CN115232163B - Silicon center chiral molecular compound and preparation method and application thereof - Google Patents

Silicon center chiral molecular compound and preparation method and application thereof Download PDF

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CN115232163B
CN115232163B CN202210800919.3A CN202210800919A CN115232163B CN 115232163 B CN115232163 B CN 115232163B CN 202210800919 A CN202210800919 A CN 202210800919A CN 115232163 B CN115232163 B CN 115232163B
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halogen
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CN115232163A (en
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陈兴宽
欧文漂
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Jinan University
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    • 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
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C07F7/0816—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring comprising Si as a ring atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • 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
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
    • C07F7/0832—Other preparations
    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a silicon center chiral molecular compound and a preparation method and application thereof. The preparation method of the silicon center chiral molecular compound does not need to use transition metal as a catalyst, can perform reaction under milder conditions, has the advantages of environmental protection, low cost, wide substrate selectivity and mild reaction conditions, and has higher yield and selectivity of the obtained product; the prepared product has two chiral centers of carbon and silicon, is novel in structure, can be converted into a chiral ligand containing silicon, a chiral medicament containing silicon, an organic photoelectric functional material and the like by a simple method, and has a good application prospect.

Description

Silicon center chiral molecular compound and preparation method and application thereof
Technical Field
The invention belongs to the technical field of organic synthesis. More particularly, relates to a silicon center chiral molecule compound, a preparation method and application thereof.
Background
Silicon is the second most abundant element present in the earth's environment, with the next level of oxygen. In the field of element organic chemistry, organic silicon is one of the fastest growing technologies, and particularly, organic silicon materials are widely applied, so that research on all directions of organic silicon is greatly promoted. For example, the silicon center chiral molecular compound is a unique chiral element organic compound, has been applied to various fields of synthetic chemistry, material chemistry, pharmaceutical chemistry, life science and the like at present, and shows some special properties, and is expected to be applied to the related polymer fields including stereoregular polymer synthesis.
However, in practice, the silicon element exists substantially in the form of an inorganic silicon compound, and there is no organic silicon compound (containing Si-C bond) in the true sense in nature. Because silicon atoms have large radius and certain coordination capability, and are combined with oxygen atoms to form stable compounds, conventional reactions such as oxidation, addition and substitution are difficult to occur, and direct construction of a silicon chiral center is difficult, the silicon center chiral molecule compound is a challenging problem in both organic silicon chemistry and organic synthesis chemistry. Organic catalytic synthesis of chiral molecules in silicon centers has been reported only rarely, for example, chinese patent application discloses a chiral compound in silicon centers and a synthesis method thereof, the synthesis method uses aza-aryl tertiary butyl diphenyl silane as a raw material to react with olefin, uses a complex compound formed by palladium salt and ligand as a catalyst, and needs to add a reaction auxiliary agent and an oxidant, and the chiral compound in silicon centers can be obtained by reaction in a reaction medium at 60-100 ℃, so that the reaction is complicated, more reagents are needed, the cost is high, and the yield and the selectivity still have room for improvement.
Disclosure of Invention
The invention aims to overcome the defects of multiple reagents, high cost, complicated steps, high condition requirements and limited yield and selectivity of the existing preparation method of the silicon center chiral molecular compound, and provides the preparation method of the silicon center chiral molecular compound, which is environment-friendly, low in cost, mild in reaction condition, simple in reaction and high in yield and selectivity.
The invention aims to provide a silicon center chiral molecule compound.
It is another object of the present invention to provide the use of the silicon-centered chiral molecular compound.
