CN109970713A - Amino acid chiral ligand, chiral catalyst and its corresponding preparation method and application containing double coordination group - Google Patents
Amino acid chiral ligand, chiral catalyst and its corresponding preparation method and application containing double coordination group Download PDFInfo
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- CN109970713A CN109970713A CN201910242142.1A CN201910242142A CN109970713A CN 109970713 A CN109970713 A CN 109970713A CN 201910242142 A CN201910242142 A CN 201910242142A CN 109970713 A CN109970713 A CN 109970713A
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- 239000003054 catalyst Substances 0.000 title claims abstract description 67
- 150000001413 amino acids Chemical class 0.000 title claims abstract description 50
- 239000003446 ligand Substances 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- 150000001875 compounds Chemical class 0.000 claims description 70
- 239000002904 solvent Substances 0.000 claims description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- 239000003513 alkali Substances 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 16
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 8
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 8
- 238000006555 catalytic reaction Methods 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 229910021640 Iridium dichloride Inorganic materials 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 150000008065 acid anhydrides Chemical class 0.000 claims description 4
- 150000001263 acyl chlorides Chemical class 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000013067 intermediate product Substances 0.000 claims description 3
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 3
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 239000007821 HATU Substances 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Chemical group O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 claims description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical class ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 claims description 2
- 229940113088 dimethylacetamide Drugs 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- -1 chloromethanes Alkane Chemical class 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 13
- 238000013461 design Methods 0.000 abstract description 8
- 125000003275 alpha amino acid group Chemical group 0.000 abstract description 7
- 238000011161 development Methods 0.000 abstract description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 44
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- 235000001014 amino acid Nutrition 0.000 description 35
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 238000004128 high performance liquid chromatography Methods 0.000 description 22
- 230000014759 maintenance of location Effects 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 15
- 239000007791 liquid phase Substances 0.000 description 15
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 230000006872 improvement Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000004913 activation Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- MILUBEOXRNEUHS-UHFFFAOYSA-N iridium(3+) Chemical compound [Ir+3] MILUBEOXRNEUHS-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- CYMRPDYINXWJFU-UHFFFAOYSA-N 2-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=CC=C1C(O)=O CYMRPDYINXWJFU-UHFFFAOYSA-N 0.000 description 1
- GGDYAKVUZMZKRV-UHFFFAOYSA-N 2-fluoroethanol Chemical compound OCCF GGDYAKVUZMZKRV-UHFFFAOYSA-N 0.000 description 1
- QGHDLJAZIIFENW-UHFFFAOYSA-N 4-[1,1,1,3,3,3-hexafluoro-2-(4-hydroxy-3-prop-2-enylphenyl)propan-2-yl]-2-prop-2-enylphenol Chemical group C1=C(CC=C)C(O)=CC=C1C(C(F)(F)F)(C(F)(F)F)C1=CC=C(O)C(CC=C)=C1 QGHDLJAZIIFENW-UHFFFAOYSA-N 0.000 description 1
- WREVVZMUNPAPOV-UHFFFAOYSA-N 8-aminoquinoline Chemical group C1=CN=C2C(N)=CC=CC2=C1 WREVVZMUNPAPOV-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Classifications
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2282—Unsaturated compounds used as ligands
- B01J31/2295—Cyclic compounds, e.g. cyclopentadienyls
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0033—Iridium compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0269—Complexes comprising ligands derived from the natural chiral pool or otherwise having a characteristic structure or geometry
- B01J2531/0275—Complexes comprising ligands derived from the natural chiral pool or otherwise having a characteristic structure or geometry derived from amino acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/827—Iridium
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to the amino acid chiral ligand containing double coordination group, chiral catalyst and its corresponding preparation method and application.Chiral ligand of the invention is prepared by amino acid cheap and easy to get, and the diversity of chiral ligand can be improved in the development of such chiral ligand.Such chiral ligand only needs single step reaction that can simply and efficiently prepare chiral Ir (III) catalyst.Chiral Ir (III) catalyst of the invention is the original coordination mode for introducing bidentate homing device in amino acid backbone and changing amino acid and Ir, enhances amino acid to Ir (III) catalyst chirality control ability.Design has synthesized such chirality Ir (III) catalyst for the first time, and the catalyst is applied successfully in the efficient asymmetric syntheses of chiral γ-cyclic lactam, and selectivity is up to 99%ee, illustrates that the catalyst has superior Stereo control ability.
Description
Technical field
The invention belongs to asymmetry catalysis to synthesize field, and in particular to the amino acid chiral containing double coordination group is matched
Body, chiral catalyst and its corresponding preparation method and application.
Background technique
The function dough of inertia c h bond is the research field that chemist is paid close attention to for a long time.C h bond function dough is will to divide
C h bond in son is directly translated into all kinds of functional groups, and for traditional synthesis chemistry, c h bond function dough has original
The advantages that material is easy to get, Atom economy is high, pollution is few.C h bond function dough reaction transition metal-catalyzed in recent years achieves
Development at full speed is efficiently constructed with having been realized in all kinds of chemical bonds.The critical issue of c h bond function dough reaction is to solve
The regioselectivity and stereoselectivity of c h bond, current most research work, which concentrates on, solves the problems, such as regioselectivity.And
Stereoselectivity c h bond function dough is reacted, especially asymmetry C (sp3)-H key function dough, it studies relatively fewer.
