CN1182113C - 2,5-cis-bisubstituted pyrrolidine derivative and its preparing process and usage - Google Patents

2,5-cis-bisubstituted pyrrolidine derivative and its preparing process and usage Download PDF

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CN1182113C
CN1182113C CNB021361290A CN02136129A CN1182113C CN 1182113 C CN1182113 C CN 1182113C CN B021361290 A CNB021361290 A CN B021361290A CN 02136129 A CN02136129 A CN 02136129A CN 1182113 C CN1182113 C CN 1182113C
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CN1390833A (en
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麻生明
焦宁
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The present invention relates to a 2, 5-cis-substituted pyrrolidine derivative, a multi-component one-reactor method for synthesizing the 2, 5-cis-substituted pyrrolidine derivative, and the purpose for synthesizing chiral adjuvant, or a ligand molecule dice, or a compound containing a bioactive pyrrolidine ring. The structural formula of the 2, 5-cis-substituted pyrrolidine derivative is disclosed in the formula, wherein R<1> is hydrogen or a C<1-10> alkyl group; R<2> is hydrogen or a C<1-10> alkyl group; R<3> is hydrogen, a C<1-8> alkyl group, or a benzyl group; R<4> is hydrogen or a C<1-10> alkyl group; R<5> is a phenyl group, a phenyl group of a paraposition substituted C<1-3> alkyl group, a phenyl group of a paraposition substituted OR<7> electron donating group, a phenyl group of paraposition substituted halogen, a phenyl group of a paraposition substituted COOR<8> electron withdrawing group, o-methylbenzyl, 2'-thienyl, (E)-styryl or (E)-CH2=CHR<9>; R<6> is hydrogen, a C<1-3> alkyl group, an electron donating group OR<10>, an electron withdrawing group COOR<11>, a nitro group or halogen; E is an electron withdrawing group COOR<12>, a nitrile group or a sulphone group SO2Ph; Ts is p-tosyl; R<7> is a C<1-4> alkyl group; R<8> is a C<1-10> alkyl group; R<9> is a C<1-8> alkyl group; R<10> is a C<1-4> alkyl group; R<11> is a C<1-10> alkyl group; R<12> is a C<1-10> alkyl group or a phenyl group.

Description

2,5-cis-disubstituted pyrroles alkane derivatives, preparation method and use
Technical field
The present invention relates to a class 2,5-cis-disubstituted pyrroles alkane derivatives, new synthetic method and uses thereof.This method is a catalyzer with Pd (O), catalysis Organohalogen compounds, 2-(2,3-joins thiazolinyl)-dimethyl malonate, and imine reaction, the high regioselectivity of one kettle way, highly-solid selectively Synthetic 2,5-cis-disubstituted pyrroles alkane derivatives.This compound is as a kind of important molecule stripping and slicing, itself may have certain physiologically active, also can be used for further synthesizing some and contain some compounds of pyrrolidine ring, these compounds that contain pyrrolidine ring all have very strong biological activity, such as to α, and β Glycosylase, α, enzymes such as β mannosidase, tilactase are inhibited, DNA there is strong affinity, can be used as microbiotic etc., also can utilize this quasi-molecule stripping and slicing further synthetic chirality assistant agent or parts.
Background technology
Since tetramethyleneimine molecular skeleton unit extensively be present in natural product, part, and some have in the biomacromolecule of physiologically active, therefore, this compounds has caused numerous scientists' great interest.Document D.Enders, C.Thiebes, Pure.Appl.Chem.2001,73,573; D.O hagan, Nat.Prod.Rep.2000,17,435; A.R.Pinder, Nat.Prod.Rep.1992,9,17; G.Massiot, C.Ddelaude, Inthe Alkaloids, A.Brossi, Ed., Academic Press:New York, 1996,27,269; To the existing elaborate report of the character of this type of pyrrolidin derivatives.Have α such as these compounds that contain pyrrolidine ring, β Glycosylase, α, enzyme inhibitions such as β mannosidase, tilactase have strong affinity to DNA, can be used as microbiotic etc., also can be used as some chirality assistant agent or parts.Therefore, paid attention to, and become the focus of organic synthesis research field by numerous organic chemist about the structure of pyrrolidine ring skeleton.Although document S.-K.Kang, K.-J.Kim, Org.Lett.2001,3,511; I.W.Davies, D.I.C.Scopes, T.Gallagher, Synlett 1993,85; I.W.Davies, T.Gallagher, R.B.Lamont, D.I.C.Scopes, J.Chem.Soc.Chem.Commun.1992,335; D.N.A.Fox, D.Lathbury, M.F.Mahon, K.C.Molloy, T.Gallagher, J.Chem.Soc.Chem.Commun.1989,1073; R.Kinsman, D.Lathbury, P.Vernon, T.Gallagher, J.Chem.Soc.Chem.Commun.1987,243; V.M.Arredondo, S.Tian, F.E.McDonald, T.J.Marks, J.Am.Chem.Soc.1999,121,3633; Reported that wherein several cyclizations of transition metal-catalyzed γ-Lian alkene acid amides that utilize generate the pyrrolidin derivatives that 2-replaces.But utilizing the transition metal-catalyzed connection alkene with functionalization is the multi-component reaction of starting raw material, and the method for the synthetic polysubstituted pyrrole alkane derivatives of one kettle way is not appeared in the newspapers.
Summary of the invention
The purpose of this invention is to provide a kind of new compound, promptly 2, the pyrrolidin derivatives that 5-cis-replaces.
Another purpose of the present invention provides a kind of new effective synthetic method of above-claimed cpd.Utilize this method can make 2 of the synthetic high regioselectivity of one pot of three component, highly-solid selectively, 5-cis-disubstituted pyrroles alkane derivatives, along reverse proportionality (cis/trans) can reach＞99: 1.Thereby make this compounds obtain more applications.
It is a kind of above-mentioned 2 that purpose of the present invention also provides, the purposes of the pyrrolidin derivatives that 5-cis-replaces.
