-butyldiphenylsilyl
C-6 2,6-3,5-dimethylphenyl The 1-phenylethyl T-butyldiphenylsilyl
C-7 2,6-3,5-dimethylphenyl Sec.-propyl Benzoyl
C-8 2,6-3,5-dimethylphenyl The tertiary butyl Benzoyl
C-9 2,6-3,5-dimethylphenyl Cyclohexyl Benzoyl
C-10 2,6-3,5-dimethylphenyl Cyclo-dodecyl Benzoyl
C-11 2,6-3,5-dimethylphenyl The 1-adamantyl Benzoyl
C-12 2,6-3,5-dimethylphenyl The 1-phenylethyl Benzoyl
C-13 2,6-3,5-dimethylphenyl Sec.-propyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-14 2,6-3,5-dimethylphenyl The tertiary butyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-15 2,6-3,5-dimethylphenyl Cyclohexyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-16 2,6-3,5-dimethylphenyl Cyclo-dodecyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-17 2,6-3,5-dimethylphenyl The 1-adamantyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-18 2,6-3,5-dimethylphenyl The 1-phenylethyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
Sequence number R 1 R 2 R 3a
C-19 2,6-diisopropyl phenyl Sec.-propyl T-butyldiphenylsilyl
C-20 2,6-diisopropyl phenyl The tertiary butyl T-butyldiphenylsilyl
C-21 2,6-diisopropyl phenyl Cyclohexyl T-butyldiphenylsilyl
C-22 2,6-diisopropyl phenyl Cyclo-dodecyl T-butyldiphenylsilyl
C-23 2,6-diisopropyl phenyl The 1-adamantyl T-butyldiphenylsilyl
C-24 2,6-diisopropyl phenyl The 1-phenylethyl T-butyldiphenylsilyl
C-25 2,6-diisopropyl phenyl Sec.-propyl Benzoyl
C-26 2,6-diisopropyl phenyl The tertiary butyl Benzoyl
C-27 2,6-diisopropyl phenyl Cyclohexyl Benzoyl
C-28 2,6-diisopropyl phenyl Cyclo-dodecyl Benzoyl
C-29 2,6-diisopropyl phenyl The 1-adamantyl Benzoyl
C-30 2,6-diisopropyl phenyl The 1-phenylethyl Benzoyl
C-31 2,6-diisopropyl phenyl Sec.-propyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-32 2,6-diisopropyl phenyl The tertiary butyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-33 2,6-diisopropyl phenyl Cyclohexyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-34 2,6-diisopropyl phenyl Cyclo-dodecyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-35 2,6-diisopropyl phenyl The 1-adamantyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-36 2,6-diisopropyl phenyl The 1-phenylethyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-37 (the chloro-6-methyl of 2-) phenyl Sec.-propyl T-butyldiphenylsilyl
C-38 (the chloro-6-methyl of 2-) phenyl The tertiary butyl T-butyldiphenylsilyl
C-39 (the chloro-6-methyl of 2-) phenyl Cyclohexyl T-butyldiphenylsilyl
C-40 (the chloro-6-methyl of 2-) phenyl Cyclo-dodecyl T-butyldiphenylsilyl
C-41 (the chloro-6-methyl of 2-) phenyl The 1-adamantyl T-butyldiphenylsilyl
C-42 (the chloro-6-methyl of 2-) phenyl The 1-phenylethyl T-butyldiphenylsilyl
C-43 (the chloro-6-methyl of 2-) phenyl Sec.-propyl Benzoyl
C-44 (the chloro-6-methyl of 2-) phenyl The tertiary butyl Benzoyl
C-45 (the chloro-6-methyl of 2-) phenyl Cyclohexyl Benzoyl
C-46 (the chloro-6-methyl of 2-) phenyl Cyclo-dodecyl Benzoyl
C-47 (the chloro-6-methyl of 2-) phenyl The 1-adamantyl Benzoyl
C-48 (the chloro-6-methyl of 2-) phenyl The 1-phenylethyl Benzoyl
C-49 (the chloro-6-methyl of 2-) phenyl Sec.-propyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-50 (the chloro-6-methyl of 2-) phenyl The tertiary butyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-51 (the chloro-6-methyl of 2-) phenyl Cyclohexyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-52 (the chloro-6-methyl of 2-) phenyl Cyclo-dodecyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-53 (the chloro-6-methyl of 2-) phenyl The 1-adamantyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-54 (the chloro-6-methyl of 2-) phenyl The 1-phenylethyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-55 The tertiary butyl Sec.-propyl T-butyldiphenylsilyl
Sequence number R 1 R 2 R 3a
C-56 The tertiary butyl The tertiary butyl T-butyldiphenylsilyl
C-57 The tertiary butyl Cyclohexyl T-butyldiphenylsilyl
C-58 The tertiary butyl Cyclo-dodecyl T-butyldiphenylsilyl
C-59 The tertiary butyl The 1-adamantyl T-butyldiphenylsilyl
C-60 The tertiary butyl The 1-phenylethyl T-butyldiphenylsilyl
C-61 The tertiary butyl Sec.-propyl Benzoyl
C-62 The tertiary butyl The tertiary butyl Benzoyl
C-63 The tertiary butyl Cyclohexyl Benzoyl
C-64 The tertiary butyl Cyclo-dodecyl Benzoyl
C-65 The tertiary butyl The 1-adamantyl Benzoyl
C-66 The tertiary butyl The 1-phenylethyl Benzoyl
C-67 The tertiary butyl Sec.-propyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-68 The tertiary butyl The tertiary butyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-69 The tertiary butyl Cyclohexyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-70 The tertiary butyl Cyclo-dodecyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-71 The tertiary butyl The 1-adamantyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
C-72 The tertiary butyl The 1-phenylethyl 4,5-dimethoxy-2-nitro carbobenzoxy-(Cbz)
In the preferred embodiment of this second aspect, the inventive method is for the preparation of the compound of general formula I-E:
Figure BDA00003115671900351
Wherein M, R 1, R 2, R 3and R 8there is above-mentioned implication.In this embodiment, R 1and R 2preferably there are different implications.
R 1be preferably selected from the group of formula IV.1-IV.5, particularly preferably the group of formula IV.1 and IV.2.More preferably R 1be selected from C 1-C 6alkyl, phenyl and with 1,2 or 3 independently selected from C 1-C 6the phenyl of the group of alkyl and chlorine.Especially preferred R 1be selected from the tertiary butyl, 2,6-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropyl phenyl and (the chloro-6-methyl of 2-) phenyl.
Preferred R 2be selected from alkyl and cycloalkyl, especially C 1-C 6alkyl, phenyl-C 1-C 6alkyl and C 5-C 15cycloalkyl.R 2especially be selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, isobutyl-, cyclopentyl, cyclohexyl, cyclo-dodecyl and 1-adamantyl.
Preferred R 3be selected from hydrogen, alkyl, cycloalkyl and aryl, more preferably hydrogen, C 1-C 6alkyl and C 6-C 10aryl.
Preferred R 8be selected from hydrogen, alkyl, cycloalkyl and aryl, more preferably hydrogen, C 1-C 6alkyl and C 6-C 10aryl.
M is preferably selected from PdCl 2(CNR 1), PtCl 2(CNR 1), PdCl (CNR 1) 2, Au (CNR 1) and AuCl, wherein R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl.
In the especially preferred embodiment of this second aspect, the inventive method is for the preparation of formula I-E.1 compound:
Figure BDA00003115671900361
Wherein M, R 1and R 2there is above-mentioned implication, especially as the implication of preferably mentioning.
The compound of general formula shown in following table 16-20 (I-E.1) itself has represented the preferred embodiments of the invention.R shown in following table D 1and R 2implication mean equally independently of each other and the embodiment of the present invention of combinatorial optimization especially.
Table 16
Wherein group M is PdCl 2(CNR 1) and R 1and R 2combination for compound in each case corresponding to formula (I-E.1) compound of a line of table D.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl 2(CNR 1) in residue R 1all there is identical meanings.
Table 17
Wherein group M is PtCl 2(CNR 1) and R 1and R 2combination for compound in each case corresponding to formula (I-E.1) compound of a line of table D.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PtCl 2(CNR 1) in residue R 1all there is identical meanings.
Table 18
Wherein group M is PdCl (CNR 1) 2and R 1and R 2combination for compound in each case corresponding to formula (I-E.1) compound of a line of table D.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl (CNR 1) 2in residue R 1all there is identical meanings.
Table 19
Wherein group M is AuCl and R 1and R 2combination for compound in each case corresponding to formula (I-E.1) compound of a line of table D.
Table 20
Wherein group M is Au (CNR 1) and R 1and R 2combination for compound in each case corresponding to formula (I-E.1) compound of a line of table D.Residue R with the theheterocyclic nitrogen atom bonding 1with at group Au (CNR 1) in residue R 1all there is identical meanings.
Table D
Sequence number R 1 R 2
D-1 2,6-3,5-dimethylphenyl Sec.-propyl
D-2 2,6-3,5-dimethylphenyl The tertiary butyl
D-3 2,6-3,5-dimethylphenyl Cyclohexyl
D-4 2,6-3,5-dimethylphenyl Cyclo-dodecyl
D-5 2,6-3,5-dimethylphenyl The 1-adamantyl
D-6 2,6-3,5-dimethylphenyl The 1-phenylethyl
D-7 2,4,6-trimethylphenyl Sec.-propyl
D-8 2,4,6-trimethylphenyl The tertiary butyl
D-9 2,4,6-trimethylphenyl Cyclohexyl
D-10 2,4,6-trimethylphenyl Cyclo-dodecyl
D-11 2,4,6-trimethylphenyl The 1-adamantyl
D-12 2,4,6-trimethylphenyl The 1-phenylethyl
D-13 2,6-diisopropyl phenyl Sec.-propyl
D-14 2,6-diisopropyl phenyl The tertiary butyl
D-15 2,6-diisopropyl phenyl Cyclohexyl
D-16 2,6-diisopropyl phenyl Cyclo-dodecyl
D-17 2,6-diisopropyl phenyl The 1-adamantyl
D-18 2,6-diisopropyl phenyl The 1-phenylethyl
D-19 (the chloro-6-methyl of 2-) phenyl Sec.-propyl
D-20 (the chloro-6-methyl of 2-) phenyl The tertiary butyl
D-21 (the chloro-6-methyl of 2-) phenyl Cyclohexyl
D-22 (the chloro-6-methyl of 2-) phenyl Cyclo-dodecyl
D-23 (the chloro-6-methyl of 2-) phenyl The 1-adamantyl
D-24 (the chloro-6-methyl of 2-) phenyl The 1-phenylethyl
D-25 The tertiary butyl Sec.-propyl
D-26 The tertiary butyl The tertiary butyl
D-27 The tertiary butyl Cyclohexyl
D-28 The tertiary butyl Cyclo-dodecyl
D-29 The tertiary butyl The 1-adamantyl
D-30 The tertiary butyl The 1-phenylethyl
In the preferred embodiment of this third aspect, the inventive method is for the preparation of the compound of general formula I-F:
Figure BDA00003115671900381
Wherein M, EWG, R 1, R 2, R 4, R 7and R 8there is above-mentioned implication.In this embodiment, R 1and R 2preferably there are different implications.
In this embodiment, R 1be preferably selected from phenyl, naphthyl, with 1,2 or 3 independently selected from C 1-C 8alkyl and C 1-C 8the phenyl of the group of haloalkyl and with 1,2 or 3 independently selected from C 1-C 8alkyl and C 1-C 8haloalkyl, especially C 1-C 6alkyl or C 1-C 6the naphthyl of the group of fluoroalkyl.R 1especially be selected from 2,6-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropyl phenyl, 2-trifluoromethyl, 2,6-bis-(trifluoromethyl) phenyl, 1-naphthyl and 2-naphthyl.
R 2be preferably selected from alkyl and cycloalkyl, especially C 1-C 6alkyl, phenyl-C 1-C 6alkyl and C 5-C 15cycloalkyl.More preferably R 2be selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, isobutyl-, 1-phenylethyl, cyclopentyl, cyclohexyl, cyclo-dodecyl and 1-adamantyl.
R 4be preferably selected from hydrogen, alkyl, cycloalkyl and aryl, more preferably hydrogen and C 1-C 10alkyl.
Preferred R 7and R 8be selected from independently of each other hydrogen, alkyl, cycloalkyl and aryl, more preferably hydrogen and C 1-C 10alkyl.
EWG is preferably C (O) R 14or C (O) OR 14, C (O) OR especially 14.R in this embodiment 14be preferably C 1-C 6alkyl, especially C 1-C 4alkyl, as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-or the tertiary butyl.
M is preferably selected from PdCl 2(CNR 1), PtCl 2(CNR 1), PdCl (CNR 1) 2, Au (CNR 1) and AuCl, wherein R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl.
The compound of preferred formula I-F.1:
Figure BDA00003115671900382
Wherein EWG, M, R 1and R 2there is above-mentioned implication, preferably as preferably mention those.
The compound of general formula shown in following table 21-30 (I-F.1) itself has represented the preferred embodiments of the invention.R shown in following table E 1and R 2implication mean equally independently of each other and the embodiment of the present invention of combinatorial optimization especially.
Table 21
Wherein group M is PdCl 2(CNR 1), EWG is methoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl 2(CNR 1) in residue R 1there is identical meanings.
Table 22
Wherein group M is PtCl 2(CNR 1), EWG is methoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PtCl 2(CNR 1) in residue R 1all there is identical meanings.
Table 23
Wherein group M is PdCl (CNR 1) 2, EWG is methoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl (CNR 1) 2in residue R 1all there is identical meanings.
Table 24
Wherein group M is AuCl, and EWG is methoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.
Table 25
Wherein group M is Au (CNR 1), EWG is methoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group Au (CNR 1) in residue R 1all there is identical meanings.
Table 26
Wherein group M is PdCl 2(CNR 1), EWG is ethoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl 2(CNR 1) in residue R 1there is identical meanings.
Table 27
Wherein group M is PtCl 2(CNR 1), EWG is ethoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PtCl 2(CNR 1) in residue R 1all there is identical meanings.
Table 28
Wherein group M is PdCl (CNR 1) 2, EWG is ethoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group PdCl (CNR 1) 2in residue R 1all there is identical meanings.
Table 29
Wherein group M is AuCl, and EWG is ethoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.
Table 30
Wherein group M is Au (CNR 1), EWG is ethoxycarbonyl and R 1and R 2combination for compound in each case corresponding to formula (I-F.1) compound of a line of table E.Residue R with the theheterocyclic nitrogen atom bonding 1with at group Au (CNR 1) in residue R 1all there is identical meanings.
Table E
Sequence number R 1 R 2
E-1 2,6-3,5-dimethylphenyl Sec.-propyl
E-2 2,6-3,5-dimethylphenyl The tertiary butyl
E-3 2,6-3,5-dimethylphenyl Cyclohexyl
E-4 2,6-3,5-dimethylphenyl Cyclo-dodecyl
E-5 2,6-3,5-dimethylphenyl The 1-adamantyl
E-6 2,6-3,5-dimethylphenyl The 1-phenylethyl
E-7 2,4,6-trimethylphenyl Sec.-propyl
E-8 2,4,6-trimethylphenyl The tertiary butyl
E-9 2,4,6-trimethylphenyl Cyclohexyl
E-10 2,4,6-trimethylphenyl Cyclo-dodecyl
E-11 2,4,6-trimethylphenyl The 1-adamantyl
E-12 2,4,6-trimethylphenyl The 1-phenylethyl
E-13 2,6-diisopropyl phenyl Sec.-propyl
E-14 2,6-diisopropyl phenyl The tertiary butyl
E-15 2,6-diisopropyl phenyl Cyclohexyl
E-16 2,6-diisopropyl phenyl Cyclo-dodecyl
E-17 2,6-diisopropyl phenyl The 1-adamantyl
E-18 2,6-diisopropyl phenyl The 1-phenylethyl
Sequence number R 1 R 2
E-19 (2-trifluoromethyl) phenyl Sec.-propyl
E-20 (2-trifluoromethyl) phenyl The tertiary butyl
E-21 (2-trifluoromethyl) phenyl Cyclohexyl
E-22 (2-trifluoromethyl) phenyl Cyclo-dodecyl
E-23 (2-trifluoromethyl) phenyl The 1-adamantyl
E-24 (2-trifluoromethyl) phenyl The 1-phenylethyl
E-25 The 1-naphthyl Sec.-propyl
E-26 The 1-naphthyl The tertiary butyl
E-27 The 1-naphthyl Cyclohexyl
E-28 The 1-naphthyl Cyclo-dodecyl
E-29 The 1-naphthyl The 1-adamantyl
E-30 The 1-naphthyl The 1-phenylethyl
E-31 The 2-naphthyl Sec.-propyl
E-32 The 2-naphthyl The tertiary butyl
E-33 The 2-naphthyl Cyclohexyl
E-34 The 2-naphthyl Cyclo-dodecyl
E-35 The 2-naphthyl The 1-adamantyl
E-36 The 2-naphthyl The 1-phenylethyl
step a1)
Step a1 in the inventive method), in, use general formula (II) R 1the isocyanide complex of-N ≡ C-M, wherein R 1with M above having to one of implication.
synthetic isonitrile part
Be applicable to providing the synthetic of isonitrile of the isocyanide complex of general formula (II) ordinary method by brief description to be realized by the commercially available or precursor that can be obtained by currently known methods.The method that is applicable to the formation isonitrile is for example that the methane amide replaced by N-is eliminated water, the reduction of the reaction between primary amine and chloroform under alkaline condition (haloform-isocyanide conversion) and isocyanic ester.General formula R is provided 1the preferred method of the isonitrile of-N ≡ C is to make amine R as shown in scheme 1 1-NH 2react at elevated temperatures and obtain formula R with manthanoate 1the methane amide of-NH-CH (=O) is also eliminated water subsequently, for example uses POCl 3eliminate water with tertiary amine, phosgene and tertiary amine etc.
