CN117603268A - Azaphosphine bidentate ligand with axial chirality and phosphine center chirality and preparation method thereof - Google Patents
Azaphosphine bidentate ligand with axial chirality and phosphine center chirality and preparation method thereof Download PDFInfo
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- CN117603268A CN117603268A CN202311321807.0A CN202311321807A CN117603268A CN 117603268 A CN117603268 A CN 117603268A CN 202311321807 A CN202311321807 A CN 202311321807A CN 117603268 A CN117603268 A CN 117603268A
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- phosphine
- chloroform
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- benzoxazole
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- 239000003446 ligand Substances 0.000 title claims abstract description 42
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- YQMDBOZKFVFKPJ-UHFFFAOYSA-N azaphosphinine Chemical compound C1=CC=PN=C1 YQMDBOZKFVFKPJ-UHFFFAOYSA-N 0.000 title description 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 78
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000000034 method Methods 0.000 claims abstract description 37
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical group C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims abstract description 29
- 150000004714 phosphonium salts Chemical group 0.000 claims abstract description 27
- KUXDQQMEFBFTGX-UHFFFAOYSA-N [N].P Chemical compound [N].P KUXDQQMEFBFTGX-UHFFFAOYSA-N 0.000 claims abstract description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 9
- 150000008300 phosphoramidites Chemical class 0.000 claims abstract description 9
- 239000000654 additive Substances 0.000 claims abstract description 7
- 230000000996 additive effect Effects 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000004440 column chromatography Methods 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 239000011261 inert gas Substances 0.000 claims abstract description 4
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 239000011593 sulfur Substances 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- -1 tert-butylmethylene, 3-pentyl Chemical group 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 4
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical group Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 claims description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims description 2
- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000005587 carbonate group Chemical group 0.000 claims 1
- 229910052763 palladium Inorganic materials 0.000 abstract description 3
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 90
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
- 238000012512 characterization method Methods 0.000 description 30
- 239000003208 petroleum Substances 0.000 description 30
- 239000007787 solid Substances 0.000 description 25
- 241000761456 Nops Species 0.000 description 14
- 239000003921 oil Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000009920 chelation Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- YMJAIEYASUCCMJ-UHFFFAOYSA-N (1-isoquinolin-1-ylnaphthalen-2-yl)-diphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CN=1)C1=CC=CC=C1 YMJAIEYASUCCMJ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 150000004074 biphenyls Chemical class 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 238000007832 transition metal-catalyzed coupling reaction Methods 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
- C07F9/65324—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
- C07F9/5325—Aromatic phosphine oxides or thioxides (P-C aromatic linkage)
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
- C07F9/6539—Five-membered rings
- C07F9/6541—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
-
- 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 & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a nitrogen-phosphine bidentate ligand with axial chirality and phosphine center chirality and a preparation method thereof, wherein the preparation method comprises the following steps: mixing and reacting alkali, a catalyst, chiral phosphoramidite ligand, an additive, quaternary phosphonium salt, benzoxazole/benzothiazole and a solvent; after the reaction under the protection of inert gas is finished, adding sulfur, and continuing the reaction under the protection of inert gas at normal temperature; filtering, concentrating and performing column chromatography to obtain a nitrogen-phosphine bidentate ligand containing axial chirality and phosphine center chirality; the method adopts quaternary phosphonium salt and benzoxazole/benzothiazole as raw materials, palladium and chiral phosphoramidite ligand as a catalytic system, and the nitrogen-phosphine bidentate ligand with axial chirality and phosphine center chirality is obtained under mild conditions with higher yield and enantioselectivity.
Description
Technical Field
The invention relates to the field of chiral phosphine compound preparation, in particular to a nitrogen-phosphine bidentate ligand containing axial chirality and phosphine center chirality and a preparation method thereof.
Background
Chiral phosphine compounds are a very important chiral ligand and a very important chiral organic catalyst in metal-catalyzed asymmetric synthesis. The phosphine ligands which are most widely applied at present and mainly based on axial chirality, carbon center chirality and spiro chirality, such as common binaphthyl ligands, biphenyls ligands, spiro ligands and carbon center chiral phosphine ligands, have important research significance and economic value in chiral medicine and material synthesis.
The design of novel axial chiral nitrogen phosphine ligand of synthetic skeleton is one of important research directions in the field of asymmetric catalysis. In 1991, the first axis chiral nitrogen phosphine ligand, QUINAP, was synthesized and researchers developed Quinazalinap, pyPhos and StackPhos et al ligands in succession. At present, the method for synthesizing the ligand is limited to two methods, a racemization framework is synthesized through coupling of two aryl units, the equivalent chiral Pd compound and the ligand are utilized to carry out chelation, kinetic resolution is carried out, then Pd chelation units are removed, and the nitrogen-phosphine ligand is released; by asymmetric transition metal catalyzed coupling reactions, the resulting ligands themselves have good coordination ability, which can poison transition metal catalysts during the reaction, and thus success is rare.
Disclosure of Invention
The invention aims to provide a nitrogen-phosphine bidentate ligand containing axial chirality and phosphine center chirality and a preparation method thereof, wherein quaternary phosphonium salt and benzoxazole/benzothiazole are adopted as raw materials, palladium and chiral phosphoramidite ligand are adopted as a catalytic system, and the nitrogen-phosphine bidentate ligand with the axial chirality and P-center chirality is obtained under mild conditions with higher yield and enantioselectivity, so that asymmetric reaction of carbon-phosphine bonds is realized.
In order to achieve the above object, the present invention provides a nitrogen-phosphine bidentate ligand having both axial chirality and phosphine center, wherein the structural formula of the nitrogen-phosphine bidentate ligand having both axial chirality and phosphine center is as follows:
wherein R is H, alkyl, aryl, or alkyl with functional groups;
R 1 and R is 2 Respectively alkyl;
R 3 is benzoxazole or benzothiazole containing substituent groups.
Preferably, R 1 And R is 2 Methyl, ethyl, isopropyl, isobutyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, tert-butylmethylene, 3-pentyl, epoxyhexyl or 3-methoxypropyl, respectively;
preferably, R 3 The structural formula is as follows:
the invention also provides a preparation method of the nitrogen-phosphine bidentate ligand with axial chirality and phosphine center, which comprises the following steps:
(1) Mixing and reacting alkali, a catalyst, chiral phosphoramidite ligand, an additive, quaternary phosphonium salt, benzoxazole/benzothiazole and a solvent;
(2) Adding sulfur, and mixing and reacting under the protection of inert gas;
(3) Filtering, concentrating and performing column chromatography to obtain a nitrogen-phosphine bidentate ligand containing axial chirality and phosphine center chirality; wherein, the reaction route formula is as follows:
preferably, in step (1), the conditions of the mixing reaction include a temperature of 40-50 ℃; and/or
The time is 30-42h;
preferably, in step (2), the conditions of the mixing reaction include a temperature of 24-26 ℃; and/or
The time is 110-130min.
Preferably, R in the quaternary phosphonium salt and benzoxazole/benzothiazole is H, alkyl, aryl or alkyl with functional groups;
R 1 and R is 2 Respectively alkyl;
preferably, R 1 And R is 2 Methyl, ethyl, isopropyl, isobutyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, tert-butylmethylene, 3-pentyl, epoxyhexyl or 3-methoxypropyl, respectively.
Preferably, the benzoxazole or benzothiazole is a benzoxazole or benzothiazole containing substituents.
Preferably, the catalyst is allyl palladium chloride dimer, palladium acetate, palladium trifluoroacetate, palladium chloride or Pd 2 (dba) 3 One of them.
Preferably, the base is a carbonate, phosphate, triethylamine or 1, 8-diazabicyclo [5.4.0] undec-7-ene;
preferably, the base is cesium carbonate or potassium phosphate;
preferably, the additive is one of cuprous chloride, cuprous bromide or cuprous iodide.
Preferably, the solvent is one of t-butyl methyl ether, 2-methyltetrahydrofuran, THF or DME.
Preferably, the chiral phosphoramidite ligand has the structural formula:
wherein R is 4 Is isopropyl or cyclohexyl.
Preferably, the following raw materials are mixed according to the following proportion:
quaternary phosphonium salts: benzoxazole or benzothiazole: catalyst: chiral phosphoramidite ligands: additive: alkali: solvent = 1 mmol: 0.1-10 mmol: 0.01-1 mmol: 0.1-5 mmol: 0-100 ml.