Of the present invention 2, the pyrrolidin derivatives that 5-cis-replaces has following structural formula:
Figure C0213612900051
Wherein, R 1Can be hydrogen or C 1-10Alkyl; R 2Be hydrogen or C 1-10Alkyl; R 3Can be hydrogen, C 1-8Alkyl, benzyl; R 4Be hydrogen or C 1-10Alkyl; R 5For phenyl, by C 1-3The phenyl of alkyl para-orientation, by OR 7The phenyl of para-orientation, by the phenyl of halogen para-orientation, by COOR 8The phenyl of para-orientation, o-methyl-phenyl-, 2 '-thienyl, (E)-styryl, (E)-CH 2=CHR 9R 6Be hydrogen, C 1-3Alkyl, electron-donating group OR 10, electron withdrawing group COOR 11, nitro or halogen; E is drawing electron group COOR 12, itrile group or sulfuryl SO 2Ph; Ts is a p-toluenesulfonyl.
R 7Be C 1-4Alkyl, R 8Be C 1-10Alkyl, R 9Be C 1-8Alkyl, R 10Be C 1-4Alkyl, R 11Be C 1-10Alkyl, R 12Be C 1-10Alkyl or phenyl.
The invention provides 2 of the synthetic high regioselectivity of one pot of three component, highly-solid selectively, the novel method of 5-cis-disubstituted pyrroles alkane derivatives, in the product that obtains, the cis isomer to the ratio of trans isomer the highest can＞99: 1, reaction formula is as follows:
In the formula, R 1Can be hydrogen or C 1-10Alkyl; R 2Be hydrogen or C 1-10Alkyl; R 3Can be hydrogen, C 1-8Alkyl, benzyl; R 4Be hydrogen or C 1-10Alkyl; R 5Be phenyl, para-orientation C 1-3The phenyl of alkyl, para-orientation OR 7The phenyl of the phenyl of donor residues, para-orientation halogen, para-orientation COOR 8The phenyl of electron withdrawing group, o-methyl-phenyl-, 2 '-thienyl, (E)-styryl, (E)-CH 2=CHR 9R 6Be hydrogen, C 1-3Alkyl, electron-donating group OR 10, electron withdrawing group COOR 11, nitro or halogen; E is drawing electron group COOR 12, itrile group, sulfuryl SO 2Ph; Ts is a p-toluenesulfonyl.
R 7Be C 1-4Alkyl, R 8Be C 1-10Alkyl, R 9Be C 1-8Alkyl, R 10Be C 1-4Alkyl, R 11Be C 1-10Alkyl, R 12Be C 1-10Alkyl or phenyl.
Specifically in the presence of the organic solvent neutralization bases, the adding structural formula is method of the present invention
Figure C0213612900061
Connection ene compound, Organohalogen compounds R 5I and structural formula are
Figure C0213612900062
Group with imine moiety, under organic palladium (O) catalyst, react and obtain 2,5-cis-disubstituted pyrroles alkane derivatives.Temperature of reaction is 30～120 ℃; Reaction times is 3～60 hours; The mol ratio of connection ene compound, palladium catalyst, Organohalogen compounds, group with imine moiety and alkali is followed successively by 1: 0.01～0.3: 1～10: 1～10: 1～100.Adopt more alkali to not influence of reaction.
Wherein used organic palladium (O) catalyzer can be palladium/1,4-two (diphenylphosphino) butane, palladium/triphenylphosphine, palladium/1,2-two (diphenylphosphino) ethane, palladium/1,3-two (diphenylphosphino) propane, palladium/two chloro-(1,1 '-two (diphenylphosphino) ferrocene, tetra-triphenylphosphine palladium, Pd 2(dba) 3CHCl 3/ 1,4-two (diphenylphosphino) butane, Pd 2(dba) 3CHCl 3/ triphenylphosphine, Pd 2(dba) 3CHCl 3/ 1,2-two (diphenylphosphino) ethane, Pd 2(dba) 3CHCl 3/ 1,3-two (diphenylphosphino) propane, Pd 2(dba) 3CHCl 3/ two chloro-(1,1 '-two (diphenylphosphino) ferrocene, π-allyl palladium chloride/1,4-two (diphenylphosphino) butane, π-allyl palladium chloride/1,2-two (diphenylphosphino) ethane, π-allyl palladium chloride/triphenylphosphine, π-allyl palladium chloride/two chloro-(1,1 '-two (diphenylphosphino) ferrocene, π-allyl palladium chloride/1,3-two (diphenylphosphino) propane, dba is a diphenylacetylene ketone.
The alkali that reacts used can be the organic amine compound that contains lone-pair electron on the nitrogen-atoms, as benzyl lauryl amine, triethylamine, benzyl lauryl amine, Tributylamine, trioctylamine, diisopropyl ethyl amine, pyridine, bipyridine, 1,8-diazacyclo [4.3.0]-5-nonene, N, O-two-(trimethyl silicon based) ethanamide, 4-(N, the N-dimethyl)-and pyridine or 1,4-diazacyclo [2.2.2] octane etc.; Also can be monovalence metal inorganic alkali, as yellow soda ash, salt of wormwood, sodium hydride, cesium carbonate, Quilonum Retard, potassium hydroxide, sodium-acetate, Potassium ethanoate or sodium hydroxide etc.; Reaction solvent is conventional organic solvent such as normal hexane, hexanaphthene, toluene, tetrahydrofuran (THF), methylene dichloride, dimethyl formamide (DMF), 1,4-dioxane, acetone, ether.
The present invention is the preparation 2 of catalyst connection ene compound, Organohalogen compounds and group with imine moiety three component reaction highly-solid selectivelies first with organic palladium (O), 5-cis-disubstituted pyrroles alkane derivatives, simple to operate, be a kind of method easily and effectively.With existing Synthetic 2, the method for the pyrrolidines derivative that 5-cis-replaces is compared, and has overcome the drawback of traditional method, and have following characteristics: this is the catalytic multi-component reaction of one kettle way for (1), has kept Atom economy greatly.(2) one the step produced two chiral centres, and better controlled the reaction regioselectivity and stereoselectivity.(3) raw material conveniently is easy to get, and is simple to operate, convenient post-treatment.(4) conversion unit is simple, is easy to suitability for industrialized production.