It traces it to its cause and mainly can be applied to C (sp at present3)-H key function dough chiral catalyst and chiral ligand type phase
It compares relatively limited.The reason of causing the situation may be various: first is that C (sp3) energy required for-H bond activation is opposite
Higher, reaction condition is harsher, and it is big to realize that transition state energy distinguishes difficulty；Second is that C (sp3)-H key itself stereo disparity very
It is small, to realize efficient stereoselectivity activation, it is necessary to which chiral catalyst or ligand have accurate Stereo control ability, increase
The design difficulty of chiral ligand or catalyst is added；Third is that it is incomplete to the research of reaction mechanism at present, it can not be new ligand
Design provides reference, further increases the design difficulty of chiral ligand or catalyst.
Iridium (III) catalyst is a kind of very important catalyst, is applied to in c h bond function dough research.
But iridium (III) catalyst type applicable at present is very rare, only diamine class, salicylimines, porphyrin, bidentate oxazoline/
The catalyst such as imidazoline and artificial enzyme can be applied to asymmetric C (sp3) reaction of-H key, and the research in the field is concentrated mainly on
C (the sp of activation3)-H key, such as: benzyl position, allylic, furans alpha-position isoreactivity site, and for inactive C (sp3)-H key
Research lack very much.Therefore, if can design a suitable for inactive asymmetry C (sp3) the reaction iridium (III) of-H key urges
Agent can not only enrich the type of chiral Ir (III) catalyst, but also such catalyst can be applied to all kinds of chiral molecules
In synthesis, there is very important scientific meaning.
Amino acid is chiral source the most abundant, can not only be used in principle directly as chiral ligand or catalyst, but also
It can be used as chiral precursor and synthesize other kinds of chiral ligand.It is considered that if amino acid backbone cheap and easy to get can be drawn
Enter into the design synthesis of novel Ir (III) catalyst, can effectively enrich the type of Ir (III) catalyst.Early in 1990
Amino acid is applied in the synthesis of Ir (III) complex by year Spain chemist Oro et al., the Ir more regrettably synthesized
(III) complex does not have any catalytic effect.So far, the case that amino acid is applied in the synthesis of Ir (III) catalyst is non-
It is often few, and Most amino-acids ligand can not efficiently control the central chirality of Ir (III), to can only obtain a pair of diastereomeric
Isomers, so that amino acid ligand can not be applied in the exploitation of efficient Ir (III) catalyst.Therefore, how ammonia is utilized
It is the current technical issues that need to address that base acid ligand, which synthesizes Ir (III) chiral catalyst with high-efficiency catalytic activity,.
Summary of the invention
The object of the present invention is to provide a kind of amino acid chiral ligand containing double coordination group, chirality Ir (III) catalysis
Agent and its corresponding preparation method and application.The present invention has synthesized the amino acid chiral ligand containing double coordination group first,
And the chiral ligand is applied in the exploitation of Ir (III) catalyst.In order to achieve the object of the present invention, the present invention is to amino acid
Skeleton is transformed, and bidentate group is introduced into amino acid backbone, changes amino acid ligand and is catalyzed chiral Ir (III)
Catalytic model in agent.It is confirmed by experimental result, the chiral ligand that the present invention designs can efficiently control Ir (III) catalysis
The central chirality of agent successfully prepares chiral Ir (III) catalyst with individual isomer.Such Ir (III) catalyst can be with
It is effectively applied to disactivation C (sp3)-H key function dough reaction in.
To achieve the above object, the present invention adopts the following technical scheme:
A kind of amino acid chiral ligand containing double coordination group, has the following structure general formula:
Wherein, the common structure of III compound of formulaIts α carbon atom is asymmetric carbon atom, is of the invention
Chiral ligand provides chiral space.Wherein, NR1R2Chiral space, R are formed with R3Coordination site is provided in conjunction with metal center.
Amino acid is used alone in the prior art as chiral ligand, the central chirality of Ir (III) can not be efficiently controlled.
The present invention in amino acid backbone by introducing double coordination group, and change amino acid matches bit model, to realize single structure
The synthesis of type chirality Ir (III) catalyst.
The specific preparation method of amino acid chiral ligand containing double coordination group of the invention is shown in embodiment.
Wherein, R is any one in methyl, ethyl, benzyl, phenyl, isopropyl, tert-butyl or tert-butyl deriveding group
Kind；
More there is preferred tert-butyl deriveding group specifically: by introducing aromatic ring group on tert-butyl, especially rich electricity
Sub- aromatic ring changes ligand electron density, increases the combination and recognition capability of catalyst and substrate, so that Stereo control be made more to increase
Effect.
NR1R2Any one in following group:
More preferably NR1R2Any one in following group:
R3Any one in following group；
R3Any one in more preferably following group:
As the further improvement of above-described embodiment, the amino acid chiral ligand containing double coordination group it is specific such as
Under:
Wherein AQ refers to 8- aminoquinoline group (i.e. C1 group), and NPhth is phthalic amide.
The present invention also provides a kind of amino acid chiral catalyst containing double coordination group, has the following structure logical
Formula:
R, R of IV compound of formula3、NR1R2With III compound R of formula, R3、NR1R2Correspondence is identical.Wherein, III chemical combination of formula
Object is the intermediate of IV compound of preparation formula, and includes III compound of formula in the skeleton structure of IV compound of formula.
The catalyst model of early period mainly utilizes two coordination sites of N, O of amino acid in conjunction with catalytic center Ir.It utilizes
Amino acid alpha-position substituent group, to control the chirality of Ir catalytic center, but the type catalyst is in and Ir phase due to R group
To reversed position, distance farther out, causes chiral control ability limited, Most amino-acids class ligand is unable to control Ir (III)
Central chirality, to can not be used as a kind of efficient catalyst.