Scheme 1:
Figure BDA00003115671900411
In scheme 1, R 1have above-mentioned implication, especially, as the implication of preferably mentioning, Et refers to ethyl.
the isocyanide complex of synthetic general formula (II)
In the methods of the invention, required metal carbene title complex is by isonitrile part (isocyanide part) preparation of metal-complexing.General formula used (II) R 1the isocyanide complex of-N ≡ C-M for example can be by above-mentioned carbomethoxyisopropyl isonitrate R as shown in scheme 2 1the title complex that the is easy to get ligand exchange reaction known by those skilled in the art of-N ≡ C and metal M obtains.Preferred educt title complex (educt complex) is for example [Pd (CH 3cN) 2cl 2], [Pt (CH 3cN) 2cl 2] and [AuCl (tetramethylene sulfide)].
Scheme 2 (synthetic Pd (II)-and Au (I)-and Pt (II)-isocyanide complex):
In scheme 2, R 1there is above-mentioned implication, especially as the implication of preferably mentioning.
synthetic NHC title complex
In order to obtain required NHC title complex, the isocyanide complex of general formula (II) is reacted with general formula (III) or compound (IIIa):
Figure BDA00003115671900422
Wherein
N, R 2, R 3, R 4, R 5, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y is leavings group, if or R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, Y is group O-Y a, Y wherein afor the alkyl that does not replace or replace, the aryl that does not replace or replace, the alkyl-carbonyl that does not replace or replace or the aryl carbonyl that does not replace or replace.
Negatively charged ion Equivalent X -only as counter ion and can freely be selected from univalent anion and corresponding to the multivalent anions part of single negative charge.Suitable negatively charged ion is for example halide ions X -, for example chlorion and bromide anion, sulfate radical and azochlorosulfonate acid anion, for example SO 4 2-, tosylate, trifluoromethayl sulfonic acid root and methanesulfonic root.X -be preferably chlorion or bromide anion.
Preferably Y is selected from halogenide, tosylate, carboxylicesters, carbonic ether, ester, sulphonate and phosphoric acid ester.The example of Y is chlorine, bromine, iodine, methane sulfonate, trifluoromethayl sulfonic acid ester and tosylate, preferably chlorine and bromine.
Preferred Y abe selected from C 1-C 4alkyl and pentafluorophenyl group carbonyl.
In the first preferred embodiment, formula (III) compound is the omega-halogenated alkyl groups ammonium salt, preferably 2-(halogenated ethyl) ammonium halide or 3-(halopropyl) ammonium halide.Equally, in another first preferred embodiment, formula (III.a) compound is omega-halogenated alkyl groups amine, preferably 2-(halogenated ethyl) amine or 3-(halopropyl) amine.
2-(chloroethyl) amine that formula (III) compound is especially formula (III.1.a) for 2-(chloroethyl) ammonium chloride of formula (III.1) and formula (III.a) compound:
Figure BDA00003115671900431
Wherein
R 2be selected from alkyl and cycloalkyl, especially C 1-C 6alkyl, phenyl-C 1-C 6alkyl and C 5-C 15cycloalkyl,
R 3, R 4, R 7and R 8be selected from hydrogen, C 1-C 6alkyl and C 6-C 10aryl.
Preferably at compound (III.1) with (III.1.a), R 2be selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, cyclo-dodecyl and 1-adamantyl.
Preferably at compound (III.1) with (III.1.a), R 3, R 4, R 7and R 8be selected from hydrogen and phenyl.In particular embodiments, R 3, R 4, R 7and R 8be all hydrogen.In another particular embodiments, residue R 3, R 4, R 7and R 8in one be phenyl and other be hydrogen.
Omega-halogenated alkyl groups ammonium salt (III) and free alkali thereof, the synthetic of omega-halogenated alkyl groups amine compound (III.a) can be as realized by ordinary method in scheme 3 as shown in ω-chlorine alkylammonium salt.Therefore, 2-(chloroethyl) ammonium chloride synthetic can according to the document program by commercially available amino alcohol start to carry out (such as referring to A.Habtemariam etc., J.Chem.Soc.Dalton Trans.2001,8,1306-1318).The unhindered amina of formula (III.1.a) is by adding alkali to be discharged by the salt of formula (III.1).Suitable alkali is for example that tertiary amine is as triethylamine.
Scheme 3 (synthetic 2-(chloroethyl) ammonium chloride and 2-(chloroethyl) amine compound)
Figure BDA00003115671900441
In scheme 3, R 2, R 3, R 4, R 7and R 8there is above-mentioned implication, especially as the implication of preferably mentioning.
The synthetic of 2-(diamantane-1-base amino) ethanol as the raw material that forms corresponding 2-(chloroethyl) ammonium chloride can be as P.E.Aldrich, E.C.Herrmann, W.E.Meier, M.Paulshock, W.W.Prichard, J.A.Snyder and J.C.Watts, at J.Med.Chem.1971, carry out described in 14,535-543.
In the second preferred embodiment, formula (III) compound is ω-(carbalkoxy) alkylammonium salt, preferably 2-(C 1-C 4carbalkoxy) ethyl ammonium halide or 3-(C 1-C 4carbalkoxy) propyl group ammonium halide.Equally, in the second preferred embodiment, formula (III.a) compound is ω-(carbalkoxy) alkylamine, preferably 2-(C 1-C 4carbalkoxy) ethylamine or 3-(C 1-C 4carbalkoxy) propyl group amine.
Formula (III) compound is especially the 2-(C of formula (III.2) 1-C 4carbalkoxy) 2-(C that ethyl ammonium chloride and formula (III.a) compound is formula (III.2.a) 1-C 4carbalkoxy) ethylamine:
Figure BDA00003115671900442
Wherein
R 2be selected from alkyl and cycloalkyl, especially C 1-C 6alkyl, phenyl-C 1-C 6alkyl and C 5-C 15cycloalkyl; R 3, R 4, R 7and R 8be selected from hydrogen, C 1-C 6alkyl and C 6-C 10aryl.
Preferred R at compound (III.2) and (III.2.a) 2be selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, cyclo-dodecyl and 1-adamantyl.
Preferably at compound (III.2) with (III.2.a), R 3, R 4, R 7and R 8be selected from hydrogen and phenyl.In particular embodiments, R 3, R 4, R 7and R 8be all hydrogen.In another particular embodiments, R 3, R 4, R 7and R 8in one be phenyl and other be hydrogen.
In order to obtain required NHC-title complex, the isocyanide complex of general formula (II) is reacted with general formula (III) or compound (III.a).
Preferably this reaction is at alkali, and more preferably tertiary amine, especially triethylamine carry out under existing.
Suitable temperature of reaction is generally-10 ° of C to 100 ° of C, preferably-0 ° of C to 50 ° of C.In preferred embodiments, this reaction is carried out at ambient temperature.
The step a1 of the inventive method) can under the respective reaction condition, be in the suitable solvent of inertia and carry out.Normally suitable solvent be for example aromatic hydrocarbons as toluene and xylene, hydro carbons or hydrocarbon mixture are as hexanaphthene, ethers is as t-butyl methyl ether, Isosorbide-5-Nitrae-bis-
Figure BDA00003115671900451
alkane and tetrahydrofuran (THF), alcohols is as methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol, and ketone is as acetone and methyl ethyl ketone etc.
Advantageously reaction and display of the present invention goes out to the conversion fully of NHC title complex (I).This reaction for example can be passed through the skew monitoring of the IR-stretching frequency of this isonitrile part.The method is also successfully in for example by use piperidines or derivatives thereof, as precursor, forming dicyclo NHC title complex.
step b1)
R wherein 3and R 4with the carbon atom of their institute's bondings together for C=O and wherein the ring carbon atom adjacent with carbonyl can form corresponding enol tautomer with the compound of the general formula (I) of hydrogen atom, this in scheme 4 as to compound (I-B.1) with (I-B.2).These tautomers are also introduced in the present invention.
Scheme 4 (keto-enol tautomerism body)
Figure BDA00003115671900461
In scheme 4, M, R 1, R 2, R 6, R 7and R 8there is above-mentioned implication, especially as the implication of preferably mentioning.
Can make the formula (I) that obtains in a) in step but the enolization compound at step b1) in suitable electrophilic reagent, further react.
Therefore, can make wherein R 3and R 4with together with the carbon atom of their institute's bondings for the compound of the general formula of C=O (I) for example with compound R that wherein Z is leavings group 3a-Z is further reaction under appropriate base exists.Preferably Z is selected from halogenide, tosylate, carboxylicesters, carbonic ether, ester, sulphonate and phosphoric acid ester.The example of Z is chlorine, bromine, iodine, methane sulfonate, trifluoromethayl sulfonic acid ester and tosylate, preferably chlorine and bromine.
Step b1) in, alkali used is preferably non-nucleophilicity alkali, alkali metal ammonia compound alkali, for example lithium diisopropylamine, two (trimethyl silyl) Lithamide, two (trimethyl silyl) sodium amide, two (trimethyl silyl) potassium amide more preferably are obstructed.
Step b1) reaction in usually at-78 ° of C to envrionment temperature, preferably at the temperature of-78 ° of C to 0 ° of C, carry out.
step a2)
Step a2 in the inventive method), in, the isocyanide complex of general formula (II) is reacted with the amine of formula (V):
Figure BDA00003115671900462
Wherein
R 2, R 3and R 8above having to one of implication, one of preferred meaning especially; And
R 10and R 11above having to one of implication; Preferred R 10and R 11for methyl or ethyl or R 10and R 11form together ethylene or trimethylene structure division, carbon atom wherein can not be substituted or can be all or part of by methyl substituted;
Obtain the midbody compound of formula VI:
R wherein 1, R 2, R 3, R 8, R 10, R 11with M above having to one of implication, one of preferred meaning especially.
This reaction is carried out usually in inert organic solvents.Suitable solvent is halogenated hydrocarbon, as methylene dichloride or trichloromethane, and ethers, as Di Iso Propyl Ether, t-butyl methyl ether, two
Figure BDA00003115671900472
alkane, phenylmethylether, tetrahydrofuran (THF) and glycol dimethyl ether.This reaction, usually at 0-80 ° of C, is preferably carried out at the temperature of 10-40 ° of C.
Step a2) reaction in for example can be passed through the skew monitoring of the IR-stretching frequency of this isonitrile part.All productive rates are all excellent.
According to another particular embodiments, step a2) shown in method be used to form wherein R 1and R 2formula VI compound with different implications.
Preferably in formula VI compound, R 1be preferably selected from the group of formula IV.1-IV.5, particularly preferably the group of formula IV.1 and IV.2.More preferably R 1be selected from C 1-C 6alkyl, phenyl and with 1,2 or 3 independently selected from C 1-C 6the phenyl of the group of alkyl and chlorine.Especially preferred R 1be selected from the tertiary butyl, 2,6-3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,6-diisopropyl phenyl and (the chloro-6-methyl of 2-) phenyl.
Preferably in formula VI compound, R 2be selected from alkyl and cycloalkyl, especially C 1-C 6alkyl, phenyl-C 1-C 6alkyl and C 5-C 15cycloalkyl.R 2especially be selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, isobutyl-, cyclopentyl, cyclohexyl, cyclo-dodecyl and 1-adamantyl.
Preferably in formula VI compound, R 3and R 8be selected from independently of each other hydrogen, C 1-C 6alkyl and C 6-C 10aryl.
Preferably in formula VI compound, R 10and R 11be selected from independently of each other C 1-C 4alkyl.
Preferably, in formula VI compound, M is PdCl 2(CNR 1), PtCl 2(CNR 1), PdCl (CNR 1) 2, Au (CNR 1) and AuCl, wherein R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl.M is especially AuCl.
Formula VI compound is new and therefore also forms a part of the present invention.They are air and hydrostabile and can at room temperature store and not decompose normally.
Step b2)
At step b2) in as shown in scheme 5 with the midbody compound of acid treatment formula (VI), obtain on the spot having carbonyl functional group's corresponding compound (VII), in molecule, closed loop obtains formula I-E compound subsequently.
Scheme 5:
Figure BDA00003115671900481
In scheme 5, R 1, R 2, R 3, R 8, R 10, R 11with M above having to one of implication, one of preferred meaning especially.
Step I in scheme 5) in, use the acid treatment compound VI, obtain midbody compound VII, it is at step I i) in further be reacted into Compound I-E.Suitable acid is mineral acid (inorganic acid) or organic acid.The example of suitable inorganic acid is mineral acid (mineral acid) as HCl or organic acid as tosic acid.The step I of scheme 5) usually under hydrolysising condition, carry out.Suitable solvent is at step a1) in mention those.
Temperature of reaction is generally-10 ° of C to 100 ° of C, preferably 0-50 ° of C.
Formula V compound can obtain as shown in scheme 6.
Scheme 6:
Figure BDA00003115671900491
In scheme 6, R 1, R 2, R 3, R 8, R 10and R 11above having, institute is to one of implication, especially conduct preferably those one of.
Step I in scheme 6) in, with formula (VIII) compound treatment amine R 1-NH 2, obtain the imines of formula (IX).This reaction is advantageously carried out under dewatering agent exists as sal epsom.This reaction is carried out usually under solvent exists.Suitable solvent is that halogenated aliphatic, alicyclic or aromatic hydrocarbons are as methylene dichloride.Step I i in scheme 6), in, the reduction of the group with imine moiety of formula IX is obtained to amine compound V.Suitable reductive agent is that hydride is as lithium aluminum hydride or sodium borohydride.This reaction is carried out usually under solvent exists.Suitable solvent is C 1-C 4alkanol is as methyl alcohol or ethanol.
Step a3)
In the methods of the invention, according to scheme a3) the required NHC title complex with formula I-F:
Figure BDA00003115671900492
R wherein 1, R 2, R 4, R 7, R 8, M and EWG above having to one of implication, preferably there is one of preferred meaning,
Can react and prepare with the amine of formula III b or IIIc by the isocyanide complex that makes formula IIa:
Wherein
R 2, R 4, R 7and R 8above having to one of implication;
X -for the negatively charged ion Equivalent; And
EWG is C (O) R 14, C (O) OR 14, NO 2, S (O) R 14or S (O) 2r 14, R wherein 14for hydrogen, alkyl, cycloalkyl or aryl.
This reaction is carried out usually in organic solvent.Suitable organic solvent be aprotic solvent as halogenated paraffin, methylene dichloride for example.