The above object of the present invention is achieved by the following technical scheme:
a preparation method of a silicon center chiral molecule compound comprises the following synthetic routes:
wherein R is 1 Selected from C 1～12 Alkyl, C 2～12 Alkenyl, C 2～12 Alkynyl, aryl or substituted aryl, halogen, C 1～10 One of the halogenated alkyl groups, the substituent in the substituted aryl group being selected from C 1～5 Alkoxy, C 1～3 Haloalkyl, halogen, C 1～10 An alkyl group; r is R 2 Is C 1～12 Alkyl, C 2～12 Alkenyl, C 2～12 Alkynyl; r is R 3 Selected from hydrogen, C 1～6 Alkyl, C 1～5 Alkoxy, halogen, C 1～3 One of the haloalkyl groups;
the preparation method comprises the following steps:
the compound 1, the catalyst NHC and an alkaline reagent are reacted completely in an organic solution at 20-35 ℃ under the protection of inert gas, and the mixture is separated and purified to obtain the catalyst;
wherein the catalyst NHC is selected from any one of the following structures:
the invention adopts N-heterocyclic carbene (NHC) as a catalyst to perform the intramolecular benzoin reaction of diaryl aldehyde with silicon-containing prochiral center, and the reaction mechanism is as follows:
specifically, chiral NHC catalysts first chemically selectively attack the favored carbonyl carbon to produce Breslow intermediate I; then forming an intermediate II through intramolecular nucleophilic addition (benzoin reaction) with another formyl group; finally, intermediate II generates a silicon ring with a carbon and silicon stereocenter as the target product by intramolecular proton transfer, while NHC catalyst release continues for catalytic cycling.
Further, the mol ratio of the compound 1 to the catalyst NHC to the alkaline reagent is 1 (0.05-0.3) to 0.3-2.
Further, the reaction time is 12 to 48 hours.
Further, the inert gas is nitrogen or argon.
In addition, the invention also claims a silicon center chiral molecule compound which has the structure shown in a compound 2:
wherein R is 1 Selected from C 1～12 Alkyl, C 2～12 Alkenyl, C 2～12 Alkynyl groupAryl or substituted aryl, halogen, C 1～10 One of the halogenated alkyl groups, the substituent in the substituted aryl group being selected from C 1～5 Alkoxy, C 1～3 Haloalkyl, halogen, C 1～10 An alkyl group; r is R 2 Is C 1～12 Alkyl, C 2～12 Alkenyl, C 2～12 Alkynyl; r is R 3 Selected from hydrogen, C 1～6 Alkyl, C 1～5 Alkoxy, halogen, C 1～3 One of the haloalkyl groups.
Preferably, R 1 Selected from C 1～6 An alkyl, vinyl, aryl or one of substituted aryl and haloalkyl, wherein the substituent in the substituted aryl is selected from methoxy, trifluoromethyl, halogen and methyl; r is R 2 Is C 1～7 Alkyl, C 2～8 Alkenyl, phenylethynyl; r is R 3 One selected from hydrogen, methoxy, trifluoromethyl, halogen and methyl.
More preferably, the R 1 One of n-hexyl, vinyl, phenyl or substituted phenyl, naphthyl and chloromethane, wherein the substituent in the substituted phenyl is selected from methoxy, trifluoromethyl, halogen and methyl; r is R 2 Methyl, ethyl, n-butyl, isobutyl, isopropyl, cyclopropyl, vinyl, styryl, phenylethynyl; r is R 3 One selected from hydrogen, methyl, methoxy, trifluoromethyl and halogen.
In addition, the silicon center chiral molecular compound can generate chiral o-diol, triarylmethylsilane or meso-diol compound containing chiral silicon through simple conversion, and the compound 2a can be converted into the following various compounds:
therefore, the invention also claims the application of the silicon center chiral molecular compound in preparing silicon-containing chiral ligands, silicon-containing chiral drugs and organic photoelectric functional materials.
The invention has the following beneficial effects:
the invention provides a preparation method of a silicon center chiral molecular compound, which does not need to use transition metal as a catalyst, can perform reaction under milder conditions, has the advantages of environmental protection, low cost, wide substrate selectivity and mild reaction conditions, and has higher yield and selectivity of the obtained product; the prepared product has two chiral centers of carbon and silicon, is novel in structure, can be converted into a chiral ligand containing silicon, a chiral medicament containing silicon, an organic photoelectric functional material and the like by a simple method, and has a good application prospect.