Embodiment
Following examples help to understand the present invention, but are not limited to content of the present invention:
Embodiment 1
Cis-1-p-toluenesulfonyl-2-phenyl-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 78mg imines C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 61mg iodobenzene again.85 ℃ were reacted 6 hours, filtered, and (normal hexane: purifying ether=5: 1) obtains 111mg 1-p-toluenesulfonyl-2-phenyl-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine (cis/trans＞99: 1), productive rate 86% to column chromatography. 1H NMR (CDCl 3, 300MHz): δ=7.53 (d, J=8.29Hz, 2H), 7.30-7.41 (m, 5H), 7.11-7.28 (m, 7H), 5.86 (s, 1H), 5.36 (s, 1H), 5.25 (s, 1H), 4.50 (dd, J=11.68,5.98Hz, 1H), 3.65 (s, 3H), 3.15 (s, 3H), 2.84 (dd, J=13.70,11.68Hz, 1H), 2.60 (dd, J=13.70,5.98Hz, 1H), 2.39 (s, 3H); MS (70eV): m/z (%): 520 (14.32) [M ++ 1], 364 (100); IR (KBr): ν=1749,1729,1635,1597,1493,1350,1165cm -1Ultimate analysis: calculated value C 29H 29NO 6S (%): C 67.03, and H 5.63, and N 2.70; Observed value: C 67.04.H 5.48, N 2.63.
Embodiment 2
Cis-1-p-toluenesulfonyl-2-phenyl-3-itrile group-3-methyl-formiate base-5-(1 '-(4 '-propyl group phenyl)-2-propyl group pentenyl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 159mg yellow soda ash, 25mg Pd (PPh down 3) 4, 78mg imines C 6H 5=N-Ts adds 1, and 4-dioxane solvent 2mL adds 59mg 2-(4-propyl group-2 ', 3 '-pentadienyl) itrile group ethyl acetate and 92mg again to the propyl group iodobenzene.85 ℃ were reacted 15 hours; filter; (normal hexane: purifying ether=5: 1) obtains 124mg 1-p-toluenesulfonyl-2-phenyl-3-itrile group-3-methyl-formiate base-5-(1 '-(4 '-propyl group phenyl)-2-propyl group pentenyl) tetramethyleneimine (cis/trans＞95: 5), productive rate 81% to column chromatography. 1HNMR (CDCl 3, 300MHz): δ=7.23-7.75 (m, 13H), 5.40 (s, 1H), 4.39 (dd, J=11.83,5.70Hz, 1H), 3.67 (s, 3H), 2.48-2.76 (m, 4H), 2.36 (s, 3H), 2.26 (t, J=6.97Hz, 4H), 1.56-1.70 (m, 2H), 1.28-1.51 (m, 4H), 0.86-0.99 (m, 9H); MS (70eV): m/z (%): 612 (6.54) [M +], 91 (100); IR (KBr): ν=2262,1773,1742,1640,1355,1168cm -1Ultimate analysis: calculated value C 37H 44N 2O 4S (%): C 72.52, and H 7.24, and N 4.57; Observed value: C 72.63, H7.53, N 4.38.
Embodiment 3
Cis-1-p-toluenesulfonyl-2-phenyl-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-(4 "-the vinyl toluene base) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 194mg imines C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 66mg again to the methyl iodobenzene.85 ℃ were reacted 12 hours; filter, (normal hexane: purifying ether=5: 1) obtains 122mg 1-p-toluenesulfonyl-2-phenyl-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-(4 '-vinyl toluene base) tetramethyleneimine (cis/trans＞99: 1), productive rate 92%. 1H NMR (CDCl 3, 300MHz): δ=7.46 (d, J=8.40Hz, 2H), 7.25 (d, J=8.40Hz, 2H), 7.04-7.22 (m, 9H), 5.79 (s, 1H), 5.24 (s, 1H), 5.14 (s, 1H), 4.41 (dd, J=11.53,5.86Hz, 1H), 3.57 (s, 3H), 3.07 (s, 3H), 2.76 (dd, J=13.67,11.53Hz, 1H), 2.52 (dd, J=13.67,5.86Hz, 1H), 2.32 (s, 3H), 2.31 (s, 3H); MS (70eV): m/z (%): 533 (7.55) [M +], 416 (100); IR (KBr): ν=1771,1746,1646,1597,1511,1350,1162cm -1Ultimate analysis: calculated value C 30H 31NO 6S (%): C 67.52, and H 5.86, and N 2.62; Observed value: C 67.36, H 5.83, N 2.49.
Embodiment 4
Cis-1-p-toluenesulfonyl-2-phenyl-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-(2 "-the vinyl toluene base) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 106mg yellow soda ash, 15mg Pd (PPh down 3) 4, 194mg imines C 6H 5=N-Ts adds acetonitrile solvent 2mL, adds the adjacent methyl iodobenzene of 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 66mg again.85 ℃ were reacted 40 hours; filter, (normal hexane: purifying ether=5: 1) obtains 76mg 1-p-toluenesulfonyl-2-phenyl-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-(2 '-vinyl toluene base) tetramethyleneimine (cis/trans＞99: 1), productive rate 57%. 1H NMR (CDCl 3, 300MHz): δ=7.62 (d, J=8.06Hz, 2H), 7.40 (d, J=8.06Hz, 2H), 7.08-7.26 (m, 9H), 5.81 (s, 1H), 5.51 (s, 1H), 5.08 (s, 1H), 4.37 (dd, J=12.65,5.94Hz, 1H), 3.59 (s, 3H), 3.14 (s, 3H), 2.78 (t, J=12.65Hz, 1H), 2.55 (dd, J=12.65,5.94Hz, 1H), 2.40 (s, 3H), 2.38 (s, 3H); MS (70eV): m/z (%): 533 (1.57) [M +], 417 (100); IR (KBr): ν=1748,1730,1597,1491,1349,1165cm -1Ultimate analysis: calculated value C 30H 31NO 6S (%): C 67.52, and H 5.86, and N 2.62; Observed value: C 67.55, H 6.01, N 2.48.