Catalyst model of the invention is then to serve as chiral environment using amino acid, introduces and leads in amino acids
To group NR3, wherein R3In contain N coordinating group, NR3Two coordination sites of N, N are provided in conjunction with Ir catalytic center, due to R3In
N coordination site have strong σ-electron donation, the electron density and catalytic activity of Ir catalytic center can be enhanced.Aminoacid
NR in frame1R2The center Ir is acted on simultaneously with the chiral cavity of R composition, and relative distance is closer, in conjunction with closer, makes chiral control
Ability greatly enhances, so that Ir (III) catalyst be made to have more efficient chiral catalysis effect.Simultaneously because NR1R2With R's
There are many alternative type, can significantly improve the adjustability of ligand, to improve the diversity of Ir (III) catalyst.This hair
R, NR in bright designed chiral catalyst1R2And NR3Interaction makes such Ir (III) catalyst become a kind of efficient hand
Property catalyst.
As the further improvement of above-described embodiment, the R is more preferably one of following group:
The NR1R2One of more preferably following group:
The R3One of more preferably following group:
As the further improvement of above-described embodiment, a kind of amino acid chiral catalysis containing double coordination group
Agent specifically:
The preparation method of the present invention also provides a kind of amino acid chiral catalyst containing double coordination group is specific to wrap
Include following steps: III compound of formula, [Cp*IrCl2]2, alkali C be added in solvent E, it is anti-under room temperature~40 degree, stirring condition
It answers, column chromatography method obtains IV compound of formula；
It is further preferred that III compound of formula: [Cp*IrCl2]2: alkali C is 1:0.4~0.5:3~10 with molar ratio
Additional amount is added in solvent E；The alkali C is potassium carbonate, sodium carbonate, cesium carbonate or lithium carbonate；The solvent E is methylene chloride
Or chloroform；Concentration of III compound of formula in solvent E is 1~10mol/L.
The application of the present invention also provides a kind of amino acid chiral catalyst containing double coordination group, by IV chemical combination of formula
Object is used for the asymmetry catalysis of following reaction, specifically includes the following steps: formula IV compound: Formula V compound is with molar ratio for 1:
50~100 additional amount is added in solvent F, is reacted 1~24 hour under 0~40 degree, stirring condition, and VI chemical combination of formula is made
Object；The solvent F is the mixed solvent of one of hexafluoroisopropanol, trifluoroethanol, hexafluoroisopropanol or trifluoroethanol with water,
The molar ratio of the hexafluoroisopropanol or trifluoroethanol and water is 1:0~10；Concentration of the formula IV compound in solvent F is
0.1~1 mol/L.
The R5Selected from one of aryl, alkyl, alkenyl or alkynyl.
Reaction mechanism is as it appears from the above, formula IV catalyst and Formula V compound are coordinated to obtain Formula VII intermediate, and then generation divides
Carbon dioxide eliminating reacts to obtain Formula VIII intermediate in son, and Formula VIII intermediate occurs intramolecular c h bond and selectively inserts
To Formula IX intermediate, which occurs reduction and eliminates, and the regeneration of the synthesis and formula IV catalyst of realizing Formula IV compound follows
Ring.
Beneficial effect
Chiral ligand of the invention is prepared by amino acid cheap and easy to get, from a wealth of sources, is conducive to expand chiral Ir (III)
The diversity of catalyst.Such chiral ligand only needs single step reaction that can simply and efficiently prepare chiral Ir (III) catalyst.
Chiral Ir (III) catalyst of the invention is that bidentate is introduced in amino acid backbone based on the Reconstruc-tion policy to amino acid backbone
Homing device changes original coordination mode of amino acid and Ir, and enhancing amino acid is first to Ir (III) catalyst chirality control ability
Secondary design has synthesized such chirality Ir (III) catalyst.The catalyst is applied successfully to the efficient of chiral γ-cyclic lactam
In asymmetric syntheses, selectivity is up to 99%ee, illustrates that the catalyst has superior Stereo control ability.
Chiral Ir (III) catalyst of the invention is applied in the efficient asymmetric syntheses of chiral γ-cyclic lactam.γ-ring
Pentanamide γ-position substituent group can be the groups such as aryl, alkenyl, alkynyl and alkyl, have extensive substrate adaptability.
The chiral ligand optical purity that the present invention synthesizes is up to 99%ee, this is also to prepare such optically pure chemical combination for the first time
Object；And the method for preparing such compound in the prior art can not be used to synthesize such chiral ligand.
Chiral Ir (III) catalyst of the invention is applied to can be simultaneous in the efficient asymmetric syntheses of chiral γ-cyclic lactam
Hold air atmosphere, solvent can also allow for the presence of water, and the presence of water can promote reaction rate in largely reaction
With selectivity, the defect that existing most of organic synthesis can only carry out in organic phase is overcome, development green is conducive to
The chemical synthesis of environmental protection.
Specific embodiment
The invention will be further elucidated with reference to specific embodiments.
A kind of amino acid chiral ligand containing double coordination group of the invention, has the following structure general formula:
Wherein, R is any in methyl, ethyl, benzyl, phenyl, isopropyl or tert-butyl or tert-butyl deriveding group
It is a kind of；
NR1R2Any one in following group；
R3Any one in following group；
Wherein, corresponding to contain double coordination base when R is selected from methyl, ethyl, benzyl, phenyl, isopropyl or tert-butyl
The amino acid chiral ligand of group is used uniformly following steps preparation:
Step 1: type I compound and acid anhydrides are under a reaction condition or type I compound and acyl chlorides are anti-under b reaction condition
It answers, II compound of formula is made；It is directly used after being spin-dried for, without purifying.