According to the present invention and/or the compound of general formula obtained by the method for the present invention (I) can be advantageously used in the reaction of NHC metal complexes catalysis.The compound of general formula (I) is preferably used as that C-C, C-O, C-N or c h bond form in reaction used catalyst or for this catalyzer.They are particularly useful for being selected from the C-C linked reaction of Suzuki reaction, Heck reaction, Sonogashira reaction, Stille reaction, Hartwig-Buchwald reaction and Kumada reaction.In addition, they are particularly useful for being selected from the reaction of hydrogenation, hydroformylation, hydrosilylation, Hartwig-Buchwald reaction and acid amides alpha-aromatic.(for the C-C key by cross-coupling, form, referring to S.P.Nolan and O.Navarro, Comprehensive Organometallic Chemistry III, the 11st volume, the 1st edition (editor: A.Canty), Elsevier, Oxford, 2007, the 11.01 chapters, 1-38 and the reference of wherein quoting; B) F.Glorius, Top.Organomet.Chem.2007,21,1-20; C) E.A.B.Kantchev, C.J.O ' Brien and M.J.Organ, Aldrichimica Acta2006,39,97-111)
suzuki cross-coupling (Suzuki-Miyaura cross-coupling)
Palladium catalysis cross-coupling reaction between organoboron compound and Organohalogen compounds or triflate provides the strong universal method that forms C-C.Due to their element task in palladium catalysis cross-coupling field, the Nobel chemistry Prize of 2010 is authorized A.Suzuki jointly, R.F.Heck and E.i Negishi.The relevant information of using the NHC metal complexes in Suzuki reaction can be in a) W.A.Herrmann, C.P.Reisinger, M.Spiegler, J.Organomet.Chem.1998,557,93; B) C.M.Zhang, J.K.Huang, M.L.Trudell, S.P.Nolan, J.Org.Chem.1999,64,3804; C) A.F ü rstner, A.Leitner, Synlett.2001,290; D) C.W.K.Gstottmayr, V.P.W.
Figure BDA00003115671900501
e.Herdtweck, M.Grosche, W.A.Herrmann, Angew.Chem.Int.Ed.2002, find in 41,1363.
Preferably the compound of general formula (I) is used for to following reaction:
Figure BDA00003115671900511
Wherein
R abe selected from each case the alkyl, alkenyl, alkynyl and the aryl that do not replace or replace,
R bbe selected from alkyl, alkoxyl group and hydroxyl,
R cbe selected from each case the alkyl, alkenyl and the aryl that do not replace or replace,
E is selected from Cl, Br, I, CF 3sO 3, (OR d) 2p (=O) O, wherein R dfor hydrogen, alkyl, cycloalkyl or aryl,
This alkali is preferably selected from alkali metal hydroxide, alkaline earth metal hydroxides, alkaline carbonate, alkaline earth metal carbonate, thallic hydroxide (I), alkanol thallium (I), alkali metal phosphate, alkaline metal fluoride cpd.The example of appropriate base is NaOH, KOH, Na 2cO 3, K 2cO 3, Cs 2cO 3, Ba (OH) 2, K 3pO 4, TlOH, ethanol thallium (I), KF, CsF, (C 4h 9) 4nF, sodium ethylate, potassium ethylate and potassium tert.-butoxide.
The compound of general formula (I) is particularly useful in following reaction:
Cat.: the catalyzer of formula (I)
the Sonogashira reaction
The palladium that the Sonogashira cross-coupling reaction is Terminal Acetylenes hydrocarbon and aryl halide or vinyl halide (and usually also having copper) catalytic coupling obtains eneyne.The relevant information of using the NHC metal complexes in Sonogashira reaction can be at a) S.Caddick, F.G.N.Cloke, G.K.B.Clentsmith, P.B.Hitchcock, D.McKerrecher, L.R.Titcomb, M.R.V.Williams, J.Organomet.Chem.2001,617; B) C.L.Yang, S.P.Nolan, Organometallics2002,21,1020; C) L.Ray, S.Barman, M.M.Shaikh, P.Ghosh, Chem.Eur.J.2008, find in 14,6646.
The compound of general formula (I) is preferred in following reaction:
Figure BDA00003115671900521
Wherein
R ebe selected from each case the alkenyl, aryl and the heteroaryl that do not replace or replace,
R fbe selected from hydrogen, alkyl, alkenyl, aryl and Si (R g) 3,
R gbe selected from each case the alkyl, cycloalkyl and the aryl that do not replace or replace,
E is selected from Cl, Br, I, CF 3sO 3,
This alkali is generally amine, alkane alkoxide, alkaline earth metal carbonate or alkaline carbonate.Preferably this alkali is selected from secondary alkylamine, alkyl amine, basic metal alkanoate and alkaline carbonate.This amine compound can excessive use and also as solvent.
Preferred solvent for the Sonogashira reaction is CH 3cN, DMF (dimethyl formamide), THF (tetrahydrofuran (THF)) or ethyl acetate.
Preferred bases for the Sonogashira reaction is N (C 2h 5) 3, HN (C 2h 5) 2, N (iso-C 3h 7) 2(C 2h 5), KO (uncle-C 4h 9), K 2cO 3and Cs 2cO 3.
The compound of general formula (I) is particularly useful in the reaction of bromobenzene and 1-hexin.Do not use extra copper source.
The relevant information of using the NHC metal complexes in Heck reaction can be at a) W.A.Herrmann, M.Elison, J.Fischer, C.
Figure BDA00003115671900522
g.R.J.Artus, Angew.Chem.Int.Ed.1995,34,2371; B) E.A.B.Kantchev, C.J.O ' Brien, M.G.Organ, Angew.Chem.Int.Ed.2007,46,2768; C) J.Ye, W.Chen, D.Wang, Dalton Trans.2008, find in 30,4015.
The relevant information of NHC metal complexes of using in Stille reaction can be at G.A.Grasa, S.P.Nolan, and Org.Lett.2001, find in 3,119.
The relevant information of NHC metal complexes of using in the Kumada reaction can be at V.P.W.
Figure BDA00003115671900523
t.Weskamp, C.W.K. w.A.Herrmann, Angew.Chem.Int.Ed.2000, find in 39,1602.
The relevant information of using the NHC metal complexes in Hartwig-Buchwald reaction can be at a) S.R.Stauffer, S.W.Lee, J.P.Stambuli, S.I.Hauck, J.F.Hartwig, Org.Lett.2000,2,1423, b) J.Huang, G.Grasa, S.P.Nolan, in Org.Lett.1999,1,1307, find.
The relevant information of NHC metal complexes of using in the alpha-aromatic of acid amides can be at S.Lee, J.F.Hartwig, and J.Org.Chem.2001, find in 66,3402.
The relevant information of using the NHC metal complexes in hydrogenation can be in a) H.M.Lee, T.Jiang, E.D.Stevens, S.P.Nolan, Organometallics2001,20,1255; B) L.D.Vazquez-Serrano, B.T.Owens, J.M.Buriak, Chem.Comm.2002,2518; C) D.Gnanamgari, E.L.O.Sauer, N.D.Schley, C.Butler, C.D.Incarvito, R.H.Crabtree, Organometallics2009,28,321; D) H.Turkmen, T.Pape, F.Hahn, C.Ekkehardt; Eur.J.Inorg.Chem.2008, find in 34,5418.
The relevant information of using the NHC metal complexes in hydroformylation can be at a) J.D.Scholten, J.Dupont, and Organometallics2008, find in 27,4439.
The relevant information of using the NHC metal complexes in hydrosilylation can be at b) W.A.Herrmann, L.J.Goossen, M.Spiegler, J.Organomet.Chem.1997, find in 547,357.
The following example illustrates the present invention and does not limit the present invention.
Embodiment
Universal method
All reagent and solvent be by Acros, ABCR, and Alfa Aesar, Sigma-Aldrich or VWR obtain and use under further not purifying, unless otherwise.Deuterated solvent is purchased from Euriso-Top.Anhydrous solvent passes through MB SPS-800 drying by drying tower.Preparation to the material of air and moisture-sensitive is used the Schlenk technology to carry out in the dry flask of flame under nitrogen atmosphere.Cross-coupling reaction carries out in the technical grade solvent.Use is from Macherey-Nagel's precoating plastics sheet SIL G/UV 254(SiO 2, 0.20mm is thick) and carry out tlc (TLC).Use is carried out column chromatography from the silica gel (40.0-63.0nm granularity) of Macherey-Nagel.NMR spectrum is at Bruker Avance500, record on Bruker Avance300 and Bruker ARX-250 spectrometer.Chemical shift (ppm) is located with respect to the residual solvent proton.Signal ambiguity is determined with s (unimodal), d (bimodal), t (triplet), q (quartet) or m (multiplet). 13the C ownership is via DEPT90 and DEPT135 or the realization of HSQC-me spectrum.MS spectrum is at Vakuum Generators ZAB-2F, record on FinniganMAT TSQ700 or JEOL JMS-700 spectrometer.GC spectrum is record on the HP Agilent5890Series II Plus with the FID analyser.GC-MS spectrum is record on the Agilent5890Series II Plus with the HP5972 spectrometry mass.IR spectrum (cm -1) record on Bruker Vector22FT-IR.Crystal structure analysis is carried out on Bruker Smart CCD or Bruker APEX diffractometer.Ultimate analysis is carried out on Elementar Vario EL.
Figure BDA00003115671900541
research exists
Figure BDA00003115671900542
on Mettler Toledo IC10, carry out.
Synthetic
I. raw material preparation
I.0 benzamide type is general synthetic
Figure BDA00003115671900543
R 1as defined above.
Amine (1) is dissolved in ethyl formate (15mL), heats 12 hours under 200 ° of C in autoclave and heat other 5 hours under 250 ° of C.Precipitation is leached and wash with Skellysolve A.Obtain benzamide compound (2) by acetone/sherwood oil (1/5) recrystallization with clear crystal.
I.1 synthesize the isonitrile part
I.1. the universal program for preparing carbomethoxyisopropyl isonitrate
R 1as defined above.
Methane amide (2) is dissolved in anhydrous methylene chloride.This solution was cooled to-60 ° of C and dripped POCl in 5 minute 3.By this suspension agitation 20 minutes and dripped triethylamine in 10 minutes.The gained yellow suspension is stirred and spends the night.Allow during this period cooling bath to be warmed to room temperature.Then room temperature is inclined on ice and be warmed to this suspension.Add methylene dichloride and separate each layer.The saturated NaHCO of organic layer 3solution washing 3 times.By organic phase Na 2sO 4dry also removal of solvent under reduced pressure.Crude product is by distillation or column chromatography (SiO 2) purify.
Example I: 2,4,6-trimethylphenyl isonitrile
2，4，6-trimethyl aniline (10g, 73.9mmol) is dissolved in ethyl formate (15ml).This mixture is heated 12 hours in autoclave under 200 ° of C.Then solid precipitation leached and wash with pentane.Using almost quantitative yield by acetone/sherwood oil (1/3) recrystallization and obtain N-(2,4,6-trimethylphenyl) methane amide (11.43g, 96%) as clear crystal.The data of all analytical data and former report (G.Vougioukalakis, J.Am.Chem.Soc.2008,130,2234-2245) in full accord.
By this methane amide (1g, 6.13mmol) be dissolved in anhydrous methylene chloride (DCM) (30ml) in.This solution was cooled to-60 ° of C and dripped POCl in 5 minute in ethanol/liquid nitrogen bath 3(1.67ml, 18.3mmol).By this suspension agitation 20 minutes and dripped triethylamine (5.57g, 55.0mmol) in 10 minutes.The gained yellow suspension is stirred and spends the night.Allow during this period cooling bath to be warmed to room temperature.Then room temperature is inclined on ice and be warmed to this suspension.Add DCM (30ml) and separate each layer.By the saturated NaHCO of organic layer 3solution washing (3 * 10ml).Organic phase NaSO 4dry also removal of solvent under reduced pressure.Crude product is by distillation (50-55 ° of C, 6.5 * 10 -2millibar) purify, with clear crystal, obtain title compound (637mg, 72%). 1h NMR (300MHz, CD 2cl 2): δ=2.23 (s, 3H ,-CH 3), 2.31 (s, 6H ,-CH 3), 6.95 (s, 2H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=17.19,19.53,127.01,133.16,137.55 (not observing other signals).The data of all analytical data and former report (G.Vougioukalakis, J.Am.Chem.Soc.2008,130,2234-2245) in full accord.
Example II: 2,6-diisopropyl phenyl isonitrile
2,6-DIPA (purity: 92%, 10g, 51.9mmol) is dissolved in ethyl formate (15ml).At first this mixture is heated 12 hours in autoclave under 200 ° of C, then heat 5 hours under 250 ° of C.Solid precipitation is leached and wash with pentane.Using almost quantitative yield by acetone/sherwood oil (1/5) recrystallization and obtain N-(2,6-diisopropyl phenyl) methane amide (9.48g, 46.2mmol, 89%) as clear crystal.This methane amide (1g, 4.87mmol) is dissolved in anhydrous DCM (10ml).This solution was cooled to-60 ° of C and dripped POCl in 5 minute in ethanol/liquid nitrogen bath 3(1.33ml, 14.6mmol).By this suspension agitation 20 minutes and dripped triethylamine (4.43g, 43.8mmol) in 10 minutes.The gained yellow suspension is stirred and spends the night.Allow during this period cooling bath to be warmed to room temperature.Then room temperature is inclined on ice and be warmed to this suspension.Add DCM (30ml) and separate each layer.The saturated NaHCO of organic layer 3solution washing (3 * 10ml).Organic phase Na 2sO 4dry also removal of solvent under reduced pressure.Crude product is by distillation (72-80 ° of C, 4.5 * 10 -2millibar) purify, with water white oil, obtain title compound (720mg, 3.84mmol, 79%).
1h NMR (300MHz, CD 2cl 2): δ=1.22 (d, 12H, J=7.0Hz ,-CH 3), 3.32 (m, 2H, J=6.9Hz ,-CH-), 7.14 (d, 2H, J=7.8Hz, ArH), 7.29 (t, 1H, J=7.7Hz, ArH); 13c NMR (75MHz, CD 2cl 2): δ=23.12,30.62,123.94,130.05,145.72 (not observing other signals).The data of all analytical data and former report (U.J.Kilgore, F.Basuli, J.C.Huffman, D.J.Mindiola, Inorg.Chem.2006,45,487-489) in full accord.
I.2 synthesize isonitrile-Pd title complex
Universal program:
By [Pd (CH 3cN) 2cl 2] be dissolved in toluene and add this isonitrile of 2 equivalents.This mixture is at room temperature stirred 12 hours.Precipitation is leached, with cold pentane washing drying under reduced pressure, obtain title compound.
EXAMPLE III: cis-[PdCl 2(2,6-3,5-dimethylphenyl isonitrile) 2]
By [Pd (CH 3cN) 2cl 2] (200mg, 780 μ mol) be dissolved in toluene (8ml) and add from 2 of example II 6-3,5-dimethylphenyl isonitrile (212mg, 1.60mmol).This mixture is stirred 12 hours at ambient temperature.Precipitation is leached, with cold pentane washing (3 * 10ml) drying under reduced pressure, with white solid, obtain title compound (333mg, 757 μ mol, 97%).
IR (KBr): ν=2363,2208,1632,1473,1384,1170,771,717,576,499,453; HRMS (FAB +) C 18h 18n 2clPd[M-Cl -] +: calculated value: 403.0193, measured value: 403.0138.
Below the compound of listed EXAMPLE IV, V, VI and VII in the mode that is similar to EXAMPLE III, prepare.
EXAMPLE IV: cis-[Pd (2,4,6-trimethylphenyl isonitrile) 2cl 2]
Obtain title compound (productive rate: 89%) with white solid.
IR (KBr): ν=2919,2210,1604,1471,1382,1308,1035,853,712,600,568,502,473; HR-MS (FAB +): calculated value: C 20h 22pdClN 3[M-Cl -] +=431.0506, measured value: 431.0486
EXAMPLE V: cis-[PdCl 2(2,6-diisopropyl phenyl isonitrile) 2]
Obtain title compound (productive rate: 83%) with yellow solid.
1h NMR (300MHz, CD 2cl 2): δ=1.21 (d, 12H, J=6.9Hz ,-CH 3), 3.26 (m, 2H ,-CH-), 7.17 (d, 2H, J=7.8Hz, ArH), 7.40 (t, 1H, J=7.9Hz, ArH); 13c NMR (75MHz, CD 2cl 2): δ=23.24 (q, 8C), 30.78 (d, 4C), 124.77 (d, 6C), 132.52 (s, 4C), 147.24 (s, 2C); IR (KBr): ν=2966.2927.2873,2209,1635,1585,1475,1458,1433,1388,1366,1356,1259,1183,1062,800,751,510,477cm -1; HR-MS (FAB +): m/z=515.1140, C 26h 34clN 2calculated value [the M-Cl of Pd -] +: 515.1145, m/z=480.1760, C 26h 34n 2calculated value [the M-2Cl of Pd -] +: 480.1757.