In the technical scheme, the method of asymmetrically breaking the carbon phosphine bond by palladium catalysis is adopted for the first time, so that the coupling reaction of the quaternary phosphonium salt and the benzoxazole or benzothiazole is realized, the reaction has higher enantioselectivity and higher yield, and the product can be used as a chiral catalyst for catalyzing the asymmetric reaction.
The invention also has the following advantages: 1) The reaction condition is simple and mild; 2) The product is easy to separate and purify; 3) The reaction has good yield and higher enantioselectivity and diastereoselectivity; 4) The product contains both axial chirality and phosphine center chirality. The yield of the corresponding nitrogen-phosphine bidentate ligand obtained by the invention is 45-98%, up to >99% ee, >25:1dr.
Additional features and advantages of the invention will be set forth in the detailed description which follows.
Drawings
The accompanying drawings are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification, illustrate the invention and together with the description serve to explain, without limitation, the invention. In the drawings:
FIG. 1 is a reaction scheme of example 1 of the present invention;
FIG. 2 is a reaction scheme of example 2 of the present invention;
FIG. 3 is a reaction scheme of example 3 of the present invention;
FIG. 4 is a reaction scheme of example 4 of the present invention;
FIG. 5 is a reaction scheme of example 5 of the present invention;
FIG. 6 is a reaction scheme of example 6 of the present invention;
FIG. 7 is a reaction scheme of example 7 of the present invention;
FIG. 8 is a reaction scheme of example 8 of the present invention;
FIG. 9 is a reaction scheme of example 9 of the present invention;
FIG. 10 is a reaction scheme of example 10 of the present invention;
FIG. 11 is a reaction scheme of example 11 of the present invention;
FIG. 12 is a reaction scheme of example 12 of the present invention;
FIG. 13 is a reaction scheme of example 13 of the present invention;
FIG. 14 is a reaction scheme of example 14 of the present invention;
FIG. 15 is a reaction scheme of example 15 of the present invention;
FIG. 16 is a reaction scheme of example 16 of the present invention;
FIG. 17 is a reaction scheme of example 17 of the present invention;
FIG. 18 is a reaction scheme of example 18 of the present invention;
FIG. 19 is a reaction scheme of example 19 of the present invention;
FIG. 20 is a reaction scheme of example 20 of the present invention;
FIG. 21 is a reaction scheme of example 21 of the present invention;
FIG. 22 is a reaction scheme of example 22 of the present invention;
FIG. 23 is a reaction scheme of example 23 of the present invention;
FIG. 24 is a reaction scheme of example 24 of the present invention;
FIG. 25 is a reaction scheme of example 25 of the present invention;
FIG. 26 is a reaction scheme of example 26 of the present invention;
FIG. 27 is a reaction scheme of example 27 of the present invention;
FIG. 28 is a reaction scheme of example 28 of the present invention;
FIG. 29 is a reaction scheme of example 29 of the present invention;
FIG. 30 is a reaction scheme of example 30 in the present invention.
Detailed Description
The invention will be further illustrated with reference to specific examples. It is to be understood that these examples are for illustration of the invention only and are not intended to limit the scope of the invention. Further, it is understood that various changes and modifications may be made by those skilled in the art after reading the teachings of the present invention, and such equivalents are intended to fall within the scope of the claims appended hereto.
Example 1
Adding cesium carbonate into a reaction tube, sealing the system, vacuumizing, and baking by a hot air gun to remove water in the cesium carbonate; after the reaction tube is cooled to room temperature, sequentially adding palladium acetate, chiral ligand, cuprous bromide, quaternary phosphonium salt, tertiary butyl methyl ether and benzoxazole or benzothiazole into the reaction system, and finally reacting for 36 hours in a 45-degree oil bath kettle; after the reaction is finished, adding sulfur into a reaction bottle, and then reacting for 2 hours at room temperature under the protection of nitrogen; filtering, concentrating and carrying out column chromatography to obtain the chiral nitrogen-phosphine bidentate ligand. The reaction scheme is shown in FIG. 1.
The product characterization data are as follows: white solid, R f ＝0.53(petroleum ether/ethyl acetate＝5:1),79％yield,95％ee,M.p.124℃. 1 H NMR(600MHz,Chloroform-d)δ8.63(d,J＝8.7Hz,1H),8.52(dd,J＝11.5,9.4Hz,1H),8.16(d,J＝8.7Hz,1H),8.11(d,J＝8.7Hz,1H),7.96(d,J＝8.0Hz,2H),7.56(d,J＝7.1Hz,2H),7.50(t,J＝7.0Hz,1H),7.38(t,J＝7.5Hz,1H),7.28-7.15(m,4H),7.12(t,J＝7.6Hz,1H),6.85(d,J＝8.0Hz,1H),0.85(d,J＝16.5Hz,9H),0.72(d,J＝12.7Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.6,150.4,141.3,139.5(d,J＝4.9Hz),137.0(d,J＝4.3Hz),135.1,134.1,133.92,133.89(d,J＝10.1Hz),130.7(d,J＝12.4Hz),129.7,129.0(d,J＝68.2Hz),128.42,128.39,128.2,127.9,127.8,127.58,127.55(d,J＝9.7Hz),127.3,127.1,126.0,125.3,124.9,124.7,120.1,110.2,36.1(d,J＝49.8Hz),24.8,15.0(d,J＝52.1Hz). 31 P NMR(243MHz,Chloroform-d)δ61.11.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.51min,t(major)＝8.33min.[α] D 25 ＝+76.0(c＝0.658,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 29 NOPS + [M+H] + 506.1712；found:506.1712.
Example 2
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 2.
The product characterization data are as follows: yellow solid, R f ＝0.39(petroleum ether/ethyl acetate＝5:1),79％yield,93％ee,M.p.106-107℃. 1 H NMR(600MHz,Chloroform-d)δ8.62(d,J＝8.6Hz,1H),8.52(dd,J＝11.3,9.2Hz,1H),8.14(d,J＝8.7Hz,1H),8.11(d,J＝8.8Hz,1H),7.97(t,J＝8.4Hz,2H),7.56(t,J＝7.4Hz,1H),7.52(t,J＝7.3Hz,1H),7.43(d,J＝8.0Hz,1H),7.39(t,J＝7.6Hz,1H),7.24-7.18(m,2H),7.17(d,J＝8.2Hz,1H),7.01(d,J＝7.9Hz,1H),6.61(s,1H),2.32(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.7Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.2,150.8,139.6(d,J＝4.6Hz),139.2,136.7(d,J＝2.7Hz),136.0,135.2,134.1,134.00(d,J＝2.7Hz),133.97(d,J＝6.2Hz),130.8(d,J＝12.6Hz),129.7,129.1(d,J＝67.9Hz),128.42,128.36,128.2,127.91,127.86,127.6,127.53,127.46,127.1,126.1,126.0,125.1,119.5,110.3,36.1(d,J＝49.8Hz),24.9,21.8,15.1(d,J＝51.9Hz). 31 P NMR(243MHz,Chloroform-d)δ61.20.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.61min,t(major)＝7.98min.[α] D 25 ＝+71.8(c＝0.265,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 31 NOPS + [M+H] + 520.1858；found:520.1861.
Example 3
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 3.
The product characterization data are as follows: white solid, R f ＝0.54(petroleum ether/ethyl acetate＝5:1),67％yield,91％ee,M.p.120-121℃. 1 H NMR(600MHz,Chloroform-d)δ8.62(d,J＝8.7Hz,1H),8.52(dd,J＝11.7,9.2Hz,1H),8.15(d,J＝8.7Hz,1H),8.09(d,J＝8.7Hz,1H),8.00-7.86(m,2H),7.56(t,J＝7.1Hz,1H),7.48(t,J＝7.1Hz,1H),7.40(t,J＝7.3Hz,1H),7.30(d,J＝8.4Hz,1H),7.21-7.09(m,2H),7.02(t,J＝7.7Hz,1H),6.96(d,J＝7.1Hz,1H),6.80(d,J＝7.9Hz,1H),2.30(s,3H),0.87(d,J＝16.5Hz,9H),0.72(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ161.3,150.1,140.9,139.8(d,J＝4.7Hz),137.1(d,J＝3.7Hz),135.3,134.12(d,J＝2.1Hz),134.09,134.0(d,J＝10.6Hz),130.9(d,J＝12.5Hz),130.8,129.6,128.9(d,J＝67.8Hz),128.34,128.30,128.2,127.8,127.7,127.4(d,J＝12.2Hz),127.3,127.0,125.8,125.1,125.03,124.97,107.5,36.2(d,J＝49.8Hz),25.0(d,J＝2.1Hz),16.0,15.2(d,J＝52.2Hz). 31 P NMR(243MHz,Chloroform-d)δ61.09.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.62min,t(major)＝5.06min.[α] D 25 ＝+80.5(c＝0.605,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 31 NOPS + [M+H] + 520.1858；found:520.1865.