Embodiment 5
Cis-1-p-toluenesulfonyl-2-(4-ethylphenyl)-3,3-dioctyl phthalate ethoxycarbonyl-4-methyl-5-methyl-5-(1 '-(4 '-ethoxyl phenenyl) octenyl) tetramethyleneimine:
Get a reaction tubes, nitrogen protection adds 203mg N, O-two-(trimethyl silicon based) ethanamide, 29mgPd (PPh down 3) 4, 287mg imines p-Et-C 6H 5=N-Ts adds N, and dinethylformamide solvent 2mL adds 81mg 1-methyl-2-methyl-2-(2 ', 3 '-decadiene thiazolinyl) diethyl malonate and 124mg again to the oxyethyl group iodobenzene.110 ℃ were reacted 7 hours; filter; column chromatography (normal hexane: purifying ether=5: 1); obtain 115mg 1-p-toluenesulfonyl-2-(4-ethylphenyl)-3; 3-dioctyl phthalate ethoxycarbonyl-4-methyl-5-methyl-5-(1 '-(4 '-ethoxyl phenenyl) octenyl) tetramethyleneimine (cis/trans＞97: 3), productive rate 63%. 1H NMR (CDCl 3, 300MHz): δ=6.91-7.52 (m, 12H), 5.82 (s, 1H), 5.54 (t, J=6.40Hz, 1H), 4.09 (q, J=7.15Hz, 4H), 3.96 (q, J=7.23Hz, 2H), 3.12 (q, J=6.42Hz, 1H), 2.44 (q, J=7.05Hz, 2H), 2.42 (s, 3H), 2.22-2.41 (m, 2H), 1.56 (s, 3H), 1.33 (t, J=7.23Hz, 3H), 1.10-1.29 (m, 17H), 1.06 (t, J=7.05Hz, 3H), 0.87 (t, J=7.53Hz, 3H); MS (70eV): m/z (%): 731 (8.42) [M +], 416 (100); IR (KBr): ν=1743,1720,1647,1358,1158cm -1Ultimate analysis: calculated value C 43H 57NO 7S (%): C 70.56, and H 7.85, and N 1.91; Observed value: C 70.35, H 7.99, N 1.80.
Embodiment 6
Cis-1-p-toluenesulfonyl-2-phenyl-3, (1 '-(4 '-methoxyl-styrene) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down to 3-dioctyl phthalate methoxycarbonyl-5- 3) 4, 78mg imines C 6H 5=N-Ts adds 1, and 4-dioxane solvent 2mL adds 46mg 2-(2,3-joins thiazolinyl) dimethyl malonate and 71mg again to the methoxyl group iodobenzene.85 ℃ were reacted 7 hours; filter, (normal hexane: purifying ether=5: 1) obtains 127mg 1-p-toluenesulfonyl-2-phenyl-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-(4 '-methoxyl-styrene) tetramethyleneimine (cis/trans＞98: 2), productive rate 90%. 1H NMR (CDCl 3, 300MHz): δ=7.53 (d, J=8.40Hz, 2H), 7.37 (d, J=8.40Hz, 2H), 7.09-7.17 (m, 7H), 6.90 (d, J=8.80Hz, 2H), 5.84 (s, 1H), 5.29 (s, 1H), 5.20 (s, 1H), 4.44 (dd, J=11.73,5.75Hz, 1H), 3.85 (s, 3H), 3.64 (s, 3H), 3.14 (s, 3H), 2.82 (dd, J=13.63,11.73Hz, 1H), 2.57 (dd, J=13.63,5.75Hz, 1H), 2.39 (s, 3H); MS (70eV): m/z (%): 549 (4.51) [M +], 416 (100); IR (KBr): ν=1745,1722,1647,1607,1511,1352,1246,1164cm -1Ultimate analysis: calculated value C 30H 31NO 7S (%): C 65.56, and H 5.68, and N 2.55; Observed value: C 65.51, H5.79, N 2.42.
Embodiment 7
Cis-1-p-toluenesulfonyl-2-phenyl-3, (1 '-(4 '-methyl-formiate base styryl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down to 3-dioctyl phthalate methoxycarbonyl-5- 3) 4, 194mg imines C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 79mg 4-Iodobenzoic acid methyl esters again.80 ℃ were reacted 9 hours; filter, (normal hexane: purifying ether=5: 1) obtains 133mg 1-p-toluenesulfonyl-2-phenyl-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-(4 '-methyl-formiate base styryl) tetramethyleneimine (cis/trans＞99: 1), productive rate 92%. 1H NMR (CDCl 3, 300MHz): δ=8.05 (d, J=8.51Hz, 2H), 7.43-7.58 (m, 4H), 7.12-7.33 (m, 7H), 5.85 (s, 1H), 5.46 (s, 1H), 5.34 (s, 1H), 4.49 (dd, J=11.58,5.94Hz, 1H), 3.96 (s, 3H), 3.65 (s, 3H), 3.14 (s, 3H), 2.80 (dd, J=13.71,11.58Hz, 1H), 2.58 (dd, J=13.71,5.94Hz, 1H), 2.40 (s, 3H); MS (70eV): m/z (%): 577 (5.03) [M +], 422 (100); IR (KBr): ν=1741,1721,1608,1435,1356,1280,1167cm -1Ultimate analysis: calculated value C 31H 31NO 8S (%): C 64.46, and H 5.41, and N 2.42; Observed value: C 64.36, H 5.38, N 2.25.