Example VI: cis-[PdCl 2(the chloro-6-aminomethyl phenyl of 2-isonitrile) 2]
Obtain title compound (productive rate: 95%) with white solid.
1h NMR (300MHz, CDCl 3): δ=2.45 (s; 3H ,-CH 3), 7.09-7.26 (m; 3H, ArH); IR (KBr): ν=2206,1632,1461,1177,873,782,711,569 13cNMR (75MHz, CDCl 3): δ=19.34,77.43,127.96,129.19,129.59,131.78,132.09,139.68; HRMS (FAB +) C 16h 12n 2cl 3pd[M-Cl -] +: calculated value: 442.9101, measured value: 442.9069
Example VII A: cis-[PdCl 2(tertiary butyl) 2]
Obtain title compound (productive rate: 92%) with white solid.The data of analytical data and former report (S.Otsuka, Y.Tatsuno, K.Ataka, J.Am.Chem.Soc1971,93,6705-6706) in full accord.
I.3 synthesize isonitrile-Au (I) title complex
Universal program:
Be dissolved in methylene dichloride (DCM) by 1 equivalent [AuCl (tetramethylene sulfide)] and at room temperature add 1 equivalent isonitrile.This mixture is stirred 15 minutes.Under reduced pressure except desolventizing.The crystallization crude product is used under further not purifying.
Example VII A I:[AuCl (2,4,6-trimethylphenyl isonitrile)]
[AuCl (tetramethylene sulfide)] (500mg, 1.56mmol) is dissolved in DCM (10ml) and adds from 2,4 of example I, 6-trimethylphenyl isonitrile (233mg, 1.56mmol).This mixture is stirred 12 hours at ambient temperature.Then except desolventizing and by pentane washing (3 * 10ml) for the gained white precipitate, with white solid, obtain this title complex (583mg, 1.54mmol, 99%).
1h NMR (300MHz, CD 2cl 2): δ=2.28 (s, 6H, CH 3), 2.34 (s, 3H, CH 3), 6.95 (s, 2H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=18.76,21.59,129.50,136.42,142.30; IR (KBr): ν=2917,2207 (NC), 1602,1474,1387,1308,1201,1040,857,753,713,567,493; HR-MS (FAB +): calculated value: C 10h 12auClN[M+H] +=378.0324, measured value: 378.0332.
Below the compound of listed example I X and X in the mode that is similar to example VII A I, prepare.
Example I X:[AuCl (2,6-diisopropyl phenyl isonitrile)]
Productive rate with 99% obtains title compound.
1h NMR (300MHz, CD 2cl 2): δ=1.24 (d, 12H, J=6.9Hz ,-CH 3), 3.2 (m, 2H, J=6.8Hz ,-CH-), 7.22 (d, 2H, J=7.9Hz, ArH), 7.45 (t, 1H, J=7.8Hz, ArH); 13c NMR (75MHz, CD 2cl 2): δ=22.75 (q, 4C), 30.43 (d, 2C), 124.42 (d, 3C), 132.06 (s, 2C), 146.87 (s); IR (KBr): ν=2946,2867,2208 (NC), 1632,1462,1385,1364,1261,1185,1109,1062,936,799,750,534; HR-MS (FAB +): calculated value: C 13h 17auN[M-Cl -] +=384.1027, measured value: 384.1030 embodiment X:[AuCl (tert-butyl isonitrile)]
Productive rate with 99% obtains title compound.The data of all analytical data and former report (R.Heathcote, J.A.S.Howell, N.Jennings, D.Cartlidge, L.Cobden, C.Coles, M.Hursthouse, Dalton Trans.2007,13,1309-1315) in full accord.
I.4 synthesize isonitrile-Pt (II) title complex
Universal program:
By [Pt (CH 3cN) 2cl 2] be dissolved in CHCl 3in and add suitable isonitrile.This mixture is stirred 12 hours under refluxing.Remove desolventizing and the gained colorless solid is washed with pentane, obtaining isonitrile-Pt (II) title complex.
Embodiment XI: cis-[PtCl 2(2,6-diisopropyl phenyl isonitrile) 2]
By [Pt (CH 3cN) 2cl 2] (272mg, 780 μ mol) be dissolved in CHCl 3(15ml) in and add 2,6-3,5-dimethylphenyl isonitrile (212mg, 1.60mmol).This mixture is stirred 12 hours under refluxing.Except desolventizing and by pentane washing (3 * 10ml) for the gained colorless solid, obtain title compound (489mg, 749 μ mol, 96%). 1h NMR (500MHz, CD 2cl 2): δ=1.25 (d, 12H, J=6.9Hz ,-CH 3), 3.29 (m, 2H, J=6.9Hz ,-CH-), 7.22 (d, 2H, J=7.8Hz, ArH), 7.42 (t, 1H, J=7.8Hz, ArH), 13c-NMR (125MHz, CD 2cl 2): δ=22.89 (q, 8C), 30.38 (d, 4C), 124.31 (d, 6C), 131.72 (s, 4C), 146.67 (s, 2C); IR (KBr): ν=2966,2929,2869,2219,2189,1475,1465,1457,1436,1386,1365,1184,1062,938,804,797,747,736,491cm -1; HR-MS (FAB +): m/z=604.2060, C 26h 34clN 2calculated value [the M-Cl of Pt -] +: 604.2058, m/z=569.2372, C 26h 34n 2calculated value [the M-2Cl of Pt -] +: 569.2370.
I.5 the 2-of general formula III (chloroethyl) ammonium chloride (Y=Cl)
Figure BDA00003115671900591
R 2, R 3, R 4, R 7and R 8have above-mentioned implication, DCM is methylene dichloride.
Synthesizing according to the document program of 2-(chloroethyl) ammonium chloride, A.Habtemariam for example, B.Watchman, B.S.Potter, R.Palmer, S.Parsons, A.Parkin, P.J.Sadler, J.Chem.Soc., Dalton Trans.2001,8,1306-1318 is started and is realized by commercially available amino alcohol.
I.6 synthesizing amino alcohol
Embodiment XII:2-(diamantane-1-base amino) ethanol
1-adamantanamines (1g, 6.05mmol) and ethylene iodohydrin (1.20g, 7.00mmol) are dissolved in benzonitrile (2ml).This mixture is heated 12 hours under 120 ° of C.After this precipitation is leached and carefully uses petroleum ether (3 * 20ml).Be dissolved in DCM (30ml) by white solid and use saturated Na 2cO 3solution washing (3 * 50ml).Organic layer is separated, use Na 2sO 4dry also removal of solvent under reduced pressure, obtain title compound (950mg, 4.86mmol, 80%) with water white oil.
1h NMR (250MHz, CD 2cl 2): δ=1.55 (m, 12H ,-CH 2-), 1.99 (bs, 5H ,-CH-and overlapping OH, NH), 2.65 (t, 2H, J=5Hz ,-CH 2-), 3.44 (t, 2H, J=5.1Hz ,-CH 2-); All spectroscopic datas and the former data of report, P.E.Aldrich for example, E.C.Herrmann, W.E.Meier, M.Paulshock, W.W.Prichard, J.A.Snyder, J.C.Watts, J.Med.Chem.1971,14,535-543 is in full accord.
I.7 N-(2, the 2-dimethoxy-ethyl) amine for preparing general formula V
Figure BDA00003115671900601
R 2, R 3, R 8, R 10and R 11there is above-mentioned implication.
In typical program, by 1 equivalent amine R 2nH 2be dissolved in methylene dichloride and add MgSO 4with 1.5 equivalent compounds (4).This mixture is at room temperature stirred 12 hours.Then leach MgSO 4and evaporating solvent.The analytical pure imines is used under further not purifying.Be dissolved in anhydrous methanol by the gained imines and add 2 equivalent NaBH under 0 ° of C 4.After removing ice bath, this mixture is stirred 2 hours again.This reaction water quencher, with the methylene dichloride dilution and by the saturated NH of organic phase 4cl solution and salt water washing.Crude product is by distillation or column chromatography (SiO 2) purify, obtain title compound.
Embodiment XIII:N-(2,2-dimethoxy-ethyl)-2，4，6-trimethyl aniline
Use the 2.50g (18.5mmol) in the 100ml methylene dichloride according to this universal program
Figure BDA00003115671900602
base amine, 3.2g (27.3mmol) 2,2-dimethoxy acetaldehyde (60% aqueous solution) and 3.00g MgSO 4prepare title compound.After filter solvents, with faint yellow solid, obtain N-(2,2-dimethoxy ethylidene)-2，4，6-trimethyl aniline; Productive rate: 4.05g (18.3mmol, 99%). 1h-NMR (300MHz, CDCl 3): δ=2.07 (s, 6H, CH 3), 2.24 (s, 3H, CH 3), 3.31 (s, 6H, OCH 3), 4.87 (d, J=4.5Hz, 1H, CH (OMe) 2), 6.83 (s, 2H, ArH), 7.42 (d, J=4.5Hz, 1H, CH=N); 13c-NMR (75MHz, CDCl 3): δ=18.31 (q, 2C), 20.79 (q), 54.32 (q, 2C), 103.61 (d), 125.82 (d, 2C), 128.87 (s, 2C), 133.52 (s), 147.53 (s), 163.5 (d); IR (KBr): ν=3431,2999,2955,2914,2836,1667,1480,1455,1442,1375,1308,1215,1194,1147,1098,1065,1004,983,849,782cm -1; HR-MS (EI +): m/z=221.1388, C 13h 19o 2the calculated value of N [M] +: 221.1416.
Under nitrogen atmosphere, N-(2,2-dimethoxy ethylidene)-2，4，6-trimethyl aniline (2.40g, 10.9mmol) is dissolved in the 50ml anhydrous methanol and adds 533mg NaBH 4(14.1mmol).Pass through distillation (120 ° of C, 6 * 10 after aftertreatment -2millibar) purifying crude product; Output: 2.12g (mmol, 87.1%); 1h-NMR (300MHz, CDCl 3): δ=2.27 (s, 3H, CH 3), 2.31 (s, 6H, CH 3), 3.12 (d, J=6.4Hz, 1H, CH (OMe) 2), 3.26 (bs, NH), 3.44 (s, 6H, OCH 3), 4.51 (t, J=6.4Hz, 2H, CH 2), 6.86 (s, 2H, ArH); 13c-NMR (75MHz, CDCl 3): δ=18.27 (q, 2C), 20.57 (q), 49.73 (t), 53.74 (q, 2C), 103.46 (t), 129.43 (d, 2C), 131.38 (q, 2C), 131.38 (d), 143.05 (s); IR (KBr): ν=3379,2936,2856,2832,1486,1447,1376,1306,1236,1194,1157,1131,1074,1034,977,924,854,739,564cm -1; HR-MS (EI +): m/z=223.1573, C 13h 21o 2the calculated value of N [M] +: 223.1572.
I.8 synthetic wherein EWG is CO (O) CH 3formula III b compound
Embodiment XIV:(E)-4-(cyclo-dodecyl amino) but-2-ene acid methyl esters
Under nitrogen atmosphere by (E)-4-bromine but-2-ene acid methyl esters (5.70g, 31.8mmol), cyclododecane amine (6.41g, 35.0mmol) and Cs 2cO 3be suspended in anhydrous tetrahydro furan (THF) (150.0ml) in.This mixture is heated 12 hours and adds NH under refluxing 4cl (saturated solution, 100ml).By DCM extraction for this mixture (three times, 50.0ml).Organic layer Na 2sO 4dry also removal of solvent under reduced pressure.Crude product is purified by the column chromatography that uses silicon-dioxide and petrol ether/ethyl acetate (4:1), with yellow solid, obtains title compound (5.54g, 19.7mmol, 62%). 1H NMR(300MHz，CD 2Cl 2)δ=1.07-1.54(m，23H，-CH 2-、-NH-)，2.67(m，1H，-CH-)，3.44(dd，J=5.4，2.2Hz，2H，-CH 2-)，3.75(s，3H，-CH 3)，6.02(dd，J=15.7，2.1Hz，1H，=CH-)，7.01(dq，J=15.7，5.2Hz，1H，=CH-)。
II. the NHC-of synthesis type I (transition metal) title complex
NHC-(transition metal) title complex of II.1 synthesis type I-A.2.1
II.1.1 synthesizes NHC-Pd (II) title complex
The universal program of synthetic NHC-Pd (II) title complex
In in typical program, cis-(isonitrile)-Pd (II) title complex (321 μ mol) and 2-(chloroethyl) ammonium chloride (350 μ mol) being suspended in to anhydrous THF.Add triethylamine (0.5ml, 6.81mmol).This mixture is stirred 12 hours at ambient temperature.Decompression is removed all volatile matters and solid is dissolved in DCM (20ml) after this.By the saturated NH of this solution 4cl solution (20ml) extraction.Organic layer Na 2sO 4dry also removal of solvent under reduced pressure.Crude product is dissolved in minimum DCM and with ether layer and covers, and this brings out NHC-Pd (II) title complex with the clear crystal crystallization.Crystal is leached, with ether washing drying under reduced pressure.All title complexs of below listing in the embodiment 1-15 in Table I are air and hydrostabile compound and can store at ambient temperature and not decompose.
Table I
Figure BDA00003115671900621
Figure BDA00003115671900622
The physical-chemical data of the title complex of embodiment 1-14 is listed as follows:
Embodiment 1:
1h NMR (300MHz, DMSO): δ=2.06 (s; 3H ,-CH 3), 2.30 (s; 6H ,-CH 3), 2.44 (s; 3H ,-CH 3), 3.52 (s; 3H ,-CH 3), 3.98 (m; 4H ,-CH 2-), 7.25 (m; 6H, ArH); 13c NMR (75MHz, DMSO): δ=17.35,17.93,18.68,37.20,51.05,51.20,128.31,128.42,128.93,129.06,130.68,135.33,135.62,136.77,137.71,182.03; IR (KBr): ν=3443,2951,2919,2195,1631,1541,1491,1473,1411,1383,1317,1276,1116,780,734,619; HRMS (FAB +) C 19h 25n 3clPd[M-Cl -] +: calculated value: 460.0772, measured value: 460.0763.
Embodiment 2:
1h NMR (600MHz, CD 2cl 2): δ=1.34 (d, 3H, J=6.8Hz ,-CH 3), 1.39 (d, 3H, J=6.7Hz ,-CH 3), 2.01 (s, 3H ,-CH 3), 2.27 (s, 6H ,-CH 3), 2.47 (s, 3H ,-CH 3), 3.82-3.91 (m, 4H ,-CH 2-), 5.40 (m, 1H, J=6.9,6.3Hz ,-CH-), 6.94 (dd, 1H, J=7.3,1.9Hz, ArH), 7.1 (d, 2H, J=7.6Hz, ArH), 7.17-7.27 (m, 3H, ArH); 13c NMR (125MHz, CD 2cl 2): δ=18.11,18.92,19.40,20.13,20.93,43.61,51.02,52.25,128.65,128.70,129.62,130.01,130.70,135.64,136.19,137.30,138.70,184.22; 15n NMR (600MHz, CD 2cl 2, urea): δ=131.78,148.43,171.32; IR (KBr): ν=2970,2925,2358,2195 (NC), 1633,1509,1467,1368,1314,1271,1192,1127,1102,1056,935,782,623,602,569; HR-MS (FAB +): calculated value: C 23h 29clN 3pd[M-Cl -] +=488.1085, measured value: 488.1104.
Embodiment 3:
1h NMR (300MHz, CD 2cl 2): δ=0.98-1.86 (m, 10H ,-CH 2-), 1.98 (s, 3H ,-CH 3), 2.23 (s, 6H ,-CH 3), 2.44 (s, 3H ,-CH 3), 3.81 (m, 4H ,-CH 2-), 4.87 (tt, 1H, J=10.7,3.8Hz ,-CH-) 6.9 (dd, 1H, J=6.6Hz, ArH), 7.07 (d, 2H, J=8.4Hz, ArH), 7.12 (m, 3H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=18.49,19.23,19.80,25.91,26.04,26.12,31.18,32.07,45.24,51.33,60.10,129.02,129.06,129.99,130.38,131.05,136.04,136.57,139.11,184.56; IR (KBr): ν=2931,2855,2193 (NC), 1632,1510,1454,1380,1333,1300,1272,1170,1100,1032,990,894,780,623,570; HR-MS (FAB +): calculated value: C 26h 33clN 3pd[M-Cl -] +=530.1398, measured value: 530.1397.