Wherein, a reaction condition are as follows: after the amount of type I compound and acid anhydrides with molar ratio for 1:1~2 is added, 160
~180 degree, it is dry stir under the conditions of react；
The b reaction condition are as follows: type I compound: acyl chlorides: solvent is added with molar ratio for the amount of 1:1~2:2~10 in alkali A
After in A, reacted under 0~25 degree, stirring condition；The alkali A is triethylamine or DIPEA；The solvent A is methylene chloride, three
Chloromethanes or DMF；
Step 2: II compound of formula and R3NH2It is reacted under c reaction condition or under d reaction condition, III compound of formula is made；
It is diluted with water, separates organic phase, after cleaning organic phase, merge organic phase, after dry filter is spin-dried for, obtain formula after chromatographing via column
III compound, III compound of formula is via repeated recrystallize (methylene chloride/petroleum ether), the available hand for being greater than 99% ee value
Property ligand.
Wherein, the c reaction condition are as follows: in II compound of formula: condensing agent: alkali B:R3NH2It is 1:1~2:2 with molar ratio
The additional amount of~3:0.8~1.5 is added in solvent B, reacts under room temperature, stirring condition；II compound of formula is in solvent B
Concentration be 1~10mol/L；The solvent B is methylene chloride or DMAC N,N' dimethyl acetamide；The condensing agent be HBTU or
HATU；The alkali B is DIPEA or triethylamine；
Wherein, the d reaction condition are as follows: in II compound of formula: oxalyl chloride or thionyl chloride are 1:5~10 with molar ratio
Additional amount is added in solvent C, and DMF is added as catalyst, after reacting under room temperature, stirring condition, is spin-dried for, and is made intermediate and produces
Object；The solvent C is methylene chloride, and the additional amount of the DMF is 1~10 drop；Concentration of II compound of formula in solvent C
For 1~10mol/L；
Then again by intermediate product, R3NH2And triethylamine is added jointly in solvent D, is reacted under room temperature, stirring condition,
III compound of formula is made；The R3NH2: triethylamine: the molar ratio of II compound of formula is 0.8~1.5:3~5:1；The solvent D
For methylene chloride.
Wherein the specific preparation condition of each amino acid chiral ligand is as follows: where for the convenience of description, I chemical combination of formula
Object, II compound of formula are unified general formula, and difference is that the group selected is different, and corresponding group is as shown in the table.
It when R is the deriveding group of tert-butyl, synthesizes with the following method: by L4, the compound pair indicated with L15-L20
Aryl iodide (4~6 equivalent), palladium acetate (0.1~0.3 equivalent), the silver acetate (0.8~1.5 equivalent) answered are added in chlorobenzene, in argon
Under conditions of gas shielded, after reaction 24~48 hours, it is cooled to room temperature, is spin-dried for after solvent being chromatographed by column being matched accordingly
Body.
The preparation process of L15-L20 amino acid chiral ligand compound is as follows:
Wherein the corresponding detection data of L1-L21 is as follows:
Hz, 2H), 7.73 (dd, J=5.5,3.1Hz, 2H), 7.51-7.46 (m, 2H), 7.39 (dd, J=8.3,4.2Hz, 1H),
5.26 (q, J=7.3Hz, 1H), 1.97 (d, J=7.3Hz, 3H)13C NMR(101MHz,CDCl3)δ167.96,167.34,
148.44,138.62, 136.41,134.31,134.01,132.13,127.98,127.43,123.69,122.03,
The er value of 121.75,116.74,50.23,15.51.HPLC:L1 (99.8:0.2) is via liquid-phase chromatographic analysis, the chirality that uses
Column isAD-H column (n-hexane: isopropanol=70:30,1.0mL/min, T=30 DEG C, 254nm), retention time
For 12.65min, 14.20min.
7.59-7.49 (m, 2H), 7.46-7.37 (m, 1H), 7.36-7.13 (m, 5H), 5.49 (t, J=9.8Hz, 1H), 3.92-3.76
(m,2H).13C NMR(101MHz,CDCl3)δ167.98,166.50,148.38,138.54,136.81,136.33,134.28,
133.93,131.69, 129.11,128.80,127.91,127.38,127.06,123.64,122.10,121.72,
Via liquid-phase chromatographic analysis, the chiral column used is the er value of 116.82,56.31,34.84.HPLC:L2 (> 99.9:0.1)LuxTMCellulose-1 column (n-hexane: isopropanol=70:30,1.0 mL/min, T=30 DEG C, 254nm),
Retention time is 13.3min, 14.4min.
(m, 1H), 1.22 (d, J=6.6Hz, 3H), 0.99 (d, J=6.6Hz, 3H)13C NMR(101MHz,CDCl3)δ168.18,
166.89,148.59, 138.73,136.23,134.33,134.31,131.62,127.94,127.26,123.68,
122.05,121.69,117.00,63.25,27.38,20.53,19.66. the er value of HPLC:L3 (96:4) is via liquid chromatogram
Analysis, the chiral column used areLuxTMCellulose-1 column (n-hexane: isopropanol=70:30,1.0mL/
Min, T=30 DEG C, 254nm), retention time 8.70min, 10.26min.
2H), 4.45 (dd, J=8.0,3.2Hz, 1H), 3.76-3.62 (m, 1H), 3.43-3.32 (m, 1H), 2.38 (s, 3H), 3.32-
3.21(m,1H),1.96– 1.80(m,2H),1.78–1.66(m,1H).13C NMR(101MHz,CDCl3)δ169.98,
148.65,144.27,138.78,136.03,133.95, 133.45,129.85,127.99,127.84,126.93,
122.07,121.62,116.27,63.28,49.76,30.79,24.56,21.48.HRMS(ESI) m/z Calcd for
C21H22N3O3S+[M+H]+: the er value of 396.1376, found:396.1374.HPLC:L5 (> 99.9:0.1) is via liquid chromatogram
Analysis, the chiral column used areLuxTMCellulose-2 column (n-hexane: isopropanol=70:30,1.0mL/
Min, T=30 DEG C, 254nm), retention time 25.46min, 27.51min.