Embodiment 8
Cis-1-p-toluenesulfonyl-2-(4-ethoxyl phenenyl)-3,3-dioctyl phthalate carbobenzoxy-4-hexyl-5-benzyl-5-(1 '-(4 "-butyl formate base phenyl) the hexamethylene methylene radical) tetramethyleneimine:
Get a reaction tubes, nitrogen protection adds 20mg sodium hydroxide, 36mg Pd (PPh down 3) 4, 379mg imines p-EtO-C 6H 5=N-Ts adds toluene solvant 2mL, adds 138mg 1-hexyl-2-benzyl-2-(3-cyclohexylmethylene-2-propenyl) diphenyl malonate and 152mg 4-Iodobenzoic acid butyl ester again.100 ℃ were reacted 9 hours; filter; column chromatography (normal hexane: purifying ether=5: 1); obtain 203mg 1-p-toluenesulfonyl-2-(4 '-ethoxyl phenenyl)-3; 3-dioctyl phthalate carbobenzoxy-4-hexyl-5-benzyl-5-(1 '-(4 '-butyl formate base phenyl) hexamethylene methylene radical) tetramethyleneimine (cis/trans＞99: 1), productive rate 79%. 1H NMR (CDCl 3, 300MHz): δ=8.11 (d, J=8.46Hz, 2H), 7.70 (d, J=8.46Hz, 2H), 7.10-7.62 (m, 23H), 5.81 (s, 1H), 4.20 (t, J=7.25Hz, 2H), 3.96 (q, J=7.08Hz, 2H), 3.24-3.31 (m, 2H), 3.07 (d, J=14.15Hz, 1H), 2.40 (s, 3H), 1.88-2.14 (m, 4H), and 1.12-1.74 (m, 23H), 0.80-0.96 (m, 6H); MS (70eV): m/z (%): 1029 (3.12) [M +], 91 (100); IR (KBr): ν=1740,1718,1632,1353,1164cm -1Ultimate analysis: calculated value C 64H 71NO 9S (%): C 74.61, and H 6.95, N1.36; Observed value: C 74.89, H 7.18, N 1.24.
Embodiment 9
Cis-1-p-toluenesulfonyl-2-phenyl-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-(2 '-thienyl) vinyl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 194mg imines C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 63mg 2-iodothiophen again.85 ℃ were reacted 7 hours; filter, (normal hexane: purifying ether=5: 1) obtains 126mg 1-p-toluenesulfonyl-2-phenyl-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-(2 '-thienyl) vinyl) tetramethyleneimine (cis/trans＞99: 1), productive rate 100%. 1H NMR (CDCl 3, 300MHz): δ=7.53 (d, J=7.60Hz, 2H), 7.21-7.32 (m, 6H), 7.19 (d, J=7.60Hz, 2H), 7.09-7.16 (m, 1H), 6.98-7.06 (m, 1H), 5.83 (s, 1H), 5.48 (s, 1H), 5.37 (s, 1H), 4.51 (dd, J=11.23,6.23Hz, 1H), 3.65 (s, 3H), 3.14 (s, 3H), 2.89 (dd, J=13.85,11.23Hz, 1H), 2.78 (dd, J=13.85,6.23Hz, 1H), 2.39 (s, 3H); MS (70eV): m/z (%): 492 (2.36), 91 (100); IR (KBr): ν=1747,1729,1627,1596,1438,1351,1165cm -1Ultimate analysis: calculated value C 27H 27NO 6S 2(%): C 61.70, and H 5.18, and N 2.66; Observed value: C 61.47, H 5.15, N 2.62.
Embodiment 10
Cis-1-p-toluenesulfonyl-2-phenyl-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-methylene radical-3-phenyl-2 ' (E)-propenyl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 194mg imines C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 46 mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate again, and 69mg (E)-1-iodo-2-vinylbenzene.85 ℃ were reacted 7 hours; filter, (normal hexane: purifying ether=5: 1) obtains 130mg 1-p-toluenesulfonyl-2-phenyl-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-methylene radical-3 '-phenyl-2 ' (E)-propenyl) tetramethyleneimine (cis/trans=97: 3), productive rate 96%. 1H NMR (CDCl 3, 300MHz): δ=7.02-7.61 (m, 14H), 6.76 (d, J=16.15Hz, 1H), 6.64 (d, J=16.15Hz, 1H), 5.92 (s, 1H), 5.39 (s, 1H), 5.28 (s, 1H), 4.36 (dd, J=12.94,5.88Hz, 1H), 3.73 (s, 3H), 3.19 (s, 3H), 2.95 (t, J=12.94Hz, 1H), 2.68 (dd, J=12.94,5.88Hz, 1H), 2.31 (s, 3H); MS (70eV): m/z (%): 482 (2.51), 417 (100); IR (KBr): ν=1740,1598,1496,1456,1435,1347,1162cm -1Ultimate analysis: calculated value C 31H 31NO 6S (%): C68.24, H 5.73, and N 2.57; Observed value: C 68.11, N 5.94, N 2.38.
Embodiment 11
Cis-1-p-toluenesulfonyl-2-phenyl-3, and 3-dioctyl phthalate methoxycarbonyl-5-(1 '-methylene radical-2 '-(E)-heptenyl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 78mg imines C 6H 5=N-Ts adds 1, and 4-dioxane solvent 2mL adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate again, and 63mg (E)-1-iodo-1-hexene.85 ℃ were reacted 6.5 hours; filter, (normal hexane: purifying ether=5: 1) obtains 110mg 1-p-toluenesulfonyl-2-phenyl-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-methylene radical-2 '-(E)-heptenyl) tetramethyleneimine (cis/trans=97: 3), productive rate 84%. 1H NMR (CDCl 3, 300MHz): δ=7.50 (d, J=8.50Hz, 2H), 7.22-7.41 (m, 5H), 7.18 (d, J=8.50Hz, 2H), 6.10 (d, J=16.05Hz, 1H), 5.83 (s, 1H), 5.77 (dt, J=16.05,6.83Hz, 1H), 5.13 (s, 1H), 5.09 (s, 1H), 4.19 (dd, J=11.98,5.95Hz, 1H), 3.67 (s, 3 H), 3.18 (s, 3H), 2.85 (dd, J=13.88,11.98Hz, 1H), 2.59 (dd, J=13.88,5.95Hz, 1H), 2.38 (s, 3H), and 2.03-2.16 (m, 2H), 1.31-1.43 (m, 4H), 0.93 (t, J=7.15Hz, 3H); MS (70eV): m/z (%): 525 (0.53) [M +], 370 (100); IR (KBr): ν=1742,1649,1599,1435,1356,1268,1165cm -1Ultimate analysis: calculated value C 29H 35NO 6S (%): C 66.26, and H 6.71, and N 2.66; Observed value: C 66.23, H 6.60, N 2.61.