Example 4
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 4.
The product characterization data are as follows: white solid, R f ＝0.53(petroleum ether/ethyl acetate＝5:1),78％yield,91％ee,M.p.126-127℃. 1 H NMR(600MHz,Chloroform-d)δ8.61(d,J＝8.7Hz,1H),8.52(dd,J＝11.9,9.0Hz,1H),8.15(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.96(d,J＝8.1Hz,2H),7.56(t,J＝7.4Hz,1H),7.50(t,J＝7.2Hz,1H),7.38(t,J＝7.6Hz,1H),7.33(s,1H),7.25-7.12(m,3H),6.93(d,J＝8.2Hz,1H),6.73(d,J＝8.3Hz,1H),2.35(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.7,148.7,141.5,139.5(d,J＝4.6Hz),136.8(d,J＝3.1Hz),135.2,134.5,134.1,134.0,133.9(d,J＝7.4Hz),130.8(d,J＝12.3Hz),129.7,129.0(d,J＝68.8Hz),128.39,128.37,128.2,127.9,127.8,127.6,127.5,127.4,127.1,126.5,126.0,125.0,120.0,109.6,36.1(d,J＝49.9Hz),24.9,21.5,15.0(d,J＝51.6Hz). 31 P NMR(243MHz,Chloroform-d)δ61.18.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.46min,t(major)＝10.71min.[α] D 25 ＝+76.7(c＝0.482,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 31 NOPS + [M+H] + 520.1858；found:520.1863.
Example 5
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 5.
The product characterization data are as follows: y is Yellow solid,R f ＝0.38(petroleum ether/ethyl acetate＝5:1),85％yield,95％ee,M.p.128℃. 1 H NMR(600MHz,Chloroform-d)δ8.60(d,J＝8.7Hz,1H),8.52(dd,J＝11.9,9.0Hz,1H),8.15(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.96(d,J＝8.1Hz,2H),7.55(t,J＝7.3Hz,1H),7.51(t,J＝7.0Hz,1H),7.38(t,J＝7.4Hz,1H),7.20(t,J＝7.9Hz,2H),7.17(d,J＝8.4Hz,1H),7.02(s,1H),6.78-6.66(m,2H),3.76(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ163.3,157.5,145.2,142.2,139.5(d,J＝4.7Hz),136.8(d,J＝3.5Hz),135.2,134.1,134.0(d,J＝1.7Hz),133.9(d,J＝6.3Hz),130.8(d,J＝12.4Hz),129.7,129.0(d,J＝67.3Hz),128.40,128.38,128.2,127.9,127.8,127.6,127.5(d,J＝12.2Hz),127.4,127.1,125.9,125.0,114.3,110.4,102.7,55.9,36.1(d,J＝49.8Hz),24.9(d,J＝2.1Hz),15.1(d,J＝52.1Hz). 31 P NMR(243MHz,Chloroform-d)δ61.15.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.85min,t(major)＝11.06min.[α] D 25 ＝+95.9(c＝0.658,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 31 NO 2 PS + [M+H] + 536.1808；found:536.1816.
Example 6
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 6.
The product characterization data are as follows: yellow solid, R f ＝0.38(petroleum ether/ethyl acetate＝5:1),85％yield,95％ee,M.p.128℃. 1 H NMR(600MHz,Chloroform-d)δ8.60(d,J＝8.7Hz,1H),8.52(dd,J＝11.9,9.0Hz,1H),8.15(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.96(d,J＝8.1Hz,2H),7.55(t,J＝7.3Hz,1H),7.51(t,J＝7.0Hz,1H),7.38(t,J＝7.4Hz,1H),7.20(t,J＝7.9Hz,2H),7.17(d,J＝8.4Hz,1H),7.02(s,1H),6.78-6.66(m,2H),3.76(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ163.3,157.5,145.2,142.2,139.5(d,J＝4.7Hz),136.8(d,J＝3.5Hz),135.2,134.1,134.0(d,J＝1.7Hz),133.9(d,J＝6.3Hz),130.8(d,J＝12.4Hz),129.7,129.0(d,J＝67.3Hz),128.40,128.38,128.2,127.9,127.8,127.6,127.5(d,J＝12.2Hz),127.4,127.1,125.9,125.0,114.3,110.4,102.7,55.9,36.1(d,J＝49.8Hz),24.9(d,J＝2.1Hz),15.1(d,J＝52.1Hz). 31 P NMR(243MHz,Chloroform-d)δ61.15.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.85min,t(major)＝11.06min.[α] D 25 ＝+95.9(c＝0.658,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 31 NO 2 PS + [M+H] + 536.1808；found:536.1816.
Example 7
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 7.
The product characterization data are as follows: yellow solid, R f ＝0.39(petroleum ether/ethyl acetate＝5:1),70％yield,97％ee,M.p.119℃. 1 H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.8,9.0Hz,1H),8.16(d,J＝8.7Hz,1H),8.10(d,J＝8.7Hz,1H),7.97(t,J＝7.0Hz,2H),7.66(s,1H),7.58(t,J＝7.4Hz,1H),7.51(t,J＝7.3Hz,1H),7.39(t,J＝7.6Hz,1H),7.28-7.17(m,3H),7.14(d,J＝8.5Hz,1H),6.79(d,J＝8.6Hz,1H),0.86(d,J＝16.5Hz,9H),0.72(d,J＝12.7Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ163.7,149.4,143.0,139.3(d,J＝4.9Hz),137.5(d,J＝3.0Hz),135.1,134.3,133.9,133.8(d,J＝10.3Hz),130.7(d,J＝12.2Hz),129.8,129.0(d,J＝68.3Hz),128.7,128.5,128.3,128.2,127.94,127.89,127.7,127.6,127.2,127.1,125.8,124.4,123.1,117.4,111.4,36.2(d,J＝49.8Hz),24.9,15.2(d,J＝51.8Hz). 31 P NMR(243MHz,Chloroform-d)δ60.94.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.88min,t(major)＝10.51min.[α] D 25 ＝+76.7(c＝0.569,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 28 NOPS 79 Br + [M+H] + 584.0807；found:584.0808.
Example 8
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 8.
The product characterization data are as follows: white solid, R f ＝0.56(petroleum ether/ethyl acetate＝5:1),72％yield,96％ee,M.p.125-126℃. 1 H NMR(600MHz,Chloroform-d)δ8.58(d,J＝8.7Hz,1H),8.50(dd,J＝11.9,9.0Hz,1H),8.16(d,J＝8.7Hz,1H),8.11(d,J＝8.8Hz,1H),8.03-7.88(m,2H),7.57(t,J＝7.0Hz,1H),7.54-7.47(m,2H),7.39(t,J＝7.2Hz,1H),7.25-7.17(m,2H),7.14(d,J＝8.4Hz,1H),7.10(dd,J＝8.6,1.9Hz,1H),6.83(d,J＝8.6Hz,1H),0.86(d,J＝16.5Hz,9H),0.72(d,J＝12.7Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ163.9,148.9,142.5,139.3(d,J＝5.0Hz),137.5(d,J＝2.0Hz),135.1,134.3,133.9,133.8(d,J＝10.8Hz),130.7(d,J＝12.4Hz),130.1,129.8,129.0(d,J＝66.2Hz),128.6,128.5,128.2,127.92,127.88,127.7,127.6,127.2,127.1,125.8,125.6,124.4,120.0,110.9,36.1(d,J＝49.9Hz),24.9,15.1(d,J＝52.3Hz). 31 P NMR(243MHz,Chloroform-d)δ60.96.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.66min,t(major)＝9.70min.[α] D 25 ＝+41.7(c＝0.895,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 28 NOPS 35 Cl + [M+H] + 540.1312；found:540.1321.
Example 9
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 9.