δ168.62,165.74,150.59,148.86,139.55,136.10,134.35,131.78,131.17,127.80,
125.76,123.75,120.72,120.47, 117.29,104.32,63.99,55.87,36.15,28.64.HRMS(ESI)
m/z Calcd for C24H24N3O4 +[M+H]+: the er value of 418.1761, found:418.1760.HPLC:L6 (99.4:0.6)
Via liquid-phase chromatographic analysis, the chiral column used isIC column (n-hexane: isopropanol=70:30,1.0mL/
Min, T=30 DEG C, 254nm), retention time 17.19min, 20.52min.
133.60,133.25,131.63,127.13,125.88,124.64,123.78,122.33,116.93,63.83,36.22,
28.53.HRMS(ESI)m/z Calcd for C23H21N3O3Cl+[M+H]+:422.1266,found:422.1268.HPLC:L7
Via liquid-phase chromatographic analysis, the chiral column used is the er value of (99:1)LuxTMCellulose-1 column (just oneself
Alkane: isopropanol=70:30,1.0mL/min, T=30 DEG C, 254nm), retention time 7.25min, 8.49min.
=9.0Hz, 1H), 1.19 (s, 9H)13C NMR(101MHz,CDCl3)δ169.34,167.38,148.56,138.53,
136.30,134.50,133.76,131.73,128.67,127.96,127.20,122.16,121.85,116.65,62.18,
35.86,26.94.HRMS(ESI) m/z Calcd for C22H24N3O2 +[M+H]+:362.1863,found:
362.1863.HPLC:L8 via liquid-phase chromatographic analysis, the chiral column used is the er value of (97.4:2.6)
LuxTMCellulose-1 column (n-hexane: isopropanol=70:30,1.0mL/min, T=30 DEG C, 254 nm), retention time is
4.70min,7.07min.
(d, J=9.4Hz, 1H), 5.13 (s, 2H), 4.35 (d, J=9.2Hz, 1H), 1.12 (s, 9H)13C NMR(101MHz,
CDCl3)δ169.39,156.51,148.54,138.58,136.34,133.85,128.63,128.22,128.00,127.32,
122.06,121.83,116.69, 103.25,67.16,64.26,35.29,26.78.HRMS(ESI)m/z Calcd for
C23H26N3O3 +[M+H]+: the er value of 392.1969, found:392.1966. HPLC:L9 (99.7:0.3) is via liquid chromatogram point
Analysis, the chiral column used areAY-H column (n-hexane: isopropanol=80:20,1.0mL/min, T=30 DEG C,
254nm), retention time 10.77min, 15.10min.
127.43,121.98,121.74,117.01,63.89,28.48.HRMS(ESI)m/z Calcd for C19H20N3O3 +[M+H+]: the er value of 338.1499, found:338.1497.HPLC:L11 (92:8) is via liquid-phase chromatographic analysis, the chirality that uses
Column isAY-H column (n-hexane: isopropanol=70:30,1.0mL/min, T=30 DEG C, 254nm), retention time
For 6.03min, 8.97min.
C23H18N3O3Br4 +[M+H]+: the er value of 703.8035, found:703.8026.HPLC:L12 (94.4:5.6) is via liquid phase color
Spectrum analysis, the chiral column used areAD-H column (n-hexane: isopropanol=70:30,1.0mL/min, T=30
DEG C, 254nm), retention time 12.23min, 17.96min.
121.74,121.49,116.98,63.85,36.31,28.56.HRMS(ESI)m/z Calcd for C27H24N3O3 +[M+H]+:
The er value of 438.1812, found:438.1813.HPLC:L13 (98.6:1.4) is via liquid-phase chromatographic analysis, the chirality that uses
Column isLuxTM1 column of Cellulose- (n-hexane: isopropanol=70:30,1.0mL/min, T=30 DEG C,
254nm), retention time 20.66min, 26.00min.
MHz,CDCl3)δ167.27,148.05,138.71,136.18,134.58,131.66,128.32,127.91,127.54,
127.18,121.39,121.24,116.77,62.10,36.63,29.09.HRMS(ESI)m/z Calcd for C27H24N3O3 +[M+H]+: the er value of 438.1812, found:438.1814.HPLC:L14 (99.4:0.6) is used via liquid-phase chromatographic analysis
Chiral column beAD-H column (n-hexane: isopropanol=70:30,1.0mL/min, T=30 DEG C, 254nm), protect
Staying the time is 7.49min, 12.45min.
131.68,130.03,127.92,127.33,123.74,121.84,121.56,117.02,113.29,62.83,55.21,
44.89,39.78,25.22,25.08. HRMS(ESI)m/z Calcd for C30H28N3O4 +[M+H]+:494.2074,
Via liquid-phase chromatographic analysis, the chiral column used is the er value of found:494.2070.HPLC:L15 (99.9:0.1)LuxTMCellulose-1 column (n-hexane: isopropanol=80:20,1.0mL/min, T=30 DEG C, 220nm),
Retention time is 11.2min, 17.5min.
158.07,148.23,138.67,136.26,134.42,134.17,132.37,131.90,131.70,130.39,129.91,
127.94,127.38,123.74, 121.91,121.61,116.91,113.66,113.25,59.35,55.25,55.18,
43.22,42.63,42.30,23.12.HRMS(ESI)m/z Calcd for C37H34N3O5 +[M+H]+:600.2493,found:
600.2493.HPLC:L16 via liquid-phase chromatographic analysis, the chiral column used is the er value of (99.9:0.1)
LuxTMCellulose-1 column (n-hexane: isopropanol=90:10,1.0mL/min, T=30 DEG C, 254nm), retention time is
22.03min,25.37min.