Embodiment 12
Cis-1-p-toluenesulfonyl-2-(4 '-butyl formate base phenyl)-3, the own ester group of 3-dioctyl phthalate-4-propyl group-5-(1 '-methylene radical-2 '-(E)-the decene base) tetramethyleneimine:
Get a reaction tubes, nitrogen protection adds 117mg pyridine, 3mg palladium, 10mg 1,2-two (diphenylphosphino) ethane, 270mg imines p-C down 4H 9OOCC 6H 5=N-Ts adds cyclohexane solvent 2mL, adds 92mg 1-propyl group-2-(2 ', 3 ' connection thiazolinyl) propanedioic acid dihexyl again, and 76mg (E)-1-iodo-1-nonene.80 ℃ were reacted 35 hours; filter; column chromatography (normal hexane: purifying ether=5: 1); obtain 136mg 1-p-toluenesulfonyl-2-(4 '-butyl formate base phenyl)-3; the own ester group of 3-dioctyl phthalate-4-propyl group-5-(1 '-methylene radical-2 '-(E)-the decene base) tetramethyleneimine (cis/trans=96: 4), productive rate 64%. 1H NMR (CDCl 3, 300MHz): δ=8.03 (d, J=8.38Hz, 2H), 7.56-7.72 (m, 4H), 7.30 (d, J=7.46Hz, 2H), 5.92 (dt, J=16.10,6.87Hz, 1H), 5.68 (s, 1H), 5.63 (d, J=16.10Hz, 1H), 5.49 (s, 1H), 5.40 (s, 1H), 4.53 (d, J=7.82Hz, 1H), 4.20 (t, J=7.23Hz, 2H), 4.01 (t, J=7.08Hz, 4H), 2.48-2.61 (m, 1H), 2.43 (s, 3H), 1.98-2.12 (m, 2H), 1.05-1.63 (m, 34H), 0.71-0.97 (m, 15H); MS (70eV): m/z (%): 849 (0.88) [M +], 91 (100); IR (KBr): ν=1738,1645,1587,1350,1163cm -1Ultimate analysis: calculated value C 50H 75NO 8S (%): C 70.64, and H 8.89, N1.65; Observed value: C 70.38, H 8.97, N 1.50.
Embodiment 13
Cis-1-p-toluenesulfonyl-2-(4 '-nitrophenyl)-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 91mg imines p-NO 2-C 6H 5=N-Ts adds 1, and 4-dioxane solvent 2mL adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 61mg iodobenzene again.85 ℃ were reacted 6.5 hours; filter, (normal hexane: purifying ether=5: 1) obtains 134mg 1-p-toluenesulfonyl-2-(4-nitrophenyl)-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine (cis/trans=97: 3), productive rate 95%. 1H NMR (CDCl 3, 300MHz): δ=8.14 (d, J=8.54Hz, 2H), 7.78 (d, J=8.54Hz, 2H), 7.51-7.60 (m, 5H), 7.42 (d, J=8.64Hz, 2H), 7.32 (d, J=8.64Hz, 2H), 5.93 (s, 1H), 5.57 (s, 1H), 5.43 (s, 1H), 4.47 (dd, J=11.60,5.95Hz, 1H), 3.73 (s, 3H), 3.31 (s, 3H), 2.93 (dd, J=13.79,11.60Hz, 1H), 2.69 (dd, J=13.70,5.95Hz, 1H), 2.56 (s, 3H); MS (70eV): m/z (%): 461 (40.77), 91 (100); IR (KBr): ν=1755,1739,1641,1607,1599,1526,1356,1167cm -1Ultimate analysis: calculated value C 29H 28N 2O 8S (%): C 61.69, and H 5.00, and N 4.96; Observed value: C 61.57, H 5.03, N 4.77.
Embodiment 14
Cis-1-p-toluenesulfonyl-2-(4 '-hexyl formate base phenyl)-3,3-two benzenesulfonyls-5-hexyl-5-(1 '-(4 '-bromobenzene) vinyl) tetramethyleneimine:
Get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 13mg Pd down 2(dba) 3CHCl 3, 11mg 1,4-two (diphenylphosphino) butane, 388mg imines p-C 4H 9OOCC 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 108mg 3-(2 ', 2 '-two benzenesulfonyls) ethyl-1 again, and 2-nonadiene and 142mg are to bromo-iodobenzene.85 ℃ were reacted 16 hours; filter; column chromatography (normal hexane: purifying ether=5: 1); obtain 173mg 1-p-toluenesulfonyl-2-(4-hexyl formate base phenyl)-3; 3-two benzenesulfonyls-5-hexyl-5-(1 '-(4 '-bromobenzene) vinyl) tetramethyleneimine (cis/trans=95: 5), productive rate 71%. 1H NMR (CDCl 3, 300MHz): δ=8.57 (d, J=8.49Hz, 2H), 8.19 (d, J=8.49Hz, 2H), 7.64-8.10 (m, 16H), 7.27 (d, J=7.75Hz, 2H), 6.07 (s, 1H), 5.93 (s, 1H), 5.87 (s, 1H), 4.21 (t, J=6.88Hz, 2H), 2.91 (d, J=14.32Hz, 1H), 2.80 (d, J=14.32Hz, 1H), 2.42 (s, 3H), 1.72-1.88 (m, 1H), 1.54-1.68 (m, 1H), 1.12-1.48 (m, 16H), 0.87 (t, J=7.32Hz, 3H), 0.80 (t, J=7.28Hz, 3H); MS (70eV): m/z (%): 973 (2.32) [M +-1], 975 (2.38) [M ++ 1]; IR (KBr): ν=1745,1643,1359,1158cm -1Ultimate analysis: calculated value C 50H 56BrNO 8S 3(%): C 61.59, and H 5.79, and N 1.44; Observed value: C 61.37, H 5.92, N 1.20.