The product characterization data are as follows: white solid, R f ＝0.37(petroleum ether/ethyl acetate＝5:1),84％yield,94％ee,M.p.128-129℃. 1 H NMR(600MHz,Chloroform-d)δ8.63(d,J＝8.7Hz,1H),8.51(dd,J＝11.7,9.1Hz,1H),8.18(d,J＝8.7Hz,1H),8.14(d,J＝8.7Hz,1H),7.99(t,J＝8.8Hz,2H),7.94(d,J＝8.3Hz,1H),7.64-7.46(m,4H),7.40(t,J＝7.4Hz,1H),7.25-7.18(m,2H),7.15(d,J＝8.5Hz,1H),3.88(s,3H),0.85(d,J＝16.5Hz,9H),0.74(d,J＝12.7Hz,3H). 13 CNMR(151MHz,Chloroform-d)δ166.5,165.3,150.1,145.2,139.2(d,J＝4.6Hz),137.8(d,J＝3.3Hz),135.1,134.4,133.9(d,J＝2.0Hz),133.8(d,J＝10.3Hz),130.7(d,J＝12.3Hz),129.9,129.1(d,J＝67.4Hz),128.8,128.5,128.2,128.1,127.9,127.83(d,J＝12.1Hz),127.77,127.3,127.2,126.4,126.0,124.4,119.7,111.9,52.4,36.1(d,J＝49.8Hz),24.9,15.2(d,J＝52.4Hz). 31 P NMR(243MHz,Chloroform-d)δ60.83.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.88min,t(major)＝8.33min.[α] D 25 ＝+78.4(c＝0.725,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 34 H 31 NO 3 PS + [M+H] + 564.1757；found:564.1760.
Example 10
The procedure of example 1 was followed, except that the benzoxazole was selected differently. The reaction scheme is shown in FIG. 10.
The product characterization data are as follows: white solid, R f ＝0.37(petroleum ether/ethyl acetate＝5:1),84％yield,94％ee,M.p.128-129℃. 1 H NMR(600MHz,Chloroform-d)δ8.63(d,J＝8.7Hz,1H),8.51(dd,J＝11.7,9.1Hz,1H),8.18(d,J＝8.7Hz,1H),8.14(d,J＝8.7Hz,1H),7.99(t,J＝8.8Hz,2H),7.94(d,J＝8.3Hz,1H),7.64-7.46(m,4H),7.40(t,J＝7.4Hz,1H),7.25-7.18(m,2H),7.15(d,J＝8.5Hz,1H),3.88(s,3H),0.85(d,J＝16.5Hz,9H),0.74(d,J＝12.7Hz,3H). 13 CNMR(151MHz,Chloroform-d)δ166.5,165.3,150.1,145.2,139.2(d,J＝4.6Hz),137.8(d,J＝3.3Hz),135.1,134.4,133.9(d,J＝2.0Hz),133.8(d,J＝10.3Hz),130.7(d,J＝12.3Hz),129.9,129.1(d,J＝67.4Hz),128.8,128.5,128.2,128.1,127.9,127.83(d,J＝12.1Hz),127.77,127.3,127.2,126.4,126.0,124.4,119.7,111.9,52.4,36.1(d,J＝49.8Hz),24.9,15.2(d,J＝52.4Hz). 31 P NMR(243MHz,Chloroform-d)δ60.83.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.88min,t(major)＝8.33min.[α] D 25 ＝+78.4(c＝0.725,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 34 H 31 NO 3 PS + [M+H] + 564.1757；found:564.1760.
Example 11
The procedure of example 1 was followed, except that benzothiazole selection was varied. The reaction scheme is shown in FIG. 11.
The product characterization data are as follows: white solid, R f ＝0.54(petroleum ether/ethyl acetate＝5:1),57％yield,94％ee,M.p.128℃. 1 H NMR(600MHz,Chloroform-d)δ8.61(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.1Hz,1H),8.24-8.09(m,2H),8.02(d,J＝8.1Hz,1H),7.97(d,J＝7.9Hz,2H),7.59(t,J＝7.3Hz,1H),7.57-7.49(m,2H),7.43-7.33(m,2H),7.29(t,J＝7.5Hz,1H),7.23(t,J＝7.5Hz,1H),7.20(d,J＝8.5Hz,1H),7.17(d,J＝8.4Hz,1H),0.82(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ166.3,152.2,137.9(d,J＝4.4Hz),136.2,135.9(d,J＝2.1Hz),134.9,134.4(d,J＝10.0Hz),134.1,133.7,131.8,131.7(d,J＝12.4Hz),131.2(d,J＝66.4Hz),129.7,128.5,128.41,128.36,128.23,128.2,128.0,127.71,127.66,127.3,127.1,126.3,125.3,123.2,121.3,36.4(d,J＝49.5Hz),25.0,15.0(d,J＝52.6Hz). 31 P NMR(243MHz,Chloroform-d)δ61.49.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.78min,t(major)＝13.90min.[α] D 25 ＝+69.5(c＝0.380,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 29 NPS 2 + [M+H] + 522.1474；found:522.1477.
Example 12
The procedure of example 1 was followed, except that benzothiazole selection was varied. The reaction scheme is shown in FIG. 12.
The product characterization data are as follows: white solid, R f ＝0.61(petroleum ether/ethyl acetate＝5:1),50％yield,96％ee,M.p.140℃. 1 H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.0Hz,1H),8.15(d,J＝8.0Hz,2H),8.10(s,1H),8.02(d,J＝8.2Hz,1H),7.97(d,J＝8.1Hz,1H),7.63-7.49(m,2H),7.43-7.36(m,2H),7.34(d,J＝8.5Hz,1H),7.29(t,J＝7.6Hz,1H),7.17(d,J＝8.5Hz,2H),0.84(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ168.0,153.4,137.7(d,J＝4.9Hz),136.2(d,J＝2.7Hz),135.0,134.8,134.3(d,J＝10.0Hz),134.1,133.9,131.8,131.7,131.4,131.3(d,J＝66.6Hz),129.8,128.54(d,J＝12.1Hz),128.46,128.42,128.35,128.3,128.2,127.8,127.7,127.2,127.0,126.0,122.4,119.9,36.5(d,J＝49.4Hz),25.0,15.1(d,J＝52.6Hz). 31 P NMR(243MHz,Chloroform-d)δ61.37.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝7.16min,t(major)＝13.87min.[α] D 25 ＝+88.9(c＝0.312,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 28 NPS 2 79 Br + [M+H] + 600.0579；found:600.0591.
Example 13
The procedure of example 1 was followed, except that benzothiazole selection was varied. The reaction scheme is shown in FIG. 13.
The product characterization data are as follows: white solid, R f ＝0.61(petroleum ether/ethyl acetate＝5:1),50％yield,96％ee,M.p.140℃. 1 H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.0Hz,1H),8.15(d,J＝8.0Hz,2H),8.10(s,1H),8.02(d,J＝8.2Hz,1H),7.97(d,J＝8.1Hz,1H),7.63-7.49(m,2H),7.43-7.36(m,2H),7.34(d,J＝8.5Hz,1H),7.29(t,J＝7.6Hz,1H),7.17(d,J＝8.5Hz,2H),0.84(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ168.0,153.4,137.7(d,J＝4.9Hz),136.2(d,J＝2.7Hz),135.0,134.8,134.3(d,J＝10.0Hz),134.1,133.9,131.8,131.7,131.4,131.3(d,J＝66.6Hz),129.8,128.54(d,J＝12.1Hz),128.46,128.42,128.35,128.3,128.2,127.8,127.7,127.2,127.0,126.0,122.4,119.9,36.5(d,J＝49.4Hz),25.0,15.1(d,J＝52.6Hz). 31 P NMR(243MHz,Chloroform-d)δ61.37.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝7.16min,t(major)＝13.87min.[α] D 25 ＝+88.9(c＝0.312,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 28 NPS 2 79 Br + [M+H] + 600.0579；found:600.0591.
Example 14
The procedure of example 1 was followed, except that benzothiazole selection was varied. The reaction scheme is shown in FIG. 14.