Embodiment 4:
(non-enantiomer mixture) 1h NMR (300MHz, CD 2cl 2): δ=1.05-1.81 (m, 10H ,-CH 2), 1.92 (s ,-CH 3), 2.06 (s ,-CH 3), 2.17 (s ,-CH 3), 2.39 (s ,-CH 3), 2.55 (s, CH 3), 4.03 (dd, J=11.3,5.6Hz ,-CH 2), 4.15 (dd, J=11.3,6.0Hz ,-CH 2), 4.33 (t, J=11.3Hz ,-CH 2), 4.88 (dd, J=11.8,5.6Hz ,-CH-), 5.03 (dd, J=11.6,6.0Hz ,-CH-), 5.16 (m, 1H ,-CH-), 6.73 (m, 1H, ArH), 6.96-7.32 (m, 10H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=18.27,18.51,18.81,19.08,19.71,19.87,25.10,25.44,25.48,30.24,30.75,31.38,31.77,50.75,52.29,59.58,59.99,66.51,66.56,77.44,127.98,128.01,128.30,128.49,129.07,129.20,129.27,129.57,129.68,129.90,130.36,130.45,183.36,183.98; IR (KBr): ν=3031,2932,2855,2193,1631,1509,1474,1453,1416,1382,1296,1250,1210,1168,1101,1034,998,780,701; HR-MS (FAB +): calculated value: C 32h 37clN 3pd[M-Cl -] +=604.1711, measured value: 604.1722
Embodiment 5:
1h NMR (300MHz, CD 2cl 2): δ=1.32 (d, 3H, J=6.9Hz ,-CH 3), 1.37 (d, 3H, J=6.6Hz ,-CH 3), 1.95 (s, 3H ,-CH 3), 2.22 (s, 6H ,-CH 3), 2.25 (s, 3H ,-CH 3), 2.26 (s, 3H ,-CH 3), 2.41 (s, 3H ,-CH 3), 3.71-3.92 (m, 4H ,-CH 2-), 5.38 (m, 1H, J=6.8Hz ,-CH-), 6.73 (s, 1H, ArH), 6.90 (s, 2H, ArH), 7.00 (s, 1H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=18.37,19.14,19.67,20.50,21.27,21.58,21.88,43.86,51.42,52.53,58.95,129.69,129.75,131.02,135.09,135.56,136.25,138.54,139.96,141.77,184.74; IR (KBr): ν=2971,2193,1608,1510,1458,1382,1314,1271,1197,1105,1058,855,713,625,599,573,460,428; HR-MS (FAB +): calculated value: C 25h 33clN 3pd[M-Cl -] +=516.1398, measured value: 516.1391
Embodiment 6:
1h NMR (300MHz, CD 2cl 2): δ=1.05 (d, 3H, J=3.3Hz ,-CH 3), 1.07 (d, 3H, J=3.4Hz ,-CH 3), 1.13 (d, 3H, J=7.0Hz ,-CH 3), 1.19 (d, 6H, J=6.8Hz ,-CH 3), 1.21 (d, 6H, J=6.8Hz ,-CH 3), 2.88 (m, 1H, J=6.8Hz ,-CH-), 3.24 (m, 3H ,-CH-), 3.71-4.01 (m, 4H ,-CH 2-), 5.47 (dm, 1H, J=7.0,6.6Hz ,-CH-), 7.18,7.17 (dd, 1H, J=7.7,1.4Hz, ArH), 7.19 (d, 2H, J=7.7Hz, ArH), 7.29 (dd, 1H, J=7.8,1.7Hz, ArH), 7.40 (m, 2H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=20.65,21.17,23.49,23.63,23.87,24.51,27.22,27.26,29.29,29.54,30.36,43.67,53.03,124.73,125.01,126.19,130.76,131.80,134.57,146.85,146.96,149.31,185.97; IR (KBr): ν=2965,2930,2870,2185,1497,1459,1433,1386,1366,1348,1331,1315,1267,1184,1113,1058,806,751,628; HR-MS (FAB +): calculated value: C 31h 45clN 3pd[M-Cl -] +=600.2337, measured value: 600.2335
Embodiment 7:
1h NMR (500MHz, CD 2cl 2): δ=1.03 (d, 3H, J=6.9Hz ,-CH 3), 1.04 (d, 3H, J=6.9Hz ,-CH 3), 1.11 (d, 3H, J=6.9Hz ,-CH 3), 1.17 (d, 6H, J=6.8Hz ,-CH 3), 1.20 (d, 6H, J=6.8Hz ,-CH 3), 1.34 (d, 3H, J=6.7Hz ,-CH 3), 1.42-1.73 (m, 6H ,-CH 2-), 1.85 (m, 3H ,-CH 2-), 2.86 (m, 1H, J=6.8Hz ,-CH-), 3.21 (m, 2H, J=6.9Hz ,-CH-), 3.27 (m, 1H ,-CH-), (4.93 tt, 1H, J=11.4,3.7Hz ,-CH-), 7.15 (dd, 1H, J=7.7,1.3Hz, ArH), 7.18 (d, 2H, J=7.9Hz, ArH), 7.28 (dd, 1H, J=7.8,1.4Hz, ArH), 7.39 (td, 2H, J=7.8,2.1Hz, ArH); 13c NMR (75MHz, CD 2cl 2): δ=20.65,21.17,23.49,23.63,23.87,24.51,27.22,27.26,29.29,29.54,30.36,43.69,53.03,124.73,125.01,126.19,130.76,131.80,134.57,146.85,146.96,149.31,185.97; IR (KBr): ν=2963,2931,2867,2188,1589,1500,1458,1386,1365,1336,1304,1269,1184,1111,1055,804,750,731,626; HR-MS (FAB +): calculated value: C 34h 49clN 3pd[M-Cl -] +=640.2650, measured value: 640.2672
Embodiment 8:
1h NMR (300MHz, CDCl 3): δ=1.0 (d, 3H, J=6.8Hz ,-CH 3), 1.02 (d, 3H, J=6.9Hz ,-CH 3), 1.07 (d, 3H, J=6.9Hz ,-CH 3), 1.17 (d, 6H, J=6.9Hz ,-CH 3), 1.19 (d, 6H, J=6.9Hz ,-CH 3), 1.4 (d, 3H, J=6.4Hz ,-CH 3), 1.69 (m, 6H ,-CH 2-), 2.23 (m, 3H ,-CH-), 2.43 (m, 3H ,-CH-,-CH 2-), 2.74 (m, 3H ,-CH-,-CH 2-), 2.86 (m, 1H, J=6.8Hz ,-CH-), 3.24 (m, 2H, J=6.8Hz ,-CH-), 3.36 (m, 1H ,-CH-), 3.66-4.01 (m, 4H ,-CH 2-), 7.06 (dd, 1H, J=7.7,1.6Hz, ArH), 7.12 (d, 2H, J=7.8Hz, ArH), 7.25 (dd, 1H, J=7.8,1.8Hz, ArH), 7.33 (td, 2H, J=7.9,2.8Hz, ArH); 13c NMR (75MHz, CDCl 3): δ=23.09,23.33,23.57,24.14,27.01,27.10,28.94,29.16,29.75,30.02,36.12,42.96,45.90,52.74,59.42,124.04,124.06,125.93,130.17,131.02,135.49,145.74,146.33,148.95,184.88; IR (KBr): ν=2965,2911,2869,2186,1630,1478,1456,1386,1363,1330,1305,1256,1190,1100,1056,804,751,620; HR-MS (FAB +): calculated value: C 38h 53clN 3pd[M-Cl -] +=692.2963, measured value: 692.2974
Embodiment 9:
(non-enantiomer mixture), 1h NMR (300MHz, CD 2cl 2): δ=-0.14 (d, J=6.6Hz ,-CH 3) ,-0.06 (d, J=6.8Hz ,-CH 3), 0.79 (d, J=6.8Hz ,-CH 3), 1.06-1.99 (m, 29H), 1.56-3.11 (m, 3H ,-CH 2-), 3.44 (m, J=6.6Hz ,-CH-), 3.87 (dd, J=11.4,4.0Hz ,-CH 2-), 4.01 (m ,-CH 2-), 4.36 (m ,-CH 2-), 4.88 (dd, J=11.2,4.0Hz ,-CH-), 5.11 (m ,-CH-), 6.97-7.45 (m, 11H, ArH), 13c NMR (75MHz, CD 2cl 2): δ=22.46, 22.80, 23.54, 23.62, 23.85, 24.51, 24.73, 25.00, 25.50, 25.58, 25.77, 26.49, 26.79, 26.90, 28.87, 28.96, 29.26, 29.42, 30.01, 30.11, 30.25, 30.81, 31.58, 31.79, 46.15, 52.14, 60.20, 60.68, 68.09, 68.79, 123.97, 124.27, 124.44, 124.62, 124.98, 125.88, 126.28, 128.09, 128.27, 129.64, 129.75, 129.85, 131.16, 131.47, 133.04, 134.34, 139.45, 140.07, 145.68, 145.78, 146.94, 147.27, 147.70, 150.06, 184.67, 186.02, IR (KBr): ν=2943,2858,2195,1631,1512,1486,1473,1443,1381,1354,1307,1273,1253,1168,1143,1096,1011,779,632, HR-MS (FAB +): calculated value: C 40h 53clN 3pd[M-Cl -] +=716.2963, measured value: 716.3002
Embodiment 10:
1h NMR (300MHz, CDCl 3): δ=1.49 (s, 9H, CH 3), 1.71 (s, 9H, CH 3), 3.57 (s, 3H, CH 3), 3.73 (m, 4H, CH 2); 13c NMR (75MHz, CDCl 3): δ=30.23,30.72,39.22,47.71,50.57,53.64,56.97,77.65,183.1; IR (KBr): ν=3444,2980,2218,1630,1530,1466,1371,1324,1287,1200,1136,620; HRMS (FAB +) C 13h 24n 3pd[M-HCl 2] +: calculated value: 328.1011, measured value: 328.1005
Embodiment 11:
1h NMR (300MHz, CD 2cl 2): δ=1.19 (d, 3H, J=6.8Hz ,-CH 3), 1.26 (d, 3H, J=6.7Hz ,-CH 3), 1.45 (s, 9H ,-CH 3), 1.65 (s, 9H ,-CH 3), 3.38-3.79 (m, 4H ,-CH 2-), 5.56 (m, 1H, J=6.7Hz ,-CH-); 13c NMR (75MHz, CD 2cl 2): δ=18.55,19.27,29.01,29.44,40.68,46.02,52.17,55.79; IR (KBr): ν=2979,2936,2876,2217,1635,1504,1454,1400,1369,1322,1285,1235,1197,1111,806,622,594,523; HR-MS (FAB +): calculated value: C 15h 29clN 3pd[M-Cl -] +=392.1085, measured value: 392.1074
Embodiment 12:
1h NMR (300MHz, CD 2cl 2): δ=0.98-2.12 (m, 10H ,-CH 2-), 1.45 (s, 9H ,-CH 3), 1.66 (s, 9H ,-CH 3), 3.39-3.77 (m, 4H ,-CH 2-), 5.06 (m, 1H ,-CH-); 13c NMR (75MHz, CD 2cl 2): δ=24.42,24.53,29.00,29.14,29.45,30.07,41.97,45.97,55.83,59.82,179.92; IR (KBr): ν=2918,2933,2856,2216,1631,1502,1451,1371,1313,1283,1263,1247,1225,1195,1088,1031,804,622; HR-MS (FAB +): calculated value: C 18h 33clN 3pd[M-Cl -] +=432.1398, measured value: 432.1410
Embodiment 13:
1h NMR (300MHz, CDCl 3): δ=2.35 (s, 3H, CH 3), 2.58 (s, 3H, CH 3), 3.66 (s, 3H, CH 3), 4.02 (m, 4H, CH 2), 7.14 (m, 1H, ArH), 7.19 (m, 1H, ArH), 7.27 (m, 2H, ArH), 7.30 (m, 2H, ArH) ppm; 13c NMR (75MHz, CDCl 3): δ=19.37,19.75,38.20,50.94,52.10,77.45,127.56,127.74,129.31,130.62,130.99,131.03,131.13,133.06,135.22,138.96,141.41,186.60; IR (KBr): ν=3431,2202,1632,1549,1487,1458,1413,1319,1273,1114,781,730,617; HRMS (FAB +) C 19h 19n 3cl 3pd[M-Cl -] +: calculated value: 499.9679, measured value: 499.9636
Embodiment 14:
(non-enantiomer mixture); 1h NMR (500MHz, CDCl 3): δ=1.45-2.02 (m; 8H, CH 2), 2.01 (s ,-CH 3), 2.03 (s ,-CH 3), 2.27 (s ,-CH 3), 2.29 (s ,-CH 3), 2.52 (s ,-CH 3), 2.54 (s ,-CH 3), 3.32 (td, J=12.7,3.3Hz ,-CH 2-), 5.07 (m ,-CH 2-), 5.14 (m ,-CH 2-), 6.85-6.91 (m, ArH), 7.08-7.10 (m, ArH), 7.16-7.26 (m, ArH); IR (KBr): ν=2939,2856,2196,1631,1519,1443,1381,1307,1273,1254,782,631,577; HRMS (FAB +) C 24h 29n 3clPd[M-HCl] +: calculated value: 500.1085, measured value: 500.1060
Embodiment 15:
(non-enantiomer mixture, main isomer); 1h NMR (500MHz, CDCl 3): δ=0.00 (d, J=6.6Hz, 3H ,-CH 3), 0.88 (d, J=6.6Hz, 3H ,-CH 3), 1.09 (d, J=6.6Hz, 6H ,-CH 3), 1.09 (d, J=6.6Hz, 6H ,-CH 3), 1.26-1.73 (m, 25H ,-CH 2-), 1.59 (d, J=6.6Hz, 6H ,-CH 3), 1.68 (m, 2H ,-CH 2-), 1.97 (m, 1H ,-CH 2-), 2.22 (m, 1H ,-CH 2-), 2.59 (m, J=6.6Hz, 2H ,-CH-), 2.84 (m, J=6.6Hz, 1H ,-CH-), 3.54 (m, 1H ,-CH-), 3.83 (m, 1H ,-CH 2-), 4.29 (m, 1H ,-CH 2-), 4.83 (m, 1H ,-CH-), 5.24 (m, 1H ,-CH-), 6.99 (d, J=7.7Hz, 1H, ArH), 7.05 (d, J=7.7Hz, 2H, ArH), 7.17 (d, J=7.7Hz, 1H, ArH), 7.25-7.33 (m, 5H, ArH), (7.37 d, J=6.8Hz, 2H, ArH); 13c NMR (125MHz, CDCl 3): δ=22.83 (2C), 23.09 (2C), 23.67,24.60,25.36 (2C), 26.52,26.58,26.72 (2C), 26.94 (2C), 27.07,27.08,27.11,27.22,27.45 (2C), 28.71,28.80,29.65 (2C), 30.83,32.50,52.72,60.84,68.75,123.50 (2C), 124.11,126.06,128.04 (2C), 129.54,129.56 (2C), 129.61,130.74,134.22,139.64,145.34,145.51 (2C), 140.34,186.39.
II.1.2 synthesizes NHC-Au (I) title complex
The universal program of synthetic NHC-Au (I) title complex
In typical program, (isonitrile)-Au (I) title complex (132 μ mol) and 2-(chloroethyl) ammonium chloride (396 μ mol) are suspended in anhydrous DCM.Add triethylamine (0.5ml, 6.81mmol).This mixture is stirred 96 hours at ambient temperature.Decompression is removed all volatile matters and solid is dissolved in DCM (10ml) after this.By the saturated NH of this solution 4cl solution (20ml) extraction.Organic layer Na 2sO 4dry also removal of solvent under reduced pressure.Crude product is by column chromatography (SiO 2, the mixture of sherwood oil and ethyl acetate; Embodiment 15 and 18: petrol ether/ethyl acetate, 2/1; Embodiment 16: petrol ether/ethyl acetate, 5/1 and embodiment 17: petrol ether/ethyl acetate, 1/1) purify.Below in Table II, all title complexs of listed embodiment 15-18 are air and hydrostabile compound and can store at ambient temperature and not decompose.