Drawings
FIG. 1 is an H spectrum of a silicon center chiral molecule compound 2a prepared in example 1 of the present invention.
FIG. 2 is a graph showing the C-profile of a silicon-centered chiral molecular compound 2a prepared in example 1 of the present invention.
FIG. 3 is a HPLC chart of a silicon center chiral molecule compound 2a prepared in example 1 of the present invention.
Detailed Description
The invention is further illustrated in the following drawings and specific examples, which are not intended to limit the invention in any way. Unless specifically stated otherwise, the reagents, methods and apparatus employed in the present invention are those conventional in the art.
Reagents and materials used in the following examples are commercially available unless otherwise specified.
The catalyst structure adopted in the embodiment of the invention is any one of the following:
EXAMPLE 1 preparation of silicon-centered chiral molecular Compound 2a and conditions are preferably
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
chiral catalyst NHC (20 mol%), silicon-containing diaryl aldehyde 1a (1.3221 g,4 mmol) and alkaline reagent (100 mol%) were placed in a 120mL dry Schlenk tube equipped with a magnetic stirring bar, sealed with a septum, evacuated and refilled with nitrogen (3 cycles); solvent (0.1M) was added and the reaction mixture was stirred at 25 ℃ (oil bath temperature) for 48 hours; after complete consumption of 1a (monitored by TLC), the reaction mixture was concentrated under reduced pressure, the residue was subjected to column chromatography on silica gel, and chromatographed using petroleum ether/EtOAc (v/v) =20/1 as eluent to give the silicon-centered chiral molecular compound 2a.
The hydrogen spectrum of compound 2a was determined (see in particular fig. 1). Chemical shift 1H NMR (400 mhz, cdcl 3) delta 8.28 (d, j=7.6 hz, 1H), 7.91 (d, j=6.8 hz, 1H), 7.72 (t, j=8.4 hz, 2H), 7.66 (t, j=8.8 hz, 1H), 7.58 (t, j=8.0 hz, 1H), 7.52 (t, j=7.6 hz, 1H), 7.42 (d, j=8.0 hz, 2H), 7.35 (t, j=6.4 hz, 2H), 7.29 (t, j=7.2 hz, 2H), 6.06 (d, j=6.4 hz, 1H), 4.48 (d, j=6.8 hz, 1H), 0.93 (s, 3H) of the hydrogen spectrum peak of compound 2a can be seen from the figure;
the carbon spectrum of compound 2a was determined (see in particular fig. 2). From the figure, it can be seen that the chemical shift 13C {1H } NMR (100 MHz, CDCl 3) of the carbon spectrum peak of compound 2a, delta 198.6,144.3,139.5,138.0,135.4,134.9,134.3,134.0,132.5,131.7,131.1,131.0,130.2,130.0,128.4,127.2,124.1,76.6, -2.5.
HRMS(ESI-TOF)m/z:[M+H] + calcd.for C 21 H 19 O 2 Si + 331.1149,found 331.1142.[α] 21 D＝+8.9(c＝1.0in CH 2 Cl 2 )。
Measuring the HPLC spectrum of the compound 2a (see in particular FIG. 3), and carrying out high performance liquid chromatography on racemate and chiral products of the compound 2a from top to bottom; the stereoselectivity of the compound was found to be 97% ee [ chiral column IA; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 20.1 min (secondary), 21.8 min (primary) ].
The conversion, dr, ee% measured under different reaction conditions (including catalyst, solvent and base) are shown in table 1.
TABLE 1 Condition optimization of preparation of silicon center chiral molecular Compound 2a
Note that: the conversion rate is measured by a nuclear magnetic internal standard method, the separation yield is measured in brackets, the dr value is measured by nuclear magnetic rough spectrum, and the ee value is measured by high performance liquid chromatography. DIPEA is N, N-diisopropylethylamine, DBU is 1, 8-diazabicyclo undec-7-ene, DMAP is 4-dimethylaminopyridine, DABCO is 1, 4-diazabicyclo [ 2.2.2 ] octane, THF is tetrahydrofuran, etOAc is ethyl acetate.