The product characterization data are as follows: white solid, R f ＝0.61(petroleum ether/ethyl acetate＝5:1),50％yield,96％ee,M.p.140℃. 1 H NMR(600MHz,Chloroform-d)δ8.57(d,J＝8.7Hz,1H),8.50(dd,J＝11.6,9.0Hz,1H),8.15(d,J＝8.0Hz,2H),8.10(s,1H),8.02(d,J＝8.2Hz,1H),7.97(d,J＝8.1Hz,1H),7.63-7.49(m,2H),7.43-7.36(m,2H),7.34(d,J＝8.5Hz,1H),7.29(t,J＝7.6Hz,1H),7.17(d,J＝8.5Hz,2H),0.84(d,J＝16.6Hz,9H),0.78(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ168.0,153.4,137.7(d,J＝4.9Hz),136.2(d,J＝2.7Hz),135.0,134.8,134.3(d,J＝10.0Hz),134.1,133.9,131.8,131.7,131.4,131.3(d,J＝66.6Hz),129.8,128.54(d,J＝12.1Hz),128.46,128.42,128.35,128.3,128.2,127.8,127.7,127.2,127.0,126.0,122.4,119.9,36.5(d,J＝49.4Hz),25.0,15.1(d,J＝52.6Hz). 31 P NMR(243MHz,Chloroform-d)δ61.37.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝7.16min,t(major)＝13.87min.[α] D 25 ＝+88.9(c＝0.312,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 28 NPS 2 79 Br + [M+H] + 600.0579；found:600.0591.
Example 15
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 15.
The product characterization data are as follows: white solid, R f ＝0.65(petroleum ether/ethyl acetate＝5:1),74％yield,98％ee,M.p.91-92℃. 1 H NMR(600MHz,Chloroform-d)δ8.70(dd,J＝13.8,8.9Hz,1H),8.60(d,J＝8.7Hz,1H),8.23-8.12(m,2H),7.97(d,J＝7.5Hz,2H),7.61-7.53(m,2H),7.51(t,J＝7.3Hz,1H),7.34(t,J＝7.5Hz,1H),7.25-7.17(m,3H),7.17-7.10(m,2H),6.92(d,J＝8.0Hz,1H),1.95-1.82(m,1H),1.46-1.32(m,2H),0.89(d,J＝13.2Hz,3H),0.65(d,J＝6.5Hz,3H),0.40(d,J＝6.5Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,138.9(d,J＝6.4Hz),136.8(d,J＝3.6Hz),134.6,134.3(d,J＝2.0Hz),134.2,133.6(d,J＝10.7Hz),130.2,129.9,129.3(d,J＝13.5Hz),128.5,128.4,128.2,128.07,128.01,127.9,127.8,127.2,127.0,126.0,125.4,125.2,124.7,120.2,110.4,43.4(d,J＝51.7Hz),24.1(d,J＝11.0Hz),24.0(d,J＝3.6Hz),23.9(d,J＝7.8Hz),21.7(d,J＝54.9Hz). 31 P NMR(243MHz,Chloroform-d)δ43.40.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.80min,t(major)＝7.09min.[α] D 25 ＝+29.7(c＝0.684,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 29 NOPS + [M+H] + 506.1712；found:506.1709.
Example 16
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 16.
The product characterization data are as follows: yellow solid, R f ＝0.45(petroleum ether/ethyl acetate＝5:1),65％yield,97％ee,M.p.107℃. 1 H NMR(600MHz,Chloroform-d)δ8.72(dd,J＝13.0,8.9Hz,1H),8.65(d,J＝8.7Hz,1H),8.18(d,J＝8.7Hz,1H),8.15(d,J＝8.7Hz,1H),7.98(t,J＝8.2Hz,2H),7.62-7.54(m,2H),7.51(t,J＝7.3Hz,1H),7.34(t,J＝7.5Hz,1H),7.24-7.17(m,3H),7.17-7.10(m,2H),6.87(d,J＝8.1Hz,1H),1.53-1.37(m,1H),1.33-1.15(m,5H),1.10-0.99(m,2H),0.92-0.82(m,1H),0.82-0.75(m,1H),0.72(d,J＝13.0Hz,3H),-0.35(q,J＝10.3Hz,1H). 13 C NMR(151MHz,Chloroform-d)δ162.5,150.6,141.4,139.6(d,J＝6.0Hz),136.9(d,J＝3.4Hz),134.8,134.4(d,J＝2.3Hz),134.2,133.7(d,J＝10.4Hz),130.8(d,J＝12.8Hz),129.9,128.4,128.2,128.1,128.0,127.8,127.7(d,J＝12.5Hz),127.5,127.1,126.0,125.5,124.9,124.8,120.2,110.3,40.7(d,J＝52.2Hz),25.9(d,J＝14.2Hz),25.3,25.2(d,J＝1.4Hz),24.8(d,J＝14.3Hz),24.7(d,J＝1.6Hz),17.9(d,J＝54.4Hz). 31 P NMR(243MHz,Chloroform-d)δ51.73.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.38min,t(major)＝8.04min.[α] D 25 ＝+43.9(c＝0.645,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 34 H 31 NOPS + [M+H] + 532.1858；found:532.1869.
Example 17
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 17.
The product characterization data are as follows: yellow oil, R f ＝0.39(petroleum ether/ethyl acetate＝5:1),69％yield,97％ee. 1 H NMR(600MHz,Chloroform-d)δ8.69(dd,J＝13.5,8.9Hz,1H),8.61(d,J＝8.7Hz,1H),8.19(d,J＝8.9Hz,1H),8.16(d,J＝9.0Hz,1H),7.98(t,J＝9.3Hz,2H),7.58(t,J＝7.3Hz,1H),7.54(d,J＝7.8Hz,1H),7.50(t,J＝7.3Hz,1H),7.36(t,J＝7.4Hz,1H),7.24(d,J＝8.7Hz,1H),7.22-7.16(m,2H),7.14(t,J＝7.6Hz,1H),7.11(d,J＝8.6Hz,1H),6.93(d,J＝8.0Hz,1H),1.58(dq,J＝15.0,7.4Hz,2H),0.89(d,J＝13.2Hz,3H),0.68(dt,J＝20.1,7.4Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.5,150.5,141.4,139.4(d,J＝6.5Hz),136.8(d,J＝3.5Hz),134.5,134.4(d,J＝29.7Hz),133.5(d,J＝10.3Hz),129.9,129.8(d,J＝13.2Hz),128.5,128.4(d,J＝73.4Hz),128.254,128.250(d,J＝12.2Hz),128.12,128.05,128.0,127.9,127.2,126.9,126.0,125.5,125.1,124.7,120.2,110.3,28.7(d,J＝54.5Hz),20.1(d,J＝55.8Hz),6.4(d,J＝4.5Hz). 31 P NMR(243MHz,Chloroform-d)δ46.76.The enantiomeric excess was determined by Daicel Chiralpak AD-H,n-hexane/isopropanol＝80/20,1mL/min,λ＝254nm,t(minor)＝6.40min,t(major)＝13.96min.[α] D 25 ＝+44.4(c＝0.342,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 30 H 25 NOPS + [M+H] + 478.1389；found:478.1396.
Example 18
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 18.
The product characterization data are as follows: yellow solid, R f ＝0.60(petroleum ether/ethyl acetate＝5:1),70％yield,94％ee,M.p.118℃. 1 H NMR(600MHz,Chloroform-d)δ8.79(dd,J＝13.3,8.9Hz,1H),8.60(d,J＝8.7Hz,1H),8.18(d,J＝8.7Hz,1H),8.15(d,J＝8.7Hz,1H),7.98(t,J＝7.4Hz,2H),7.59-7.53(m,2H),7.51(t,J＝7.0Hz,1H),7.33(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.17-7.10(m,2H),6.91(d,J＝8.0Hz,1H),1.63-1.46(m,3H),1.46-1.38(m,1H),1.37-1.29(m,1H),1.30-1.22(m,1H),1.21-1.11(m,1H),0.73(d,J＝13.1Hz,3H),0.69-0.59(m,1H),0.52-0.32(m,1H). 13 C NMR(151MHz,Chloroform-d)δ162.6,150.5,141.3,139.0(d,J＝6.3Hz),137.0(d,J＝3.1Hz),134.8,134.4(d,J＝2.2Hz),134.2,133.6(d,J＝10.6Hz),130.4(d,J＝13.0Hz),129.9,128.8(d,J＝72.5Hz),128.4,128.2,128.1,128.0(d,J＝12.4Hz),127.9,127.8,127.1,126.0,125.5,124.81,124.76,120.1,110.3,41.7(d,J＝55.1Hz),27.0,26.3,25.5(d,J＝11.7Hz),25.2(d,J＝12.3Hz),19.4(d,J＝55.5Hz). 31 P NMR(243MHz,Chloroform-d)δ51.43.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.84min,t(major)＝7.34min.[α] D 25 ＝+70.8(c＝0.694,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 29 NOPS + [M+H] + 518.1702；found:518.1702.