Table II
Figure BDA00003115671900681
Embodiment R 1 R 3 R 2 R 7 Productive rate/material performance
16 2,4,6-trimethylphenyl H Sec.-propyl H 45%, colorless solid
17 2,4,6-trimethylphenyl H The 1-adamantyl H 50%, colorless solid
18 2,6-diisopropyl phenyl H Sec.-propyl H 80%0, colorless solid
19 The tertiary butyl H Sec.-propyl H 80%0, colourless solid stopping
The physical-chemical data of the title complex of embodiment 16-19 is listed as follows:
Embodiment 16:
R f(petrol ether/ethyl acetate 2/1)=0.28; 1h NMR (300MHz, CD 2cl 2): δ=1.28 (d, 6H, J=6.8Hz ,-CH 3), 2.17 (s, 6H ,-CH 3), 1.26 (s, 3H ,-CH 3), 3.72 (s, 4H ,-CH 2-), 4.79 (m, 1H, J=6.8Hz ,-CH-), 6.92 (s, 2H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=17.01,19.63,20.09,42.34,49.34,50.89,128.68,134.64,135.19,138.03,191.54; IR (KBr): ν=2968,1609,1506,1456,1369,1344,1322,1276,1263,1202,1161,1099,1058,1021,862,804,613,604,582; HR-MS (FAB +): calculated value: C 15h 23clN 2au[M+H +] +=463.1215, measured value: 463.1194
Embodiment 17:
R f(petrol ether/ethyl acetate 5/1)=0.22; 1h NMR (500MHz, CD 2cl 2): δ=1.69 (s, 6H), 2.16 (s, 9H), 2.26 (s, 3H), 2.38 (s, 6H), 3.60 (m, 2H ,-CH 2-), 3.89 (m, 2H ,-CH 2-), 6.92 (s, 2H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=18.17,21.27,30.42,36.37,43.75,46.86,49.30,57.43,129.79,136.12,137.20,139.01,192.76; IR (KBr): ν=2909,2851,1631,1543,1494,1449,1360,1312,1272,1192,1142,1103,1036,852,817,674,607,581
Embodiment 18:
1h NMR (300MHz, CD 2cl 2): δ=1.19 (d, 6H, J=7.0Hz ,-CH 3), 1.29 (d, 12H, J=6.8Hz ,-CH 3), 2.86 (m, 2H, J=6.9Hz ,-CH-), 3.74 (s, 4H ,-CH 2-), 4.81 (m, 1H, J=6.8Hz ,-CH-), 7.19 (d, 2H, J=7.8Hz, ArH), 7.38 (m, 1H, ArH); 13c NMR (75MHz, CD 2cl 2): δ=19.67,23.31,23.91,27.72,42.34,50.92,51.98,123.74.128.89,134.09,146.23,192.18; 15nNMR (600MHz, CD 2cl 2, urea): δ=130.29,146.50; IR (KBr): ν=2964,2926,2867,1631,1502,1460,1385,1367,1318,1274,1236,1192,1163,1111,1059,1019,808,763,601; HR-MS (FAB +): calculated value: C 18h 29clN 2au[M+H +] +=505.1685, measured value: 505.1652
Buy and execute example 19:
R f(petrol ether/ethyl acetate 2/1)=0.18; 1h NMR (300MHz, CD 2cl 2): δ=1.19 (d, 6H, J=6.8Hz;-CH 3), 1.57 (s, 9H ,-CH 3), 3.4 (dd, J=11.4,8.9Hz ,-CH 2), 3.64 (dd, J=11.4,8.9Hz ,-CH 2), 4.88 (m, J=6.8Hz ,-CH-); 13c NMR (125MHz, CD 2cl 2): δ=20.61,30.92,41.92,47.40,53.65,56.06,191.32; IR (KBr): v=2968,2875,1494,1450,1397,1366,1328,1282,1235,1202,1117,955,711,676,610,521,436; HR-MS (FAB +): calculated value: C 10h 21clN 2au[M+H +] +=401.1059, buy measured value: 401.1005
II.1.3 synthesizes the universal program of NHC-Pt (II) title complex
In typical program, cis-(isonitrile)-Pt (II) title complex (156 μ mol) and 2-(chloroethyl) ammonium chloride (200 μ mol) are suspended in anhydrous DCM.Add triethylamine (0.25ml, 3.4mmol).This mixture is stirred 72 hours at ambient temperature.Decompression is removed all volatile matters and solid is dissolved in DCM (10ml) after this.By the saturated NH of this solution 4cl solution (20ml) extraction.Organic layer Na 2sO 4dry also removal of solvent under reduced pressure.Below in Table III, listed embodiment 19 and all title complexs of 20 are air and hydrostabile compound and can store at ambient temperature and not decompose.
Table III
(I_A.2.1), wherein M is PdCl 2(CNR 1)
Embodiment R 1 R 3 R 2 R 7 Productive rate/material performance
20 2,6-diisopropyl phenyl H Sec.-propyl H 63%, colorless solid
21 2,6-diisopropyl phenyl H Cyclohexyl H 70%, colorless solid
The physical-chemical data of embodiment 20 and 21 title complex is listed as follows:
Embodiment 20:
1h NMR (500MHz, CD 2cl 2): δ=1.04 (d, 3H, J=6.7Hz ,-CH 3), 1.06 (d, 3H, J=6.7Hz ,-CH 3), 1.13 (d, 3H, J=6.7Hz ,-CH 3), 1.19 (d, 6H, J=6.9Hz ,-CH 3), 1.2 (d, 6H, J=6.9Hz ,-CH 3), 1.34 (d, 6H, J=6.6Hz ,-CH 3), 1.43 (d, 3H, J=6.7Hz ,-CH 3), 2.88 (m, 1H, J=6.7Hz ,-CH-), 3.24 (m, 3H ,-CH-), 3.72-3.98 (m, 4H ,-CH 2-), 5.50 (m, 1H, J=6.6Hz ,-CH-), 7.16 (m, 3H, ArH), 7.27 (d, 1H, J=7.6Hz, ArH), 7.39 (m, 2H, ArH); 13c NMR (125MHz, CD 2cl 2): δ=20.24,20.58,23.03,23.11,23.47,23.93,26.74,26.88,28.89,29.23,29.92,43.24,52.24,124.23,124.60,125.63,130.19,130.68,134.68,146.15,146.47,148.62,173.14; 195pt NMR (498MHz, CD 2cl 2, Na 2ptCl 4): δ=-3669.80; HR-MS (FAB +): calculated value: C 31h 45cl 2n 3pt[M-Cl -] +=689.2950, measured value: 689.2914.
Embodiment 21:
1h NMR (600MHz, CD 2cl 2): δ=1.08 (d, 3H, J=6.8Hz ,-CH 3), 1.10 (d, 3H, J=6.8Hz ,-CH 3), 1.17 (d, 3H, J=6.8Hz ,-CH 3), 1.23 (d, 6H, J=6.8Hz ,-CH 3), 1.25 (d, 6H, J=6.8Hz ,-CH 3), 1.36 (t, 1H, J=7.3Hz ,-CH 2-), 1.38 (d, 3H, J=6.8Hz ,-CH 3), 1.46-1.58 (m, 3H ,-CH 2-), 1.67 (qd, 1H, J=12.1,3.2Hz, CH 3), 1.74 (d, 1H, J=14.3Hz ,-CH 2-), 1.91 (t, 3H, J=14.3Hz ,-CH 2-), 2.34 (m, 1H ,-CH 2-), 2.93 (m, 1H, J=6.8Hz ,-CH-), 3.26 (m, 2H, J=6.8Hz ,-CH-), 3.32 (m, 1H, J=6.8Hz ,-CH-), 3.79-4.03 (m, 4H ,-CH 2-), 5.00-5.06 (m, 1H ,-CH-), 7.20 (dd, 1H, J=7.8,1.4Hz, ArH), (7.22 d, 2H, J=7.8, ArH), 7.32 (dd, 1H, J=7.8,1.4Hz, ArH), (7.43 t, 1H, J=7.8, ArH), 7.44 (t, 1H, J=7.8, ArH); 13c NMR (150MHz, CD 2cl 2): δ=22.81,22.92,23.38,23.75,25.41,25.50,25.68,26.57,26.70,28.70,29.05,29.79,30.55,31.36,44.35,45.99,59.68,124.06,124,30,124.41,125.44,129.98,130.49,134.59,145.93,146.29,148.44,172.84; HR-MS (FAB +): calculated value: C 34h 49cl 2n 3pt[M-Cl -] +=729.3263, measured value: 729.3265.
II.2. the NHC-of synthesis type I-B.2.1 (transition metal) title complex
II.2.1 synthesizes Au (I)-NHC title complex
Universal program:
Figure BDA00003115671900721
Under nitrogen atmosphere and envrionment temperature, (tetramethylene sulfide) AuCl (1.00 equivalents, 50.0 μ mol) is dissolved in anhydrous DCM (0.10M).Add described isonitrile (1.05 equivalent) and by this solution stirring 5 minutes.Add after this described amine (1.50 equivalent) and continue and stir 36 hours.Under reduced pressure except desolventizing and by the gained crude product with cold pentane wash (5 times, 2ml).By the product drying under reduced pressure.Perhaps, can be by use the column chromatography purification compound of the mixture of sherwood oil and ethyl acetate on alkaline alumina.
Embodiment 22:(1-cyclohexyl-3-(2,6-diisopropyl phenyl) tetrahydroglyoxaline-4-ketone-2-subunit) gold trichloride (I)
Figure BDA00003115671900722
1h NMR (500MHz, CDCl 3/ C 6d 6/ 4/1): δ=1.08 (d, J=6.9Hz, 6H ,-CH 3), 1.24 (d, J=6.9Hz, 6H ,-CH 3), 1.42 (m, 5H ,-CH 2-), 1.68 (m, 1H ,-CH 2-), 1.82 (m, 2H ,-CH 2-), 1.97 (m, 2H ,-CH 2-), 2.51 (m, J=6.9Hz, 2H ,-CH-), 3.94 (s, 2H ,-CH 2-, the Cabbeen skeleton), 4.44 (m, 1H ,-CH-), 7.16 (d, J=7.8Hz, 2H, ArH), 7.37 (t, J=7.8Hz, 1H, ArH); 13c NMR (125MHz, CDCl 3/ C 6d 64/1): δ=24.26,24.28,24.97,25.10,29.50,31.99,48.59,63.29,124.73,129.24,131.22,146.29,171.84,201.85.
Embodiment 23:(1-cyclo-dodecyl-3-(2,6-diisopropyl phenyl) tetrahydroglyoxaline-4-ketone-2-subunit) gold trichloride (I)
Figure BDA00003115671900723
1h NMR (250MHz, CDCl 3): δ=1.13 (d, J=6.9Hz, 6H ,-CH 3), 1.21 (d, J=6.9Hz, 6H ,-CH 3), 1.18-1.71 (m, 20H ,-CH 2-), 1.94 (m, 2H ,-CH 2-), 2.57 (m, J=6.9Hz, 2H ,-CH-), 4.06 (s, 2H ,-CH 2-, the Cabbeen skeleton), 4.9 (m, 1H ,-CH-), 7.22 (d, J=7.7Hz, 2H, ArH), 7.44 (t, J=7.7Hz, 1H, ArH).
Embodiment 24:(3-(2,6-diisopropyl phenyl)-1-(1-phenylethyl) tetrahydroglyoxaline-4-ketone-2-subunit) gold trichloride (I)
Figure BDA00003115671900731
1h NMR (250MHz, CDCl 3): δ=1.03 (d, J=6.9Hz, 3H ,-CH 3), 1.10 (d, J=6.9Hz, 3H ,-CH 3), 1.27 (d, J=6.9Hz, 2H ,-CH 3), 1.29 (d, J=6.9Hz, 3H ,-CH 3), 1.81 (d, J=7.2Hz, 3H ,-CH 3), 2.43 (m, J=6.9Hz, 2H ,-CH-), 3.65 (d, J=21.2Hz, 1H ,-CH 2-, the Cabbeen skeleton), 4.03 (d, J=21.2Hz, 1H ,-CH 2-, the Cabbeen skeleton), 6.06 (q, J=7.2Hz, 3H ,-CH-), 7.2 (m, 8H, ArH).
II.2.2 synthesizes Pd (II)-NHC title complex
The universal program of the Pd of synthesis type I-B.2.1 (II)-NHC title complex
Figure BDA00003115671900732
Under nitrogen atmosphere and envrionment temperature, described palladium two (isonitrile) title complex (1.00 equivalents, 50.0 μ mol) is dissolved in anhydrous THF (0.30M).Add after this described amine (1.10 equivalent) and continue and stir 7 days.Under reduced pressure except desolventizing and by the gained crude product with cold pentane wash (5 times, 2.00ml).This product be dissolved in the DCM of minimum and add cold pentane to bring out the precipitation of Pd (II)-NHC title complex.
Embodiment 25:R 1=2,6-di-isopropyl, R 2the formula I-B.2.1 compound of=cyclohexyl
Figure BDA00003115671900741
1h NMR (250MHz, CDCl 3): δ=0.93 (d, J=6.8Hz, 3H ,-CH 3), 0.96 (d, J=6.8Hz, 3H ,-CH 3), 1.04 (d, J=6.8Hz, 3H ,-CH 3), 1.19 (d, J=6.8Hz, 6H ,-CH 3), 1.21 (d, J=6.8Hz, 6H ,-CH 3), 1.4 (d, J=6.8Hz, 3H ,-CH 3), 1.10-2.05 (m, 10H ,-CH 2-), 2.54 (m, 1H ,-CH-), 3.13 (m, 3H ,-CH-), 4.32 (m, 2H, Cabbeen skeletons), 5.22 (m, 1H ,-CH-), 7.17 (m, 2H, ArH), 7.44 (m, 4H, ArH).
By by DCM/ sherwood oil recrystallization title compound, obtain following formula: compound:
Figure BDA00003115671900742
II.3. the NHC-of synthesis type I-C.2.1 (transition metal) title complex
The general of II.3.1Au (I)-NHC title complex synthesizes
Under nitrogen atmosphere by described tetrahydroglyoxaline-4-ketone-2-subunit) gold trichloride (I) title complex (50.0mg, 77.6 μ mol, 1 equivalent) is dissolved in anhydrous THF.This mixture is cooled to-78 ° of C and adds two (trimethyl silyl) Lithamide (0.14M, in THF, 610 μ l, 1.1 equivalents).This mixture is stirred 30 minutes under-78 ° of C, then add this electrophilic reagent (1.1 equivalent).Making this mixture be warmed to envrionment temperature and continue stirs 30 minutes.After this, except desolventizing and by pentane washing for the gained crude product (3 times, 3ml).Product is dissolved in anhydrous DCM and the filtration over celite pad to remove LiCl.Removal of solvent under reduced pressure also stores the gained solid under nitrogen atmosphere under-32 ° of C.
Embodiment 26:(4-((t-butyldiphenylsilyl) oxygen base)-1-cyclo-dodecyl-3-(2,6-diisopropyl phenyl) imidazoles-2-subunit) gold trichloride (I)
Figure BDA00003115671900751
According to this universal program, use tert-butyl diphenyl chlorosilane to prepare title compound as electrophilic reagent.
1H NMR(250MHz，CD 2Cl 2)：δ=0.85(s，9H，-CH 3)，1.09(d，J=6.9Hz，6H，-CH 3)，1.26(d，J=6.9Hz，6H，-CH 3)，0.95-1.79(m，22H，-CH 2-)，2.42(m，J=6.9Hz，2H，-CH-)，4.63(m，J=6.8Hz，1H，-CH-)，5.59(s，1H，=CH)，7.31(m，6H，ArH)，7.45(m，7H，ArH)。
Embodiment 27:(4-(benzoyloxy)-1-cyclo-dodecyl-3-(2,6-diisopropyl phenyl)-imidazoles-2-subunit) gold trichloride (I)
Figure BDA00003115671900752
According to this universal program, use Benzoyl chloride to prepare title compound as electrophilic reagent.
1H NMR(250MHz，C 6D 6)：δ=0.98(d，J=6.8Hz，6H，-CH 3)，1.33(d，J=6.8Hz，6H，-CH 3)，1.05-1.92(m，22H，-CH 2-)，2.62(m，J=6.8Hz，2H，-CH-)，5.17(m，J=6.5Hz，1H，-CH-)，6.76(t，J=7.7Hz，2H，ArH)，6.91(t，J=7.5Hz，1H，ArH)，7.03(d，J=7.7Hz，2H，ArH)，7.19(m，2H，ArH，=CH)，7.68(m，2H，ArH)。
Embodiment 28:(4-((((4,5-dimethoxy-2-nitrobenzyl) oxygen base) carbonyl) oxygen base)-1-cyclo-dodecyl-3-(2,6-diisopropyl phenyl)-imidazoles-2-subunit) gold trichloride (I)
Figure BDA00003115671900761
According to universal program, use chloroformic acid 4,5-dimethoxy-2-nitrobenzyl ester prepares title compound as electrophilic reagent.