Embodiment 15
Cis-1-p-toluenesulfonyl-2-(4 '-p-methoxy-phenyl)-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 218mg imines p-MeO-C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 61mg iodobenzene again.85 ℃ were reacted 6 hours; filter, (normal hexane: purifying ether=5: 1) obtains 136mg 1-p-toluenesulfonyl-2-(4 '-p-methoxy-phenyl)-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine (cis/trans＞99: 1), productive rate 99%. 1H NMR (CDCl 3, 300MHz): δ=7.54 (d, J=8.23Hz, 2H), 7.32-7.46 (m, 5H), 7.20 (d, J=8.23Hz, 2H), 7.07 (d, J=6.75Hz, 2H), 6.73 (d, J=6.75Hz, 2H), 5.80 (s, 1H), 5.33 (s, 1H), 5.23 (s, 1H), 4.46 (dd, J=11.73,6.00Hz, 1H), 3.78 (s, 3H), 3.63 (s, 3H), 3.19 (s, 3H), 2.81 (dd, J=13.53,11.73Hz, 1H), 2.57 (dd, J=13.53,6.00Hz, 1H), 2.39 (s, 3H); MS (70eV): m/z (%): 549 (2.91) [M +], 91 (100); IR (KBr): ν=1739,1640,1612,1514,1355,1253,1165cm -1Ultimate analysis: calculated value C 30H 31NO 7S (%): C 65.56, and H 5.68, and N 2.55; Observed value: C 65.64, H 5.83, N 2.52.
Embodiment 16
Cis-1-p-toluenesulfonyl-2-(4 '-bromophenyl)-3-benzenesulfonyl-3-group-4 ethyl formate-5-propyl group-5-(1 '-styryl) tetramethyleneimine: get a reaction tubes; nitrogen protection adds 12mg sodium hydride (60%), 5mg π-allyl palladium chloride, 30mg two chloro-(1,1 '-two (diphenylphosphino) ferrocene, 254mg imines p-Br-C down 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 81mg 2-(2-propyl group 2 ', 3 '-Lian thiazolinyl)-2-benzenesulfonyl ethyl acetate and 61mg iodobenzene again.65 ℃ were reacted 18 hours; filter; (normal hexane: purifying ether=5: 1) obtains 140mg1-p-toluenesulfonyl-2-(4-' bromophenyl)-3-benzenesulfonyl-3-group-4 ethyl formate-5-propyl group-5-(1 '-styryl) tetramethyleneimine (cis/trans＞99: 1), productive rate 76% to column chromatography. 1H NMR (CDCl 3, 300MHz): δ=8.42 (d, J=8.55Hz, 2H), 7.13-7.92 (m, 16H), 5.71 (s, 1H), 5.55 (s, 1H), 5.21 (s, 1H), 4.20 (q, J=7.27Hz, 2H), 3.07 (d, J=15.85Hz, 1H), 2.94 (d, J=15.85Hz, 1H), 2.38 (s, 3H), 1.80-1.94 (m, 1H), and 1.61-1.74 (m, 1H), 1.26-1.34 (m, 2H), 1.21 (t, J=7.08Hz, 3H), 0.91 (t, J=6.88Hz, 3H); MS (70eV): m/z (%): 735 (4.68) [M +-1], 737 (4.56) [M ++ 1]; IR (KBr): ν=1749,1735,1640,1593,1345,1158cm -1Ultimate analysis: calculated value C 37H 38BrNO 6S 2(%): C 60.32, and H 5.20, and N 1.90; Observed value: C 60.11, H 5.45, N 1.81.
Embodiment 17
Cis-1-p-toluenesulfonyl-2-phenyl-3,3-dinitrile-5-(1 '-styryl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 326mg cesium carbonate, 13mg Pd down 2(dba) 3CHCl 3, 26mg triphenylphosphine, 130mg imines C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 30mg 2-(2 ', 3 '-Lian thiazolinyl) propane dinitrile and 61mg iodobenzene again.85 ℃ were reacted 8 hours, filtered, and (normal hexane: purifying ether=5: 1) obtains 91mg 1-p-toluenesulfonyl-2-phenyl-3,3-dinitrile-5-(1 '-styryl) tetramethyleneimine (cis/trans＞99: 1), productive rate 80% to column chromatography. 1H NMR (CDCl 3, 300MHz): δ=7.10-7.82 (m, 14H), 5.64 (s, 1H), 5.16 (s, 1H), 4.84 (s, 1H), 4.46 (dd, J=11.04,6.32Hz, 1H), 2.63 (dd, J=13.48,11.04Hz, 1H), 2.49 (dd, J=13.48,6.32Hz, 1H), 2.41 (s, 3H); MS (70eV): m/z (%): 453 (11.67) [M ++ 1], 91 (100); IR (KBr): ν=2258,1752,1733,1641,1354,1168cm -1Ultimate analysis: calculated value C 27H 23N 3O 2S (%): C 71.50, and H 5.11, N9.26; Observed value: C 71.29, H 5.33, N 9.18.