Example 19
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 19.
The product characterization data are as follows: white solid, R f ＝0.63(petroleum ether/ethyl acetate＝5:1),82％yield,98％ee,M.p.110-111℃. 1 H NMR(600MHz,Chloroform-d)δ8.61(d,J＝8.7Hz,1H),8.58(dd,J＝12.6,9.0Hz,1H),8.17(d,J＝8.8Hz,1H),8.15(d,J＝8.7Hz,1H),8.02-7.93(m,2H),7.61-7.54(m,2H),7.51(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.28-7.07(m,5H),6.87(d,J＝8.0Hz,1H),1.63-1.54(m,1H),1.47-1.19(m,6H),1.19-1.06(m,3H),1.05-0.92(m,2H),0.74(d,J＝12.7Hz,3H),0.59-0.46(m,1H). 13 C NMR(151MHz,Chloroform-d)δ162.5,150.6,141.4,139.4(d,J＝5.9Hz),136.9(d,J＝4.2Hz),134.6,134.22,134.18(d,J＝2.1Hz),133.8(d,J＝10.4Hz),129.9,129.8(d,J＝12.5Hz),128.8(d,J＝71.8Hz),128.5,128.2,128.1,128.03,128.01,127.8,127.10,127.05,125.9,125.4,125.0,124.7,120.2,110.3,42.5(d,J＝49.7Hz),27.9,27.5,27.3(d,J＝15.7Hz),27.2,26.8,26.7(d,J＝16.7Hz),17.4(d,J＝53.6Hz). 31 PNMR(243MHz,Chloroform-d)δ54.04.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.91min,t(major)＝8.41min.[α] D 25 ＝+62.9(c＝0.735,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 35 H 33 NOPS + [M+H] + 546.2015；found:546.2020.
Example 20
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 20.
The product characterization data are as follows: white solid, R f ＝0.68(petroleum ether/ethyl acetate＝5:1),77％yield,99％ee,M.p.96-97℃. 1 H NMR(600MHz,Chloroform-d)δ8.81(dd,J＝14.0,8.9Hz,1H),8.63(d,J＝8.7Hz,1H),8.24-8.12(m,2H),7.98(d,J＝8.1Hz,2H),7.60-7.52(m,2H),7.51(t,J＝7.3Hz,1H),7.33(t,J＝7.5Hz,1H),7.24-7.16(m,3H),7.16-7.10(m,2H),6.93(d,J＝8.0Hz,1H),1.50-1.44(m,2H),0.93(d,J＝13.3Hz,3H),0.73(s,9H). 13 C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.5,138.3(d,J＝6.2Hz),137.1(d,J＝3.6Hz),134.8,134.3(d,J＝2.1Hz),134.2,133.5(d,J＝10.6Hz),131.4(d,J＝73.3Hz),129.9,129.6(d,J＝13.8Hz),128.5(d,J＝12.7Hz),128.4,128.2,128.1,128.0,127.7,127.1,126.0,125.4,125.2,124.7,120.2,110.4,47.1(d,J＝49.8Hz),32.5(d,J＝4.4Hz),30.9(d,J＝7.2Hz),23.2(d,J＝54.3Hz). 31 P NMR(243MHz,Chloroform-d)δ41.40.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.54min,t(major)＝6.53min.[α] D 25 ＝+51.4(c＝0.564,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 31 NOPS + [M+H] + 520.1858；found:520.1863.
Example 21
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 21.
The product characterization data are as follows: white solid, R f ＝0.64(petroleum ether/ethyl acetate＝5:1),91％yield,97％ee,M.p.94-95℃. 1 H NMR(600MHz,Chloroform-d)δ8.73-8.54(m,2H),8.17(d,J＝8.8Hz,1H),8.15(d,J＝8.9Hz,1H),7.98(t,J＝8.1Hz,2H),7.61-7.48(m,3H),7.35(t,J＝7.5Hz,1H),7.24-7.20(m,2H),7.17(t,J＝8.0Hz,2H),7.13(t,J＝7.6Hz,1H),6.89(d,J＝8.0Hz,1H),1.46-1.04(m,5H),0.77(d,J＝12.8Hz,3H),0.60(t,J＝7.4Hz,3H),0.27(t,J＝7.1Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.4(d,J＝6.0Hz),136.9(d,J＝2.9Hz),134.6,134.2,133.8(d,J＝10.4Hz),130.0(d,J＝12.6Hz),129.8,128.9(d,J＝70.1Hz),128.4,128.14,128.09,128.02,127.99,127.8,127.1,125.9,125.4,125.0,124.7,120.2,110.3,44.1(d,J＝50.6Hz),20.8,20.6,18.4(d,J＝53.3Hz),13.6(d,J＝9.8Hz),11.5(d,J＝13.4Hz). 31 P NMR(243MHz,Chloroform-d)δ53.68.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝5.40min,t(major)＝7.08min.[α] D 25 ＝+22.8(c＝0.763,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 31 NOPS + [M+H] + 520.1858；found:520.1863.
Example 22
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 22.
The product characterization data are as follows: white solid, R f ＝0.28(petroleum ether/ethyl acetate＝5:1),51％yield,97％ee,M.p.129℃. 1 H NMR(600MHz,Chloroform-d)δ8.70(dd,J＝12.7,9.3Hz,1H),8.65(d,J＝8.7Hz,1H),8.20(d,J＝8.6Hz,1H),8.16(d,J＝8.6Hz,1H),8.00(t,J＝9.0Hz,2H),7.59(t,J＝7.3Hz,1H),7.55(d,J＝7.1Hz,2H),7.36(t,J＝7.5Hz,1H),7.29-7.12(m,5H),6.89(d,J＝7.9Hz,1H),3.75-3.56(m,1H),3.35-3.19(m,1H),2.84(t,J＝11.5Hz,1H),1.76-1.54(m,3H),1.40-1.30(m,1H),1.05(d,J＝12.1Hz,1H),0.78-0.66(m,4H). 13 C NMR(151MHz,Chloroform-d)δ162.5,150.5,141.5,139.8(d,J＝6.4Hz),136.9(d,J＝3.6Hz),134.9,134.5(d,J＝2.1Hz),134.3,133.9(d,J＝10.7Hz),130.7(d,J＝12.9Hz),130.1,128.6,128.32,128.27,128.2,128.1,127.939,127.936(d,J＝12.5Hz),127.3,127.2,126.7,126.0,125.8,125.1,124.8,120.4,110.3,67.1(d,J＝13.9Hz),66.6(d,J＝14.2Hz),38.3(d,J＝54.4Hz),25.0(d,J＝2.9Hz),24.6(d,J＝2.5Hz),17.6(d,J＝55.1Hz). 31 P NMR(243MHz,Chloroform-d)δ52.0.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.40min,t(major)＝8.95min.[α] D 25 ＝+55.1(c＝0.266,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 33 H 29 NO 2 PS + [M+H] + 534.1651；found:534.1656.
Example 23
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 23.
The product characterization data are as follows: white solid, R f ＝0.57(petroleum ether/ethyl acetate＝5:1),82％yield,96％ee,M.p.93-94℃. 1 H NMR(600MHz,Chloroform-d)δ8.77(dd,J＝13.2,8.9Hz,1H),8.62(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.8Hz,1H),8.03-7.95(m,2H),7.60-7.53(m,2H),7.51(t,J＝7.4Hz,1H),7.34(t,J＝7.6Hz,1H),7.23-7.17(m,3H),7.16-7.10(m,2H),6.89(d,J＝7.9Hz,1H),1.73-1.60(m,1H),0.81(dd,J＝18.8,6.8Hz,3H),0.76(d,J＝13.0Hz,3H),0.48(dd,J＝18.7,6.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.5,150.5,141.3,139.7(d,J＝6.2Hz),136.8(d,J＝3.3Hz),134.7,134.4(d,J＝2.2Hz),134.2,133.6(d,J＝10.1Hz),130.7(d,J＝12.5Hz),129.9,128.4,128.2,128.1,128.03,127.96,127.9,127.8,127.1,127.0,126.0,125.4,125.0,124.7,120.2,110.3,30.9(d,J＝52.9Hz),18.2(d,J＝54.2Hz),15.8,15.4. 31 PNMR(243MHz,Chloroform-d)δ55.31.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.88min,t(major)＝7.42min.[α] D 25 ＝+26.4(c＝0.707,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 31 H 27 NOPS + [M+H] + 492.1545；found:492.1558.