1H NMR(250MHz，CDCl 3)：δ=1.05(d，J=6.8Hz，6H，-CH 3)，1.26(d，J=6.8Hz，6H，-CH 3)，1.02-1.88(m，22H，-CH 2-)，2.32(m，J=6.8Hz，2H，-CH-)，3.83(s，3H，-CH 3)，3.93(s，3H，-CH 3)，5.58(s，2H，-CH 2-)，6.79(s，1H，=CH)，7.16(s，1H，ArH)，7.2(d，J=7.8Hz，2H，ArH)，7.44(t，J=7.8Hz，1H，ArH)，7.68(s，1H，ArH)。
The catalytic activity of III Pd (II)-NHC title complex
The universal program of III.1Suzuki-Miyaura reaction
Figure BDA00003115671900762
X=Cl or Br
The Pd catalyzer of [Pd]=formula I-A.2.1
Depend on the phenyl-halide as substrate, there are two kinds of programs in this reaction.
Chlorobenzene is as the program of substrate
Under nitrogen atmosphere, by the Pd (II) of embodiment 1,2,3,4,5,6,7,8,9,10,11,12,13 or 14-NHC title complex [1mol%], 2,5-dimethyl benzene ylboronic acid (1.20mmol) and chlorobenzene (1.00mmol) are dissolved in ethanol (2ml).This mixture is stirred 5 minutes and adds alkali potassium tert.-butoxide (1.00mmol).By this solution stirring 12 hours.Measure productive rate by using dodecane (1.00mmol) as interior target GC.The results are summarized in Table IV.
Bromobenzene is as the program of substrate
Under nitrogen atmosphere, by the Pd (II) of embodiment 1,2,3,4,5,6,7,8,9,10,11,12,13 or 14-NHC title complex [0.1mol%], 2,5-dimethyl benzene ylboronic acid (2.40mmol) and bromobenzene (2.00mmol) are dissolved in ethanol (4ml).This mixture is stirred 5 minutes and adds alkali potassium tert.-butoxide (2.00mmol).By this solution stirring 12 hours.Measure productive rate by using dodecane (1.00mmol) as interior target GC.The results are summarized in Table IV.
Table IV:
Embodiment The catalyzer of following embodiment Start from the productive rate (%) of chlorobenzene Start from the productive rate (%) of bromobenzene
29 1 3 -
30 1 - 77
31 2 6 -
32 2 - 77
33 3 3 -
34 3 - 84
35 4 49 -
36 4 - 79
37 5 5 -
38 5 - 80
39 6 45 -
40 6 - 79
41 7 62 -
42 7 - 81
43 8 16 -
44 ｜8 - 68
45 9 64 -
46 9 - 83
47 10 - 43
48 11 - 59
49 12 - 53
50 13 - 83
51 14 4 -
52 14 - 83
III.2 the universal program of Sonogashira reaction
Under nitrogen atmosphere, the catalyzer of embodiment 15 (2mol%) is suspended in ethanol (1.00ml).Add bromobenzene (1.00mmol, 102 μ l) and 1-hexin (1.50mmol, 173 μ l).Finally add KOtBu (1mmol is dissolved in 1.00ml ethanol) and this mixture is stirred 12 hours at ambient temperature.Solvent for use is not for there is no in advance degassed technical grade ethanol.Add after this ammonium chloride (saturated solution, 2.00ml), ethyl acetate (4.00ml) and dodecane (1.00mmol, 226.2 μ l).By organic layer Na 2sO 4drying is also analyzed by GC.The productive rate of own-1-alkynyl benzene: 55%.
NHC-(transition metal) title complex of IV synthesis type I-E
The acyclic gold complex of IV.1 synthesis type (VI)
Approach a)
R 1, R 2, R 3, R 8, R 10and R 11there is above-mentioned implication.
In in typical program, 1-2 equivalent amine (6) being added to the solution of isocyanide fund (I) title complex (7) in methylene dichloride.This mixture is at room temperature stirred to 1-3 days.Under reduced pressure except desolventizing.Necessary, crude product is purified by the column chromatography (methylene dichloride is as eluent) on silica gel.
Approach b)
The synthetic of acyclic gold (I) Cabbeen (8) also can be started to realize with single still program by (tetramethylene sulfide) AuCl in methylene dichloride ((tht) AuCl).Adding R 1after-NC, this mixture is at room temperature stirred and within 1 hour, also adds subsequently amine (6).
All title complexs are air and hydrostabile and can at room temperature store and not decompose.
Embodiment 53: chloro ([amino { [2, the 6-diisopropyl phenyl] amino } methylene radical of cyclo-dodecyl (2,2-dimethoxy-ethyl)) aurate
Figure BDA00003115671900782
Title compound is used the 100mg (238mmol) 2 in the 5ml methylene dichloride according to universal program, 6-diisopropyl phenyl isocyano-gold trichloride (I) and the preparation of 71.2mg (250mmol) N-(2,2-dimethoxy-ethyl) cyclododecane amine.Reaction mixture is at room temperature stirred 24 hours and purifies by column chromatography, obtain the colourless crystallization solid; Output: 151mg (219mmol, 92%); 1h-NMR (300MHz, CD 2cl 2): δ=1.18 (d, J=6.9Hz, 6H, CH 3), 1.24-1.61 (m, 19H), 1.35 (d, J=6.9Hz, 6H, CH 3), 3.08 (sept, J=6.9Hz, 2H, CH), 3.47 (s, 6H, OCH 3), 3.56 (d, J=4.8Hz, 2H, CH 2n), 4.51 (t, J=4.8Hz, 1H, CH (OCH 3) 2), 7.21 (d, J=7.4Hz, 2H, ArH), 7.50 (t, J=7.4Hz, 1H, ArH); 13c-NMR (75MHz, CD 2cl 2): δ=22.55 (t, 2C), 22.68 (t, 2C), (23.29 q, 2C), 23.59 (q, 2C), (24.14 t, 2C), 24.62 (t, 2C), (24.67 t, 1C), 28.68 (d, 2C), (29.51 t, 1C), 48.75 (t, 2C), (53.83 q, 2C), 64.83 (d, 1C), (105.01 d, 1C), 124.14 (d, 2H), 129.47 (d, 1C), (135.89 s, 1C), 146.99 (s, 2C), 198.34 (s, 1C); IR (KBr): ν=3540,3268,2931,2864,1592,1537,1469,1445,1414,1384,1362,1331,1240,1197,1162,1119,1056,1016,801,759cm -1; HR-MS (FAB +): m/z=690.3202, C 29h 50auClN 2o 2calculated value [M] +: 690.3226, m/z=655.3509.C 29h 50auN 2o 2calculated value [M-Cl -] +: 655.3538.
IV.2 synthesizes acyclic (palladium or platinum) title complex
Figure BDA00003115671900791
M is Pd or Pt;
R 1, R 2, R 3, R 8, R 10and R 11as defined above.
In exemplary program, under room temperature and nitrogen atmosphere by cis-(isonitrile) 2-MeCl 2title complex (9) and 1 equivalent amine (6) stir 2-5 days in anhydrous THF.The completely consumed of raw material is by the skew monitoring of the IR stretching frequency of this isonitrile part.Under reduced pressure, except desolventizing, crude product is dissolved in minimum methylene dichloride and with ether layer and covers, this brings out this acyclic arbine complex (10) as the clear crystal crystallization.Crystal is leached, with Skellysolve A or ether washing drying under reduced pressure.These title complexs are air and hydrostabile and can at room temperature store and not decompose.
Embodiment 54
Figure BDA00003115671900801
Title compound is used at the 70mg of the anhydrous THF of 8ml (0.31mmol) cis-[PdCl according to above-mentioned exemplary program 2(2,6-diisopropyl phenyl isonitrile) 2and 58.1mg (0.31mmol) N-(2,2-dimethoxy-ethyl) hexahydroaniline preparation.Output: 204mg (276mmol, 89%); 1h-NMR (500MHz, CD 2cl 2): δ=0.93 (d, J=6.9Hz, 3H, CH 3), 1.08 (d, J=6.9Hz, 3H, CH 3), 1.13 (d, J=6.9Hz, 3H, CH 3), 1.23 (d, J=6.9Hz, 6H, CH 3), 1.24 (d, J=6.9Hz, 6H, CH 3), 1.52 (d, J=6.9Hz, 3H, CH 3), 1.52-1.72 (m, 6H), 1.82 (m, 1H), 1.96 (m, 3H), 2.45 (m, 1H), 2.87 (sept, J=6.9Hz, 1H, CH), 3.06 (sept, J=6.9Hz, 2H, CH), 3.51 (s, 3H, CH 3), 3.60 (s, 3H, CH 3), 3.71 (d, J=4.7Hz, 2H, CH 2), 3.88 (sept, J=6.9Hz, 1H, CH), 4.57 (t, J=4.7Hz, 1H, CH), 7.11 (m, 1H, ArH), 7.23 (m, 2H, ArH), 7.44 (m, 3H, ArH), 8.71 (bs, 1H, NH); 13c-NMR (500MHz, CD 2cl 2):; 20.88,22.56,22.97 (2C), 23.35 (2C), 25.63,25.70,25.88 (2C), 26.04 (2C), 26.0828.84,29.72,29.98 (2C), 31.36,31.60,50.17,55.34,57.01,68.37,105.59,123.05,124.1,125.1,129.77,131.18,134.65,145.85,146.15 (2C), 149.38,191.16; IR (KBr): ν=3447,3262,2964,2932,2863,2185,1665,1630,1591,1543,1463,1418,1386,1360,1331,1142,1119,1060,800,750cm -1; HR-MS (FAB +): m/z=702.3038, C 36h 55clN 3o 2calculated value [the M-Cl of Pd -] +: 702.3028, m/z=667.3921, C 36h 55n 3o 2calculated value [the M-2Cl of Pd -] +: 667.3329.
The title complex of IV.3 synthesis type I-E
In typical program, respectively by acyclic Au (I)-title complex (8) and Pd (II)-or Pt (II) title complex (10) be dissolved in methylene dichloride.Add HCl (4N HCl) and this mixture is at room temperature stirred 12 hours.Under reduced pressure except desolventizing.Necessary words are purified crude product by the column chromatography (methylene dichloride is as eluent) on silica gel, the quantitative yield of usining obtains this NHC title complex as crystalline solid.All title complexs are air and hydrostabile and can at room temperature store and not decompose.
Embodiment 55: chloro 1-encircles octyl group-3-[2,6-di-isopropyl) and phenyl]-1,3-dihydro-2H-imidazoles-2-subunit } aurate
Figure BDA00003115671900811
By 100mg (0.16mmol) chloro in the 5ml methylene dichloride ([amino { [2, the 6-diisopropyl phenyl] amino } methylene radical of ring octyl group (2,2-dimethoxy-ethyl)) aurate and 0.25ml HCl, (4N, two in alkane) at room temperature stir 12 hours.Evaporating solvent obtains title compound with the colourless crystallization solid; Output: 90.0mg (0.16mmol,>99%); 1h NMR (300MHz, CD 2cl 2): δ=1.12 (d, J=6.9Hz, 6H), 1.28 (d, J=6.9Hz, 6H), 1.38-1.96 (m, 10H), 2.02-2.18 (m, 4H), (2.33 sept, J=6.9Hz, 2H), 5.01 (quin, J=6.9Hz, 1H), 6.95 (d, J=1.9Hz, 1H), 7.24 (d, J=1.9Hz, 1H), 7.31 (d, J=7.8Hz, 2H), 7.49 (t, J=7.8Hz, 1H); 13c NMR (75MHz, CD 2cl 2): δ=24.54 (q, 2C), 24.62 (q, 2C), 24.91 (t, 2C), 26.35 (t, 1C), 27.22 (t, 2C), (28.97 d, 2C), 34.78 (t, 2C), 62.72 (d, 1C), 118.27 (d, 1C), 123.94 (d, 1C), (124.66 d, 2C), 130.91 (d, 1C), 146.48 (s, 2C), 147.07 (s, 1C), 172 (s, 1C); IR (KBr): ν=3433,2961,2925,1865,1544,1471,1459,1423,1411,1385,1364,1307,1254,1194,1120,1058,873,807,765,740; HR-MS (FAB +): m/z=570.2086, C 23h 34auClN 2calculated value [M] +: 570.2076.
The synthetic formula I-F compound that wherein M is Au-Cl of IV.4
Figure BDA00003115671900812
R 1, R 2, R 4, R 7, R 8with EWG above having to one of implication.
Method A: should be dissolved in anhydrous DCM and add this amine (1.50 equivalent) by [AuCl (isonitrile)] (1.00 equivalent) title complex under nitrogen atmosphere.This mixture is stirred 48 hours and removal of solvent under reduced pressure.The gained solid by petroleum ether to remove residual amine.Perhaps, crude product can pass through the column chromatography purification of the mixture of use silicon-dioxide and petrol ether/ethyl acetate (5:1).
Method B: should [AuCl (tht)] (1.00 equivalent) (tht=tetramethylene sulfide) be dissolved in anhydrous DCM and add this isonitrile (1.00 equivalent) under nitrogen atmosphere.This mixture is at room temperature stirred 5 minutes and add this amine (1.50 equivalent).This mixture is at room temperature stirred 48 hours and removal of solvent under reduced pressure.The gained solid by petroleum ether to remove residual amine.Perhaps, crude product can pass through the column chromatography purification of the mixture of use silicon-dioxide and petrol ether/ethyl acetate (5:1).
Embodiment 56:(1-cyclo-dodecyl-3-(2,6-diisopropyl phenyl)-4-(2-methoxyl group-2-oxoethyl)-imidazolidine-2-subunit) gold trichloride (I)
Figure BDA00003115671900821
Colorless solid, 80.0mg, 114 μ mol, 38%;
1h NMR (301MHz, CD 2cl 2) δ=1.17 (d, J=6.8Hz, 3H ,-CH 3), 1.19 (d, J=6.8Hz, 3H ,-CH 3), 1.21 (d, J=6.8Hz, 3H ,-CH 3), 1.30 (d, J=6.8Hz, 3H ,-CH 3), 1.14-1.84 (m, 22H ,-CH 2-), 2.67 (m, J=6.8Hz, 1H ,-CH-), 2.92 (m, J=6.8Hz, 1H ,-CH 3), 3.32 (dd, J=11.5,10.5Hz, 1H ,-CH 2-), 3.48 (s, 3H ,-OCH 3), 3.99 (d, J=11.2Hz, 1H ,-CH 2-), 4.27 (m, 1H ,-CH-), 4.63 (m, 1H ,-CH-), 7.15 (m, 2H, ArH), 7.34 (t, J=7.7Hz, 1H, ArH); 13c NMR (75MHz, CD 2cl 2) δ=22.49 (t), 22.59 (t), 22.95 (t), 23.24 (t), 23.34 (t), 23.46 (q), 24.10 (q), 24.24 (t), 24.41 (t), 24.66 (t), 24.95 (t), 25.47 (q), 26.30 (q), 28.62 (t), 28.84 (d), 29.15 (d), 29.25 (t), 37.93 (t), 50.54 (t), 52.36 (q), 55.92 (d), 61.41 (d), 124.99 (d), 125.36 (d), 130.30 (d), 133.20 (s), 147.83 (s), 148.34 (s), 170.55 (s), 194.45 (s, the Cabbeen carbon atom).