Embodiment 18
Cis-1-p-toluenesulfonyl-2-(4 '-chloro-phenyl-)-3,3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine: get a reaction tubes, nitrogen protection adds 138mg salt of wormwood, 15mg Pd (PPh down 3) 4, 89mg imines p-Cl-C 6H 5=N-Ts adds tetrahydrofuran solvent 2mL, adds 46mg 2-(2 ', 3 '-Lian thiazolinyl) dimethyl malonate and 61mg iodobenzene again.85 ℃ were reacted 7 hours; filter, (normal hexane: purifying ether=5: 1) obtains 132mg 1-p-toluenesulfonyl-2-(4 '-chloro-phenyl-)-3 to column chromatography; 3-dioctyl phthalate methoxycarbonyl-5-(1 '-styryl) tetramethyleneimine (cis/trans＞98: 2), productive rate 95%. 1H NMR (CDCl 3, 300MHz): δ=7.58 (d, J=8.15Hz, 2H), 7.32-7.48 (m, 5H), 7.24 (d, J=8.15Hz, 2H), 7.15 (d, J=8.30Hz, 2H), 7.01 (d, J=8.30Hz, 2H), 5.76 (s, 1H), 5.37 (s, 1H), 5.25 (s, 1H), 4.39 (dd, J=12.61,5.98Hz, 1H), 3.61 (s, 3H), 3.19 (s, 3H), 2.79 (t, J=12.61Hz, 1H), 2.56 (dd, J=12.61,5.98Hz, 1H), 2.42 (s, 3H); MS (70eV): m/z (%): 554 (2.08) [M +], 398 (100); IR (KBr): ν=1753,1731,1645,1597,1493,1348,1262,1162cm -1Ultimate analysis: calculated value C 29H 28NO 6S (%): C 62.87, and H 5.09, and N 2.53; Observed value: C 62.81, H 5.11, N2.46.

Claims (7)

1. a class 2, the pyrrolidin derivatives that 5-cis-replaces is characterized in that having following structural formula:
Figure C021361290002C1
Wherein, R 1Be hydrogen or C 1-10Alkyl; R 2Be hydrogen or C 1-10Alkyl; R 3Be hydrogen, C 1-8Alkyl or benzyl; R 4Be hydrogen or C 1-10Alkyl; R 5For phenyl, by C 1-3The phenyl of alkyl para-orientation, by OR 7The phenyl of para-orientation, by the phenyl of halogen para-orientation, by COOR 8The phenyl of para-orientation, o-methyl-phenyl-, 2 '-thienyl, (E)-styryl or (E)-CH 2=CHR 9R 6Be hydrogen, C 1-3Alkyl, electron-donating group OR 10, electron withdrawing group COOR 11, nitro or halogen; E is COOR 12, itrile group or sulfuryl SO 2Ph; Ts is a p-toluenesulfonyl; R 7Be C 1-4Alkyl, R 8Be C 1-10Alkyl, R 9Be C 1-8Alkyl, R 10Be C 1-4Alkyl, R 11Be C 1-10Alkyl, R 12Be C 1-10Alkyl or phenyl.
2. as claimed in claim 1 a kind of 2, the synthetic method of the pyrrolidin derivatives that 5-cis-replaces is characterized in that in the presence of the organic solvent neutralization bases, and the adding structural formula is Connection ene compound, Organohalogen compounds R 5I and structural formula are
Figure C021361290002C3
Group with imine moiety, reaction is 3～60 hours under 30～120 ℃ and organic palladium (0) catalyst, wherein, the mol ratio of connection ene compound, organic palladium (0) catalyzer, Organohalogen compounds, group with imine moiety and alkali is followed successively by 1: 0.01～0.3: 1～10: 1～10: 1～100, described alkali is the organic amine compound that contains lone-pair electron on monovalence metal inorganic alkali or the nitrogen-atoms, R 1-R 11According to claim 1, E according to claim 1.
3. as claimed in claim 2 a kind of 2, the synthetic method of the pyrrolidin derivatives that 5-cis-replaces, it is characterized in that described palladium (0) catalyzer is palladium/1,4-two (diphenylphosphino) butane, palladium/triphenylphosphine, palladium/1,2-two (diphenylphosphino) ethane, palladium/1,3-two (diphenylphosphino) propane, palladium/two chloro-(1,1 '-two (diphenylphosphino) ferrocene, tetra-triphenylphosphine palladium, Pd 2(dba) 3CHCl 3/ 1,4-two (diphenylphosphino) butane, Pd 2(dba) 3CHCl 3/ triphenylphosphine, Pd 2(dba) 3CHCl 3/ 1,2-two (diphenylphosphino) ethane, Pd 2(dba) 3CHCl 3/ 1,3-two (diphenylphosphino) propane, Pd 2(dba) 3CHCl 3/ two chloro-(1,1 '-two (diphenylphosphino) ferrocene, π-allyl palladium chloride/1,4-two (diphenylphosphino) butane π-allyl palladium chloride/1,2-two (diphenylphosphino) ethane, π-allyl palladium chloride/triphenylphosphine, π-allyl palladium chloride/two chloro-(1,1 '-two (diphenylphosphino) ferrocene or π-allyl palladium chloride/1,3-two (diphenylphosphino) propane, dba is a diphenylacetylene ketone.
4. a class 2 as claimed in claim 2, the eco-friendly synthetic method of the pyrrolidin derivatives that 5-cis-replaces, the organic amine compound that it is characterized in that containing on the described nitrogen-atoms lone-pair electron is triethylamine, diisopropyl ethyl amine, pyridine, dipyridyl, N, O-two-(trimethyl silicon based) ethanamide.
5. as claimed in claim 2 a kind of 2, the synthetic method of the pyrrolidin derivatives that 5-cis-replaces is characterized in that described monovalence metal inorganic alkali is yellow soda ash, salt of wormwood, sodium hydride, cesium carbonate, Quilonum Retard, potassium hydroxide, sodium-acetate, Potassium ethanoate or sodium hydroxide.
6. as claimed in claim 2 a kind of 2, the synthetic method of the pyrrolidin derivatives that 5-cis-replaces, it is characterized in that described organic solvent is normal hexane, hexanaphthene, toluene, tetrahydrofuran (THF), methylene dichloride, dimethyl formamide, 1,4-dioxane, acetone, ether.
7. a class 2 as claimed in claim 1, the purposes of the pyrrolidin derivatives that 5-cis-replaces, the compound that it is characterized in that being used for the molecule stripping and slicing of synthesis of chiral assistant agent or part or contain bioactive pyrrolidine ring.
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