Example 24
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 24.
The product characterization data are as follows: yellow oil, R f ＝0.13(petroleum ether/ethyl acetate＝5:1),45％yield,97％ee. 1 H NMR(600MHz,Chloroform-d)δ8.68(dd,J＝13.6,8.8Hz,1H),8.61(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.9Hz,1H),7.98(t,J＝9.2Hz,2H),7.58(t,J＝7.4Hz,1H),7.54(d,J＝7.7Hz,1H),7.50(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.15(t,J＝7.6Hz,1H),7.10(d,J＝8.5Hz,1H),6.97(d,J＝8.1Hz,1H),2.95(s,3H),2.75-2.64(m,2H),1.79-1.57(m,3H),1.57-1.44(m,1H),0.89(d,J＝13.3Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.3(d,J＝6.5Hz),136.8(d,J＝4.1Hz),134.6,134.5,134.3,133.4(d,J＝11.2Hz),129.9,129.7(d,J＝13.4Hz),128.9,128.5,128.3(d,J＝12.6Hz),128.3,128.1,128.1,127.93,127.88,127.2,126.9,126.0,125.4,125.1,124.7,120.2,110.4,71.9(d,J＝18.0Hz),58.2,32.4(d,J＝54.6Hz),22.7,20.5(d,J＝56.1Hz). 31 P NMR(243MHz,Chloroform-d)δ44.53.The enantiomeric excess was determined by Daicel Chiralpak IC,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝14.86min,t(minor)＝17.17min.[α] D 25 ＝+28.8(c＝0.316,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 29 NO 2 PS + [M+H] + 522.1651；found:522.1651.
Example 25
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 25.
The product characterization data are as follows: yellow oil, R f ＝0.13(petroleum ether/ethyl acetate＝5:1),45％yield,97％ee. 1 H NMR(600MHz,Chloroform-d)δ8.68(dd,J＝13.6,8.8Hz,1H),8.61(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.9Hz,1H),7.98(t,J＝9.2Hz,2H),7.58(t,J＝7.4Hz,1H),7.54(d,J＝7.7Hz,1H),7.50(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.15(t,J＝7.6Hz,1H),7.10(d,J＝8.5Hz,1H),6.97(d,J＝8.1Hz,1H),2.95(s,3H),2.75-2.64(m,2H),1.79-1.57(m,3H),1.57-1.44(m,1H),0.89(d,J＝13.3Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.3(d,J＝6.5Hz),136.8(d,J＝4.1Hz),134.6,134.5,134.3,133.4(d,J＝11.2Hz),129.9,129.7(d,J＝13.4Hz),128.9,128.5,128.3(d,J＝12.6Hz),128.3,128.1,128.1,127.93,127.88,127.2,126.9,126.0,125.4,125.1,124.7,120.2,110.4,71.9(d,J＝18.0Hz),58.2,32.4(d,J＝54.6Hz),22.7,20.5(d,J＝56.1Hz). 31 P NMR(243MHz,Chloroform-d)δ44.53.The enantiomeric excess was determined by Daicel Chiralpak IC,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝14.86min,t(minor)＝17.17min.[α] D 25 ＝+28.8(c＝0.316,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 29 NO 2 PS + [M+H] + 522.1651；found:522.1651.
Example 26
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 26.
The product characterization data are as follows: yellow oil, R f ＝0.13(petroleum ether/ethyl acetate＝5:1),45％yield,97％ee. 1 H NMR(600MHz,Chloroform-d)δ8.68(dd,J＝13.6,8.8Hz,1H),8.61(d,J＝8.7Hz,1H),8.18(d,J＝8.8Hz,1H),8.16(d,J＝8.9Hz,1H),7.98(t,J＝9.2Hz,2H),7.58(t,J＝7.4Hz,1H),7.54(d,J＝7.7Hz,1H),7.50(t,J＝7.3Hz,1H),7.35(t,J＝7.6Hz,1H),7.25-7.17(m,3H),7.15(t,J＝7.6Hz,1H),7.10(d,J＝8.5Hz,1H),6.97(d,J＝8.1Hz,1H),2.95(s,3H),2.75-2.64(m,2H),1.79-1.57(m,3H),1.57-1.44(m,1H),0.89(d,J＝13.3Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.4,150.5,141.4,139.3(d,J＝6.5Hz),136.8(d,J＝4.1Hz),134.6,134.5,134.3,133.4(d,J＝11.2Hz),129.9,129.7(d,J＝13.4Hz),128.9,128.5,128.3(d,J＝12.6Hz),128.3,128.1,128.1,127.93,127.88,127.2,126.9,126.0,125.4,125.1,124.7,120.2,110.4,71.9(d,J＝18.0Hz),58.2,32.4(d,J＝54.6Hz),22.7,20.5(d,J＝56.1Hz). 31 P NMR(243MHz,Chloroform-d)δ44.53.The enantiomeric excess was determined by Daicel Chiralpak IC,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝14.86min,t(minor)＝17.17min.[α] D 25 ＝+28.8(c＝0.316,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 32 H 29 NO 2 PS + [M+H] + 522.1651；found:522.1651.
Example 27
The procedure of example 1 was followed, except that the quaternary phosphonium salt was selected differently. The reaction scheme is shown in FIG. 27.
The product characterization data are as follows: yellow solid, R f ＝0.31(petroleum ether/ethyl acetate＝5:1),77％yield,87％ee,M.p.109-110℃. 1 H NMR(600MHz,Chloroform-d)δ8.60(dd,J＝13.6,8.9Hz,1H),8.55(d,J＝8.7Hz,1H),8.15-8.07(m,2H),7.92-7.81(m,2H),7.55(d,J＝7.7Hz,1H),7.41(d,J＝8.2Hz,1H),7.33(d,J＝8.2Hz,1H),7.20(t,J＝7.4Hz,1H),7.14(t,J＝7.5Hz,1H),7.01(s,1H),6.94(d,J＝8.0Hz,1H),6.85(s,1H),2.95(s,3H),2.72-2.62(m,2H),2.27(s,3H),2.15(s,3H),1.74-1.56(m,2H),1.54-1.41(m,1H),1.24-1.15(m,1H),0.86(d,J＝13.3Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ162.7,150.5,141.5,138.7(d,J＝6.3Hz),138.0,136.9,136.3(d,J＝4.1Hz),134.8,133.7(d,J＝10.7Hz),132.9(d,J＝2.2Hz),132.7,130.8,130.2,129.6,128.8(d,J＝13.2Hz),128.07,128.05,128.0,127.9,126.8,125.7,125.3,125.1,125.0,124.6,120.1,110.4,72.0(d,J＝18.2Hz),58.2,32.4(d,J＝54.7Hz),22.7,22.11,22.09,20.5(d,J＝56.0Hz). 31 P NMR(243MHz,Chloroform-d)δ44.63.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝4.91min,t(major)＝6.40min.[α] D 25 ＝+79.7(c＝0.409,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 34 H 33 NO 2 PS + [M+H] + 550.1964；found:550.1974.
Example 28
The procedure of example 1 was followed, except that the quaternary phosphonium salt and benzoxazole were selected differently. The reaction scheme is shown in FIG. 28.
The product characterization data are as follows: white solid, R f ＝0.49(petroleum ether/ethyl acetate＝5:1),46％yield,85％ee,M.p.111℃. 1 H NMR(600MHz,Chloroform-d)δ8.55(d,J＝8.7Hz,1H),8.46(dd,J＝12.0,9.0Hz,1H),8.04(d,J＝8.7Hz,1H),8.00(d,J＝8.7Hz,1H),7.72(s,2H),7.21(d,J＝8.3Hz,1H),7.08(d,J＝8.6Hz,1H),7.07-6.99(m,3H),6.78-6.69(m,2H),3.77(s,3H),2.49(s,3H),2.46(s,3H),0.85(d,J＝16.5Hz,9H),0.71(d,J＝12.8Hz,3H). 13 C NMR(151MHz,Chloroform-d)δ163.6,157.5,145.2,142.3,139.5(d,J＝4.9Hz),138.7,137.8,136.9(d,J＝3.8Hz),134.4,134.3(d,J＝1.9Hz),133.5,132.2(d,J＝10.6Hz),130.9(d,J＝12.5Hz),130.7,129.4,129.0,127.5,127.3,127.2,127.0,126.9,126.0,124.1,114.1,110.4,102.7,56.0,36.1(d,J＝49.9Hz),24.9,21.8,21.7,15.0(d,J＝51.9Hz). 31 P NMR(243MHz,Chloroform-d)δ60.99.The enantiomeric excess was determined by Daicel Chiralpak IG,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝9.21min,t(minor)＝13.49min.[α] D 25 ＝+82.7(c＝0.222,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 35 H 35 NO 2 PS + [M+H] + 564.2121；found:564.2122.