As can be seen from the table, when the adopted alkaline reagent is N, N-diisopropylethylamine, 1, 8-diazabicyclo undec-7-ene, 4-dimethylaminopyridine, cesium carbonate, sodium bicarbonate and sodium acetate, the conversion rate is higher and the selectivity is better; the solvent can be selected from dichloromethane, chloroform, toluene, tetrahydrofuran, ethyl acetate, and acetonitrile.
EXAMPLE 2 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
chiral catalyst NHC G (204.2 mg,0.4 mmol), silicon-containing diaryl aldehyde 1a (1.3221G, 4 mmol) and NaOAc (328.1 mg,4 mmol) were placed in a 120mL dry Schlenk tube equipped with a magnetic stir bar, sealed with a septum, evacuated and refilled with nitrogen (3 cycles); etOAc (40 mL) was added and the reaction mixture was stirred at 25 ℃ (oil bath temperature) for 96 hours; after complete consumption of 1a (monitored by TLC), the reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel with petroleum ether/EtOAc (v/v) =20/1 as eluent to give silicon-centered chiral molecular compound 2a (1.2125 g,3.67mmol, yield: 91%, dr >30:1, ee: 97%).
EXAMPLE 3 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 2, this example uses NHC A as catalyst, DIPEA as alkaline agent, and dichloromethane as solvent, and other conditions and parameters refer to example 2, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 71%, and a dr value of 1: the ee value was 83%.
EXAMPLE 4 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 3, this example uses NHC B as catalyst, DIPEA as alkaline agent, and dichloromethane as solvent, and other conditions and parameters refer to example 3, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 100%, and a dr value of 6: the ee value was 95%.
EXAMPLE 5 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 3, this example uses NHC G as catalyst, DIPEA as alkaline agent, and dichloromethane as solvent, and other conditions and parameters refer to example 3, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 100%, and a dr value of 13: the ee value was 78%.
EXAMPLE 6 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 5, this example uses NHC G as catalyst, DABCO as alkaline agent, and dichloromethane as solvent, and other conditions and parameters refer to example 5, and the reaction is performed for 48 hours at 25 ℃, so as to obtain a silicon center chiral molecular compound 2a with a yield of 38%, and a dr value of 11: the ee value was 80%.
EXAMPLE 7 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 5, this example uses NHC G as catalyst, cesium carbonate as alkaline agent, and methylene chloride as solvent, and other conditions and parameters refer to example 5, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 88%, and a dr value of 10: the ee value was 58%.
EXAMPLE 8 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 5, this example uses NHC G as catalyst, sodium bicarbonate as alkaline agent, and dichloromethane as solvent, and other conditions and parameters refer to example 5, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 100%, and a dr value of 21: the ee value was 94%.
EXAMPLE 9 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 5, this example uses NHC G as catalyst, sodium acetate as alkaline agent, and dichloromethane as solvent, and other conditions and parameters refer to example 5, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 100%, and a dr value of 26: the ee value was 96%.
EXAMPLE 10 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 9, this example uses NHC G as catalyst, sodium acetate as alkaline agent, toluene as solvent, and other conditions and parameters refer to example 9, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 100%, and a dr value of 18: the ee value was 93%.
EXAMPLE 11 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 9, this example uses NHC G as a catalyst, sodium acetate as an alkaline reagent, tetrahydrofuran as a solvent, and other conditions and parameters refer to example 9, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 100%, and a dr value of 20: the ee value was 97%.
EXAMPLE 12 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 9, this example uses NHC G as catalyst, sodium acetate as alkaline agent, acetonitrile as solvent, and other conditions and parameters refer to example 9, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon center chiral molecular compound 2a with a yield of 92%, and a dr value of >30: the ee value was 92%.
EXAMPLE 13 preparation method of silicon center chiral molecular Compound 2a
The preparation method of the silicon center chiral molecule compound 2a comprises the following steps:
unlike example 9, this example uses NHC G as catalyst, sodium acetate as alkaline agent, ethyl acetate as solvent, and other conditions and parameters refer to example 9, and the reaction is performed for 48 hours at 25 ℃ to obtain a silicon-centered chiral molecular compound 2a with a yield of 100%, and a dr value of >30: the ee value was 97%.