Embodiment 57:(1-cyclo-dodecyl-4-(2-methoxyl group-2-oxoethyl)-3-(2-(trifluoromethyl) phenyl) imidazolidine-2-subunit) gold trichloride (I)
Figure BDA00003115671900831
Colorless solid, 115mg, 167 μ mol, 56%; 1h NMR (300MHz, CD 2cl 2) δ=1.06-1.83 (m, 22H ,-CH 2-), 2.50 (m, 2H ,-CH 2-), 3.49 (m, 1H ,-CH 2-), 3.52 (s, 3H ,-CH 3), 3.90 (t, J=11.0Hz, 1H ,-CH 2-), 4.55 (m, 1H ,-CH-), 4.64 (m, 1H ,-CH-), 7.41 (d, J=7.7Hz, 1H, ArH), 7.54 (m, 1H, ArH), 7.63 (t, J=7.7Hz, 1H, ArH), 7.72 (d, J=7.7Hz, 1H, ArH); IR (KBr) ν=2935,2862,1738,1605,1585,1500,1459,1438,1316,1266,1207,1174,1130,1062,1037,999,773,645,599
Embodiment 58:(1-cyclo-dodecyl-4-(2-methoxyl group-2-oxoethyl)-3-(naphthalene-2-yl) imidazolidine-2-subunit) gold trichloride (I)
Figure BDA00003115671900832
Colorless solid, 149mg, 223 μ mol, 74%; 1h NMR (300MHz, CD 2cl 2) δ=1.10-1.87 (m, 22H ,-CH 2-), 2.45 (dd, J=16.5,9.0Hz, 1H ,-CH 2-), 2.64 (dd, J=16.5,4.3Hz, 1H ,-CH 2-), 3.48 (m, 1H ,-CH 2-), 3.50 (s, 3H ,-CH 3), 3.97 (t, J=11.3Hz, 1H ,-CH 2-), 4.71 (m, 1H ,-CH-), 4.83 (m, 1H ,-CH-), 7.46 (m, 2H, ArH), 7.56 (m, 1H, ArH), 7.82 (m, 4H, ArH).

Claims (26)

1. a method for preparing the compound of general formula (I):
Figure FDA00003115671800011
Wherein
N is 0 or 1,
The group that M is the containing metal atom,
R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R 2be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R wherein 1and R 2mean hydrogen when different,
R 3and R 4independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Perhaps R 3and R 4with together with the carbon atom of their institute's bondings, be C=O,
Perhaps R 3for group O-R 3aand
For n=0, R 4and R 7mean to be equal to respectively with R 4and R 7carbon atom between the key of two keys,
Perhaps
For n=1, R 4and R 5mean to be equal to respectively with R 4and R 5carbon atom between the key of two keys, wherein
R 3afor the group via carbon atom, Siliciumatom, sulphur atom, phosphorus atom, boron atom or titanium atom and oxygen bonding,
R 5, R 6, R 7and R 8independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Two radicals R wherein 2and R 8can also and R 2the N atom of institute's bonding forms together can optionally have 1,2 or 3 independently selected from O, N, NR awith other heteroatomss of S or containing heteroatom group the 3-12 person's nitrogen heterocyclic that does not replace or replace as ring members, wherein R afor hydrogen, alkyl, cycloalkyl or aryl,
Perhaps
If n=0, R 4and R 7can also mean to be equal to R 4and R 7carbon atom between the key of two keys,
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With general formula (III) or compound (IIIa), react:
Figure FDA00003115671800021
Figure FDA00003115671800022
Wherein
N, R 2, R 3, R 4, R 5, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y is leavings group, or
If R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, Y is group O-Y a, Y wherein afor the alkyl that does not replace or replace, the aryl that does not replace or replace, the aryl carbonyl that does not replace or replace or the alkyl-carbonyl that does not replace or replace, and
B1) optionally, if R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, make at step a1) in the product that obtains and compound R that wherein Z is leavings group 3a-Z is further reaction under alkali exists, and obtains wherein R 3for group O-R 3aand for n=0, R 4and R 7mean to be equal to and R 4and R 7the key of the two keys between the carbon atom of bonding or for n=1, R 4and R 5mean to be equal to and R 4and R 5the formula of the key of the two keys between the carbon atom of bonding (I) compound,
Perhaps
A2) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With the compound of logical formula V, react:
Figure FDA00003115671800031
Wherein
R 2, R 3and R 8above having to one of implication; And
R 10and R 11independently selected from C 1-C 4alkyl or R 10and R 11be can be by one or more C together 1-C 4the linear C that alkyl replaces 2-C 4alkylidene group;
Obtain the midbody compound of formula (VI):
Figure FDA00003115671800032
R wherein 1, R 2, R 3, R 8, R 10, R 11with M as defined above,
And
B2), with the midbody compound of acid treatment formula (VI), wherein in compound (I), n is 0 and R 4and R 7mean to be equal to R 4and R 7carbon atom between the key of two keys;
Perhaps
A3) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With general formula (IIIb) or compound (IIIc), react:
Figure FDA00003115671800041
Wherein
R 2, R 4, R 7and R 8above having to one of implication;
X -for the negatively charged ion Equivalent; And
EWG is (C (O) R 14, C (O) OR 14, NO 2, S (O) R 14or S (O) 2r 14, R wherein 14for hydrogen, alkyl, cycloalkyl or aryl;
Wherein according to scheme a3) in the compound (I) that obtains, n is 0 and R 3for CH 2-EWG.
2. according to the process of claim 1 wherein
N is 0 or 1,
The group that M is the containing metal atom,
R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R 2be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R wherein 1and R 2mean hydrogen when different,
R 3and R 4independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Perhaps R 3and R 4with together with the carbon atom of their institute's bondings, be C=O,
Perhaps R 3for group O-R 3aand for n=0, R 4and R 7mean to be equal to respectively with R 4and R 7carbon atom between the key of two keys,
Perhaps for n=1, R 4and R 5mean to be equal to respectively with R 4and R 5carbon atom between the key of two keys, wherein
R 3afor the group via carbon atom, Siliciumatom, sulphur atom, phosphorus atom, boron atom or titanium atom and oxygen bonding,
R 5, R 6, R 7and R 8independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Two radicals R wherein 2and R 8can also and R 2the N atom of institute's bonding forms together can optionally have 1,2 or 3 independently selected from O, N, NR awith other heteroatomss of S or containing heteroatom group the 3-12 person's nitrogen heterocyclic that does not replace or replace as ring members, wherein R afor hydrogen, alkyl, cycloalkyl or aryl,
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M(II)
R wherein 1with M above having to one of implication,
With general formula (III) or compound (IIIa), react:
Figure FDA00003115671800052
Wherein
N, R 2, R 3, R 4, R 5, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y is leavings group, or
If R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, Y is group O-Y a, Y wherein afor the alkyl that does not replace or replace, the aryl that does not replace or replace, the aryl carbonyl that does not replace or replace or the alkyl-carbonyl that does not replace or replace, and
B1) optionally, if R 3and R 4with together with the carbon atom of their institute's bondings, be C=O, make at step a1) in the product that obtains and compound R that wherein Z is leavings group 3a-Z is further reaction under alkali exists, and obtains wherein R 3for group O-R 3aand for n=0, R 4and R 7mean to be equal to and R 4and R 7the key of the two keys between the carbon atom of bonding or for n=1, R 4and R 5mean to be equal to and R 4and R 5the formula of the key of the two keys between the carbon atom of bonding (I) compound.
3. according to the method for claim 1 or 2, R wherein 1and R 2there are different implications.
4. according to the method for claim 1 or 2, wherein M is the group containing Pd (II), Pt (II) or Au (I).
5. according to the method for claim 4, wherein M is selected from PdCl 2(CNR 1), PtCl 2(CNR 1), Au (CNR 1) and AuCl, wherein R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl.
6. according to the method for any one in aforementioned claim, R wherein 1be selected from the group of formula IV.1-IV.5:
Figure FDA00003115671800061
Wherein
# means the bonding position with nitrogen-atoms,
P is 0 or 1,
X is 2 or 3, wherein when x is 2, with radicals R icarbon atom additionally with 1 hydrogen atom,
X in formula IV.2, IV.3 and IV.4 1be 0,1,2 or 3,
X in formula IV.2, IV.3 and IV.4 2be 0 or 1,
Condition is x in formula IV.2, IV.3 and IV.4 1and x 2summation be 0,1,2 or 3,
X in formula IV.5 1be 0,1 or 2,
X in formula IV.5 2be 0 or 1,
Condition is x in formula IV.5 1and x 2summation be 0,1 or 2,
A when existing, be can by one or more being selected from-O-and-C at the non-adjacent group interval of S- 1-C 10alkylidene group,
Radicals R ibe selected from independently of one another C 1-C 30alkyl, C 1-C 30alkoxyl group or C 1-C 30alkylthio, wherein the alkyl chain in alkyl, alkoxyl group or alkylthio can be by one or more non-adjacent Sauerstoffatom intervals.
7. according to the method for any one in aforementioned claim, R wherein 2be selected from alkyl and cycloalkyl, be preferably selected from methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, cyclo-dodecyl and 1-adamantyl.
8. according to the method for any one in claim 1-7, it is for the preparation of general formula (I-A.1) or compound (I-A.2):
Wherein
M, R 1, R 2, R 5, R 6, R 7and R 8there is implication as defined as any one in claim 1-7, R 3and R 4independently selected from hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M(II)
R wherein 1there is one of above-mentioned implication with M,
With general formula (III) or compound (IIIa), react:
Wherein
N, R 2, R 3, R 4, R 5, R 6, R 7and R 8there is one of above-mentioned implication,
X -for the negatively charged ion Equivalent, and
Y is leavings group.
9. method according to Claim 8, it is for the preparation of the compound of general formula (I-A.2.1):
Figure FDA00003115671800082
Wherein M, R 1, R 2, R 3and R 7there is implication as defined as any one in claim 1-7.
10. according to Claim 8 or 9 method, wherein R 3, R 4, R 7, R 8and if the words R existed 5and R 6be all hydrogen.
11., according to the method for any one in claim 1-7, it is for the preparation of general formula (I-B.1) or compound (I-B.2):
Figure FDA00003115671800083
Wherein M, R 1, R 2, R 5, R 6, R 7and R 8there is implication as defined as any one in claim 1-7,
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M(II)
R wherein 1with M above having to one of implication,
With general formula (III-B.1), (III-B.1.a), (III-B.2) or compound (III-B.2.a), react:
Figure FDA00003115671800091
Wherein
R 2, R 5, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y afor the alkyl that does not replace or replace, the aryl that does not replace or replace or the alkyl-carbonyl that does not replace or replace.
12., according to the method for claim 11, it is for the preparation of the compound of general formula (I-B.2.1):
Figure FDA00003115671800092
Wherein M, R 1and R 2there is implication as defined as any one in claim 1-7.
13., according to the method for any one in claim 1-7, it is for the preparation of general formula (I-C.1) or compound (I-C.2):
Figure FDA00003115671800093
Wherein M, R 1, R 2, R 3a, R 6, R 7and R 8there is implication as defined as any one in claim 1-7,
The method comprises:
A1) make the isocyanide complex of general formula (II):
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With general formula (III-C.1), (III-C.1.a), (III-C.2) or compound (III-C.2.a), react:
Wherein
R 2, R 6, R 7and R 8above having to one of implication,
X -for the negatively charged ion Equivalent, and
Y afor the alkyl that does not replace or replace, the aryl that does not replace or replace or the alkyl-carbonyl that does not replace or replace, and
B1) make at step a1) in the product that obtains and compound R that wherein Z is leavings group 3a-Z is further reaction under alkali exists.
14., according to the method for claim 13, it is for the preparation of the compound of general formula (I-C.2.1):
Figure FDA00003115671800102
Wherein
M, R 1, R 2and R 3athere is implication as defined as any one in claim 1-7.
15. according to the method for claim 13 or 14, wherein R 3abe selected from the group of formula V-A, V-B, V-C, V-D, V-E, V-F, V-G, V-H, V-I, V-K or V-L:
Figure FDA00003115671800103
Wherein
# means the bonding position with Sauerstoffatom,
Be selected from-O-of T and-NR vf, R wherein vffor hydrogen, alkyl, cycloalkyl or aryl,
R va, R vband R vhbe selected from the alkyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vc, R vd, R vebe selected from independently of each other the alkyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vgbe selected from the Heterocyclylalkyl that does not replace or replace,
R viand R vkbe selected from independently of each other the alkyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace, alkoxyl group, the aryloxy that does not replace or replace and the cycloalkyloxy that does not replace or replace,
R vmand R vnbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R voand R vpbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vq, R vrand R vsbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vt, R vuand R vvbe selected from independently of each other the alkyl that does not replace or replace, the alkenyl that does not replace or replace, the cycloalkyl that does not replace or replace, the aryl that does not replace or replace and the heteroaryl that does not replace or replace,
R vw, R vxand R vybe selected from independently of each other the alkoxyl group that does not replace or replace, the alkenyloxy that does not replace or replace, the cycloalkyloxy that does not replace or replace and the aryloxy that does not replace or replace; And D +for the positively charged ion Equivalent.
16. according to the method for any one in aforementioned claim, wherein at step a1) in reaction at alkali, under the alkali that is preferably selected from tertiary amine exists, carry out.
17. according to the method for any one in aforementioned claim, wherein at step b1) in reaction at alkali, under preferred non-nucleophilicity alkali, especially two (trimethyl silyl) Lithamide exist, carry out.
18., according to the method for any one in claim 1-7, it is for the preparation of the compound of general formula (I-E):
Figure FDA00003115671800121
Wherein M, R 1, R 2, R 3and R 8there is implication as defined as any one in claim 1-7,
The method comprises:
A2) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with M above having to one of implication,
With the compound of logical formula V, react:
Figure FDA00003115671800122
Wherein
R 2, R 3and R 8above having to one of implication; And
R 10and R 11independently selected from C 1-C 4alkyl or R 10and R 11be can be by one or more C together 1-C 4the linear C that alkyl replaces 2-C 4alkylidene group;
Obtain the midbody compound of formula (VI):
Figure FDA00003115671800123
R wherein 1, R 2, R 3, R 8, R 10, R 11with M as defined above;
And
B2) use the midbody compound of acid treatment formula (VI).
19., according to the method for any one in claim 1-7, it is for the preparation of the compound of general formula (I-F):
Figure FDA00003115671800131
R wherein 1, R 2, R 4, R 7, R 8, as above institute's implication of M and EWG,
The method comprises:
A3) make the isocyanide complex of general formula I I:
R 1-N≡C-M (II)
R wherein 1with as above institute's implication of M,
With general formula (IIIb) or compound (IIIc), react:
Figure FDA00003115671800132
Wherein
X -for the negatively charged ion Equivalent; And
R 2, R 4, R 7, R 8with EWG as defined above.
20., according to the method for claim 18 or 19, wherein M is AuCl.
21. the compound of a general formula as defined as any one in claim 1-15 and 18-20 (I).
22. a catalyzer, the compound that comprises general formula as defined as any one in claim 1-15 and 18-20 (I) or formed by it.
23. the compound of general formula as defined as any one in claim 1-15 and 18-20 (I) as C-C, C-O, C-N or c h bond form used catalyst in reaction purposes or as described in purposes in catalyzer.
24., according to the purposes of claim 23, it is for being selected from the C-C linked reaction of Suzuki reaction, Heck reaction, Sonogashira reaction, Stille reaction and Kumada reaction.
25., according to the purposes of claim 23, it is for being selected from the reaction of hydrogenation, hydroformylation, hydrosilylation, Hartwig-Buchwald reaction and acid amides alpha-aromatic.
26. the compound of a general formula (VI):
Wherein
R 1be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R 2be selected from hydrogen, alkyl, cycloalkyl, Heterocyclylalkyl, aryl and heteroaryl,
R wherein 1and R 2mean hydrogen when different,
R 3for hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
R 8for hydrogen and the alkyl that does not replace in each case or replace, alkoxyl group, alkylthio, (monoalkyl) amino, (dialkyl group) amino, cycloalkyl, cycloalkyloxy, cycloalkylthio, (monocycle alkyl) amino, (bicyclic alkyl) amino, Heterocyclylalkyl, heterocycle alkoxyl group, heterocycle alkylthio, (single Heterocyclylalkyl) amino, (two Heterocyclylalkyls) amino, aryl, aryloxy, arylthio, (single aryl) amino, (diaryl) amino, heteroaryl, heteroaryloxy, heteroarylthio, (single heteroaryl) amino and (two heteroaryls) amino
Two radicals R wherein 2and R 8can also and R 2the N atom of institute's bonding forms together can optionally have 1,2 or 3 independently selected from O, N, NR awith other heteroatomss of S or containing heteroatom group the 3-12 person's nitrogen heterocyclic that does not replace or replace as ring members, wherein R afor hydrogen, alkyl, cycloalkyl or aryl,
R 10and R 11independently selected from C 1-C 4alkyl or R 10and R 11be can be by one or more C together 1-C 4the linear C that alkyl replaces 2-C 4alkylidene group; And
The group that M is the containing metal atom.
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