134.13,133.62,131.88,131.77,130.46,127.79,127.25,123.08,121.68,121.44,116.85,
113.48,57.87,55.05,55.02, 46.12,40.84.HRMS(ESI)m/z Calcd for C44H40N3O6 +[M+H]+:
The er value of 706.2912, found:706.2912.HPLC:L17 (> 99.9:0.1) is via liquid-phase chromatographic analysis, the chirality that uses
Column isLuxTMCellulose-1 column (n-hexane: isopropanol=80:20,1.0mL/min, T=30 DEG C,
220nm), retention time 15.78min, 18.55min.
128.24,127.89,127.30,123.83,122.08,121.61,116.89,58.72,52.04,51.97,43.60,
43.24, 43.21,23.12.HRMS(ESI)m/z Calcd for C39H34N3O7 +[M+H]+:656.2391,found:
656.2397.HPLC:L19 via liquid-phase chromatographic analysis, the chiral column used is the er value of (99.7:0.3)
LuxTMCellulose-4 column (n-hexane: isopropanol=70:30,1.0mL/min, T=30 DEG C, 254nm), retention time is
21.94min,29.97min.
(101MHz,CDCl3)δ168.50,166.66,160.59,160.29,148.30,140.69,140.30,138.71,
136.30,134.46,134.12, 131.80,127.99,127.42,123.83,121.99,121.67,117.00,
109.72,108.85,99.29,98.50,59.43,55.44,55.28,44.11, 43.76,43.24,23.86.HRMS
(ESI)m/z Calcd for C39H38N3O7 +[M+H]+:660.2704,found:660.2709.HPLC:L20 (99.8:0.2)
Er value via liquid-phase chromatographic analysis, the chiral column used isLuxTMCellulose-2 column (n-hexane: different
Propyl alcohol=70:30,1.0mL/min, T=30 DEG C, 254nm), retention time 12.9min, 24.3min.
The present invention also provides a kind of amino acid chiral catalyst containing double coordination group, has the following structure logical
Formula:
R, R of IV compound of formula3、NR1R2With III compound R of formula, R3、NR1R2Correspondence is identical.
Amino acid chiral catalyst containing double coordination group of the invention is used uniformly following steps preparation: specific packet
Include following steps: by III compound of formula, [Cp*IrCl2]2, alkali C be added in solvent E, it is anti-under room temperature~40 degree, stirring condition
It answers, column chromatography method obtains IV compound of formula；
As the further improvement of above-described embodiment, III compound of formula: [Cp*IrCl2]2: alkali C is with molar ratio for 1:
The additional amount of 0.4~0.5:3~10 is added in solvent E；The alkali C is potassium carbonate, sodium carbonate, cesium carbonate or lithium carbonate；Institute
Stating solvent E is dichloromethane or chloroform；Reaction density of III compound of formula in solvent E is 1~10mol/L.
Wherein, the detection data of chiral catalyst Ir-L1-Ir-L20 is as follows:
(d, J=6.8Hz, 6H), 1.54 (s, 15H), 1.50 (s, 30H)13C NMR(101MHz,CDCl3)δ177.70, 176.17,
168.67,167.96,151.06,150.22,149.54,149.10,145.70,145.63,138.21,137.95,133.60,
133.10,132.79, 132.28,129.86,129.71,128.95,128.88,122.94,122.62,121.97,
121.80,120.77,117.98,117.58,86.93,86.70,54.39, 52.64,19.47,17.74,8.56,
8.40.HRMS(ESI)m/z Calcd for C30H29IrN3O3 +[M-Cl-]+:672.1833,found:672.1832.
168.27,151.23,151.02,149.98,149.20,145.86,139.04,138.31,137.96,133.54,133.03,
132.05,130.34,130.00, 129.69,129.38,129.11,128.12,127.96,126.23,125.87,
122.95,122.83,122.22,121.70,120.32,118.07,117.51, 87.12,86.73,77.36,60.14,
56.69,37.36,36.86,8.74,8.56.HRMS(ESI)m/z Calcd for C36H33IrN3O3 +[M-Cl-]+:
748.2146,found:748.2147.
Hz, 0.6H), 1.54 (s, 6H), 1.53 (s, 9H), 1.15 (d, J=6.9 Hz, 2.4H), 1.05 (d, J=6.7 Hz, 2H),
0.92 (d, J=6.7 Hz, 1.2H)13C NMR(101 MHz,CDCl3)δ177.39,168.83,151.41,151.04,
149.50,148.68,145.69,137.89,137.70,133.12, 133.02,132.81,132.27,129.71,
129.11,129.06,128.77,122.73,122.68,122.18,121.86,121.82,120.02,117.18, 86.52,
59.61,31.09,21.58,19.41,19.26,8.81,8.69.HRMS(ESI)m/z Calcd for C32H33IrN3O3 +[M-
Cl-]+:700.2146, found:700.2149.
28.68,8.90.RMS(ESI)m/z Calcd for C33H35IrN3O3 +[M-Cl-]+:714.2302,found:714.2305.
2.37(m,3.2H),2.35–2.25(m,0.9H),2.15–2.02(m,1.4H),1.87–1.73(m,1.1H),1.71–1.62
(m,1H),1.59(s,5.2H), 1.53(s,10.7H).13C NMR(101 MHz,CDCl3)δ177.77,177.20,
151.37,150.97,149.56,149.38,146.40,142.77, 138.18,137.68,137.59,137.06,
129.60,129.54,129.45,129.42,128.89,128.86,128.14,127.80,123.81,122.44,
122.07,121.31,118.50,118.13,87.20,86.83,77.36,66.32,58.26,49.36,48.99,35.84,
31.89,29.80,24.80,24.25, 21.67,21.60,9.21,8.61.HRMS(ESI)m/z Calcd for
C31H35IrN3O3S+[M-Cl-]+:722.2023,found:722.2019.