Example 29
The procedure of example 1 was followed, except that the quaternary phosphonium salt and benzoxazole were selected differently. The reaction scheme is shown in FIG. 29.
The product characterization data are as follows: white solid, R f ＝0.73(petroleum ether/ethyl acetate＝5:1),98％yield,88％ee,M.p.137-138℃. 1 H NMR(600MHz,Chloroform-d)δ8.55(d,J＝8.7Hz,1H),8.46(dd,J＝11.9,9.1Hz,1H),8.21(s,1H),8.08(d,J＝8.7Hz,1H),8.03(d,J＝8.8Hz,1H),7.88(d,J＝8.5Hz,1H),7.69(s,2H),7.21(d,J＝8.7Hz,1H),7.15(d,J＝8.7Hz,1H),7.06(d,J＝8.7Hz,1H),7.01(d,J＝8.6Hz,1H),6.92(d,J＝8.5Hz,1H),3.89(s,3H),2.85(d,J＝7.4Hz,2H),2.81(d,J＝7.3Hz,2H),2.71-2.53(m,2H),2.13-1.96(m,4H),1.90-1.79(m,4H),1.79-1.67(m,4H),0.83(d,J＝16.5Hz,9H),0.70(d,J＝12.7Hz,3H). 13 CNMR(151MHz,Chloroform-d)δ166.6,164.2,153.3,142.3,141.6,141.2,139.2(d,J＝4.9Hz),137.7(d,J＝3.0Hz),134.6,134.2(d,J＝1.6Hz),133.6,132.4(d,J＝10.3Hz),130.8(d,J＝12.5Hz),130.1,129.3,128.8,127.6,127.17(d,J＝23.4Hz),127.16,127.1,126.6,126.5,125.8,123.4,122.1,109.9,52.4,43.1,43.0,36.9,36.8,36.1(d,J＝50.0Hz),28.5,28.39,28.36,24.9,18.49,18.45,15.1(d,J＝51.6Hz). 31 P NMR(243MHz,Chloroform-d)δ60.85.The enantiomeric excess was determined by Daicel Chiralpak IA,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(minor)＝6.05min,t(major)＝6.58min.[α] D 25 ＝+103.6(c＝0.635,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 44 H 46 NO 3 PSNa + [M+Na] + 722.2828；found:722.2834.
Example 30
The procedure of example 1 was followed, except that the quaternary phosphonium salt and benzoxazole were selected differently. The reaction scheme is shown in FIG. 30.
The product characterization data are as follows: colorless oil, R f ＝0.32(petroleum ether/ethyl acetate＝5:1),65％yield,95％ee. 1 H NMR(600MHz,Chloroform-d)δ8.42(dd,J＝15.9,7.7Hz,1H),8.27(d,J＝7.5Hz,1H),8.25(s,1H),8.01(d,J＝8.5Hz,1H),7.57-7.47(m,3H),7.46(d,J＝7.1Hz,1H),7.31(d,J＝8.5Hz,1H),3.93(s,3H),2.05(s,3H),1.96(s,3H),1.63-1.54(m,1H),1.45(t,J＝14.1Hz,1H),1.30(d,J＝13.2Hz,3H),0.76(s,9H). 13 C NMR(151MHz,Chloroform-d)δ166.7,163.7,153.3,141.9,139.8(d,J＝6.8Hz),139.6(d,J＝1.9Hz),139.5,137.4(d,J＝9.1Hz),134.0,133.0(d,J＝2.5Hz),132.8(d,J＝13.2Hz),129.0,128.4,128.0(d,J＝13.2Hz),127.3,127.2,126.3,122.4,110.3,52.4,48.0(d,J＝49.8Hz),32.6(d,J＝4.6Hz),31.1,31.0,22.8(d,J＝54.2Hz),20.7(d,J＝50.5Hz). 31 P NMR(243MHz,Chloroform-d)δ40.44.The enantiomeric excess was determined by Daicel Chiralpak IE,n-hexane/isopropanol＝70/30,1mL/min,λ＝254nm,t(major)＝8.91min,t(minor)＝10.22min.[α] D 25 ＝-52.0(c＝0.179,CH 2 Cl 2 ).HRMS(ESI)calcd for:C 29 H 33 NO 3 PS + [M+H] + 506.1913；found:506.1915.
The preferred embodiments of the present invention have been described in detail above with reference to the accompanying drawings, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.
In addition, the specific features described in the above embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, various possible combinations are not described further.
Moreover, any combination of the various embodiments of the invention can be made without departing from the spirit of the invention, which should also be considered as disclosed herein.
Claims (10)
1. A nitrogen-phosphine bidentate ligand with both axial chirality and phosphine center, which is characterized in that the structural formula of the nitrogen-phosphine bidentate ligand with both axial chirality and phosphine center is as follows:
wherein R is H, alkyl, aryl, or alkyl with functional groups;
R 1 and R is 2 Respectively alkyl;
R 3 is benzoxazole or benzothiazole containing substituent groups.
2. The nitrogen-phosphine bidentate ligand having both axial chirality and phosphine center according to claim 1, wherein R 1 And R is 2 Methyl, ethyl, isopropyl, isobutyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, tert-butylmethylene, 3-pentyl, epoxyHexyl or 3-methoxypropyl;
preferably, R 3 The structural formula is as follows:
3. a process for the preparation of a nitrogen-phosphine bidentate ligand having both axial chirality and phosphine centre as claimed in claim 1 or 2, which comprises:
(1) Mixing and reacting alkali, a catalyst, chiral phosphoramidite ligand, an additive, quaternary phosphonium salt, benzoxazole or benzothiazole and a solvent;
(2) Adding sulfur, and mixing and reacting under the protection of inert gas;
(3) Filtering, concentrating and performing column chromatography to obtain a nitrogen-phosphine bidentate ligand containing axial chirality and phosphine center chirality;
4. the production process according to claim 3, wherein, in the step (1), the conditions of the mixing reaction include a temperature of 40 to 50 ℃; and/or
The time is 30-42h;
preferably, in step (2), the conditions of the mixing reaction include a temperature of 24-26 ℃; and/or
The time is 110-130min.
5. The preparation method according to claim 3, wherein R in the quaternary phosphonium salt and the benzoxazole/benzothiazole is H, alkyl, aryl or alkyl with functional group;
preferablyGround, R 1 And R is 2 Methyl, ethyl, isopropyl, isobutyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, tert-butylmethylene, 3-pentyl, epoxyhexyl or 3-methoxypropyl, respectively.
6. A production method according to claim 3, wherein the benzoxazole or benzothiazole is a benzoxazole or benzothiazole containing a substituent.
7. The process according to claim 3, wherein the catalyst is allyl palladium chloride dimer, palladium acetate, palladium trifluoroacetate, palladium chloride or Pd 2 (dba) 3 One of them.
8. A process according to claim 3, wherein the base is carbonate, phosphate, triethylamine or 1, 8-diazabicyclo [5.4.0] undec-7-ene;
preferably, the base is cesium carbonate;
preferably, the additive is one of cuprous chloride, cuprous bromide or cuprous iodide.
Preferably, the solvent is one of t-butyl methyl ether, 2-methyltetrahydrofuran, THF or DME.
9. A method of preparation according to claim 3, wherein the chiral phosphoramidite ligand has the structural formula:
wherein R is 4 Is isopropyl or cyclohexyl.
10. The preparation method according to claim 3, wherein the raw materials are mixed according to the following proportion:
quaternary phosphonium salts: benzoxazole or benzothiazole: catalyst: chiral phosphoramidite ligands: additive: alkali: solvent = 1 mmol: 0.1-10 mmol: 0.01-1 mmol: 0.1-5 mmol: 0-100 ml.
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