HRMS(ESI)m/z Calcd for C34H37IrN3O4 +[M-Cl-]+:744.2408,found:744.2416.
60.64,38.50,28.66,8.90.HRMS(ESI)m/z Calcd for C33H34IrClN3O3 +[M-Cl-]+:748.1912,
found:748.1905.
131.16,129.92,129.13,128.98,128.95,128.69,128.58,127.41,127.02,122.65,122.52,
120.47,119.04,118.16, 87.10,86.51,62.45,39.53,36.97,29.81,27.96,26.77,9.05,
8.32.HRMS(ESI)m/z Calcd for C32H37IrN3O2 +[M- Cl-]+:688.2510,found:688.2512.
128.53,128.50,128.39,128.33,128.01,127.88,127.85,127.64,122.61,122.45,121.97,
120.16,119.73,118.87, 117.88,117.69,86.94,86.46,77.36,66.81,66.41,66.22,
63.14,38.82,27.64,27.54,26.58,8.99,8.26,8.19.HRMS (ESI)m/z Calcd for
C33H39IrN3O3 +[M-Cl-]+:718.2615,found:718.2615.
(ESI)m/z Calcd for C33H31Br4IrN3O3 +[M-Cl-]+:1029.8682,found:1029.8668.
129.88,129.71,129.57,129.21,127.94,123.51,122.23,121.64,116.71,86.46,60.88,
38.60,28.64,8.79.HRMS(ESI)m/z Calcd for C37H37IrN3O3 +[M-Cl-]+:764.2459,found:
764.2456.
C37H37IrN3O3 +[M-Cl-]+:764.2459,found:764.2458.
The application of the present invention also provides a kind of amino acid chiral catalyst containing double coordination group, in such catalysis
Under the action of agent, realize for C (sp3)-H key selective function with dough react, to be up to the stereoselectivity of 99%ee
Formula V compound is converted to Formula IV (γ-ring valeryl aminated compounds).
The R5Selected from one of aryl, alkyl, alkenyl or alkynyl.
Specifically includes the following steps: formula IV compound: Formula V compound is added with molar ratio for the additional amount of 1:50~100
It into solvent F, is reacted 1~24 hour under 10~40 degree, stirring condition, VI compound of formula is made；The solvent F is hexafluoro
The mixed solvent of one of isopropanol, trifluoroethanol, hexafluoroisopropanol or trifluoroethanol and water, the hexafluoroisopropanol or three
The molar ratio of fluoroethanol and water is 1:0~10；Concentration of the formula IV compound in solvent F is 0.1~1mol/L.
31.35,30.45.HPLC: via liquid-phase chromatographic analysis, the chiral column used is the er value of the productAY-H column
(n-hexane: isopropanol=70:30,1.0mL/min, T=30 DEG C, 220nm), retention time 4.04min, 6.91min, 99:
1er。
Phase chromatography tests the derivative of its Cbz, and the chiral column used is- IE column (n-hexane: isopropanol=
80:20,1.0 mL/min, T=30 DEG C, 220nm), retention time 16.91min, 19.19min, 99.3:0.7er.
1H), 1.62-1.43 (m, 2H), 0.94 (t, J=7.4 Hz, 3H)13C NMR(101 MHz,CDCl3)δ178.65,56.13,
30.43,29.63,26.89,10.13.HPLC: the er value of the product is surveyed using derivative of the liquid chromatogram to its Cbz
Examination, the chiral column used areAY-H column (n-hexane: isopropanol=90:10,1.0mL/min, T=30 DEG C,
220nm), retention time 19.06min, 23.76min, 99.3:0.7er.
CDCl3) δ 178.77,138.78,115.81,56.87,30.09,28.11.HPLC: the er value of the product is using liquid chromatogram
The derivative of its Cbz is tested, the chiral column used isIH column (n-hexane: isopropanol=80:20,
1.0mL/min T=30 DEG C, 220 nm), retention time 7.45min, 9.69min, 99:1er.
88.08,84.03,45.47,29.67,29.21.HPLC:The er value of 15 was determined by HPLC
analysis on aLuxTMCellulose-1 column (n-hexane: isopropanol=80:20,1.0mL/min, T=
30 DEG C, 220nm), retention time 7.0min, 9.3min, 99.5:0.5er.
In the description of the present invention, it should be noted that unless otherwise clearly defined and limited, term " installation ", " phase
Even ", " connection " shall be understood in a broad sense, for example, it may be being fixedly connected, may be a detachable connection, or be integrally connected；It can
To be mechanical connection, it is also possible to be electrically connected；It can be directly connected, can also can be indirectly connected through an intermediary
The connection of two components interiors.For the ordinary skill in the art, above-mentioned term can be understood by concrete condition
Concrete meaning in the present invention.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
1. a kind of amino acid chiral ligand containing double coordination group, characterized in that have the following structure general formula:
Wherein, any one of R in methyl, ethyl, benzyl, phenyl, isopropyl, tert-butyl or tert-butyl deriveding group；
NR1R2Any one in following group；
R3Any one in following group:
2. a kind of amino acid chiral ligand containing double coordination group according to claim 1, which is characterized in that described
Tert-butyl deriveding group are as follows:
The NR1R2Any one in following group:
The R3Any one in following group:
3. a kind of amino acid chiral ligand containing double coordination group according to claim 1, which is characterized in that described
Amino acid chiral ligand containing double coordination group it is specific as follows:
4. a kind of preparation side of amino acid chiral ligand containing double coordination group according to claim 1 to 3
Method, which comprises the following steps:
Step 1: type I compound with acid anhydrides under a reaction condition or type I compound is reacted under b reaction condition with acyl chlorides, system
Obtain II compound of formula；
Wherein, a reaction condition are as follows: after the amount of type I compound and acid anhydrides with molar ratio for 1:1~2 is added, 160~180
Degree, it is dry stir under the conditions of react；
The b reaction condition are as follows: type I compound: acyl chlorides: alkali A is added in solvent A with molar ratio for the amount of 1:1~2:2~10
Afterwards, it is reacted under 0~25 degree, stirring condition；The alkali A is triethylamine or DIPEA；The solvent A is methylene chloride, three chloromethanes
Alkane or DMF；
Step 2: II compound of formula and R3NH2It is reacted under c reaction condition or under d reaction condition, III compound of formula is made；
Wherein, the c reaction condition are as follows: II compound of formula: condensing agent: alkali B:R3NH2It is 1:1~2:2~3:0.8 with molar ratio
~1.5 additional amount is added in solvent B, reacts under room temperature, stirring condition；Concentration of II compound of formula in solvent B
For 1~10mol/L；The solvent B is methylene chloride or DMAC N,N' dimethyl acetamide；The condensing agent is HBTU or HATU；Institute
Stating alkali B is DIPEA or triethylamine；
Wherein, the d reaction condition are as follows: II compound of formula: oxalyl chloride or thionyl chloride are the additional amount of 1:5~10 with molar ratio
It is added in solvent C, DMF is added as catalyst, after being reacted under room temperature, stirring condition, is spin-dried for, intermediate product is made；It is described
Solvent C is methylene chloride, and the additional amount of the DMF is 1~10 drop；Concentration of II compound of formula in solvent C be 1~
10mol/L；
Then again by intermediate product, R3NH2And triethylamine is added jointly in solvent D, is reacted under room temperature, stirring condition, is made
III compound of formula；The R3NH2: triethylamine: the molar ratio of II compound of formula is 0.8~1.5:3~5:1；The solvent D is two
Chloromethanes.
5. a kind of amino acid chiral catalyst containing double coordination group, which is characterized in that have the following structure general formula:
R, R of IV compound of formula3、NR1R2With III compound R of formula, R3、NR1R2Correspondence is identical.
6. a kind of amino acid chiral catalyst containing double coordination group according to claim 5, which is characterized in that institute
It states R and is selected from one of following group:
The NR1R2Selected from one of following group:
The R3Selected from one of following group:
7. a kind of amino acid chiral Ir (III) catalyst containing double coordination group according to claim 5, feature
It is, specifically:
8. according to a kind of preparation side of any amino acid chiral catalyst containing double coordination group of claim 5-7
Method, which is characterized in that using III compound of formula prepare the amino acid chiral catalyst containing double coordination group, specifically include with
Lower step: by III compound of formula, [Cp*IrCl2]2, alkali C be added in solvent E, reacted under room temperature to 40 degree, stirring condition,
Column chromatography method obtains IV compound of formula；
9. the preparation method of chiral catalyst according to claim 8, it is characterised in that: III compound of formula: [Cp*
IrCl2]2: additional amount of the alkali C with molar ratio for 1:0.4~0.5:3~10 is added in solvent E；The alkali C is potassium carbonate, carbon
Sour sodium, cesium carbonate or lithium carbonate；The solvent E is dichloromethane or chloroform；III compound of formula is dense in solvent E
Degree is 1~10mol/L.
10. according to a kind of application of any amino acid chiral catalyst containing double coordination group of claim 5-7,
It is characterized in that, IV compound of formula is used for the asymmetry catalysis of following reaction, specifically includes the following steps: formula IV compound:
Additional amount of the Formula V compound with molar ratio for 1:50~100 is added in solvent F, under 0~40 degree, stirring condition react 1~
24 hours, VI compound of formula is made；The solvent F is in hexafluoroisopropanol, trifluoroethanol, hexafluoroisopropanol or trifluoroethanol
The molar ratio of a kind of mixed solvent with water, the hexafluoroisopropanol or trifluoroethanol and water is 1:0~10；The formula IV chemical combination
Concentration of the object in solvent F is 0.1~1mol/L；
The R5Selected from one of aryl, alkyl, alkenyl or alkynyl.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111170918A (en) * | 2020-01-21 | 2020-05-19 | 山东大学 | Method for synthesizing gamma-lactam and delta-lactam through C-H amine |
| CN113683553A (en) * | 2021-08-18 | 2021-11-23 | 扬州大学 | Chiral amide compound and synthesis method thereof |
| CN114105793A (en) * | 2021-12-03 | 2022-03-01 | 广东莱佛士制药技术有限公司 | Method for obtaining high-selectivity beta-chiral branched chain chiral amino acid |
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2019
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111170918A (en) * | 2020-01-21 | 2020-05-19 | 山东大学 | Method for synthesizing gamma-lactam and delta-lactam through C-H amine |
| CN111170918B (en) * | 2020-01-21 | 2021-09-21 | 山东大学 | Method for synthesizing gamma-lactam and delta-lactam through C-H amine |
| CN113683553A (en) * | 2021-08-18 | 2021-11-23 | 扬州大学 | Chiral amide compound and synthesis method thereof |
| CN114105793A (en) * | 2021-12-03 | 2022-03-01 | 广东莱佛士制药技术有限公司 | Method for obtaining high-selectivity beta-chiral branched chain chiral amino acid |
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