EXAMPLE 14 preparation of silicon-centered chiral molecular Compounds 2 b-2 aa
The conditions and methods of reference examples 1 to 23 gave compounds 2b to 2aa:
wherein the structure of the compound is characterized by:
compound 2b:1H NMR (400 MHz, CDCl) 3 )δ8.27(d,J＝7.6Hz,1H),7.90(d,J＝7.6Hz,1H),7.74-7.69(m,2H),7.65(t,J＝7.2Hz,1H),7.57(t,J＝8.0Hz,1H),7.51(t,J＝7.2Hz,1H),7.36-7.33(m,3H),6.84(d,J＝8.4Hz,2H),6.09(d,J＝6.8Hz,1H),4.48(d,J＝6.8Hz,1H),3.76(s,3H),0.91(s,3H)；13C{1H}NMR(100MHz,CDCl3)δ198.6,161.2,144.3,139.5,138.5,135.8,135.3,133.9,132.5,132.1,131.0,130.9,30.1,127.2,125.4,124.1,114.2,76.6,55.0,-2.3.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C 22 H 21 O 3 Si + 361.1254,found 361.1251.[α] 21 D＝-4.2(c＝1.0in CH 2 Cl 2 ).
HPLC analysis 96% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 36.5 min (minor peak), 21.8 min (major peak) ].
Compound 2c:1H NMR (400 MHz, CDCl) 3 )δ8.29(d,J＝8.0Hz,1H),7.91(d,J＝7.6Hz,1H),7.76-7.68(m,3H),7.62(t,J＝7.6Hz,1H),7.57-7.53(m,5H),7.38(t,J＝7.2Hz,1H),5.92(d,J＝6.4Hz,1H),4.46(d,J＝6.4Hz,1H),0.94(s,3H)；13C{1H}NMR(100MHz,CDCl3)δ198.3,144.2,140.3,139.6,136.8,135.4,134.5,134.1,132.7,131.9(q,JC-F＝32.2Hz),131.3(d,JC-F＝35.6Hz),130.7,130.6,127.6,124.9(q,JC-F＝3.5Hz),124.4,123.8(q,JC-F＝270.6Hz),76.7,-2.8.
HRMS(ESI-TOF)m/z:[M+H] + calcd.for C 22 H 18 F 3 O 2 Si + 399.1023,found 399.1019.[α] 21 D＝+7.5(c＝1.0in CH 2 Cl 2 ).
HPLC analysis 96% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 13.3 min (minor peak), 14.6 min (major peak) ].
Compound 2d:1H NMR (400 mhz, cdcl 3) delta 8.28 (d, j=8.0 hz, 1H), 7.90 (d, j=7.2 hz, 1H), 7.75-7.65 (m, 3H), 7.59 (t, j=7.6 hz, 1H), 7.53 (t, j=7.6 hz, 1H), 7.42-7.34 (m, 3H), 6.98 (t, j=9.2 hz, 2H), 6.00 (d, j=6.8 hz, 1H), 4.47 (d, j=6.4 hz, 1H), 0.92 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.4,164.2 (d, JC-F=248.5 Hz), 144.3,139.5,137.7,136.3 (d, JC-F=7.7 Hz), 135.3,134.0,132.6,131.4,131.3,131.1,130.5 (d, JC-F=3.8 Hz), 130.4,127.3,124.3,115.7 (d, JC-F=19.9 Hz), 76.6, -2.4.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C21H18FO2Si+349.1055,found349.1055.[α]21D＝+9.5(c＝1.0in CH2Cl2).
HPLC analysis 91% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 17.0 min (minor peak), 19.1 min (major peak) ].
Compound 2e:1H NMR (400 mhz, cdcl 3) delta 8.28 (d, j=8.0 hz, 1H), 7.89 (d, j=7.6 hz, 1H), 7.75-7.65 (m, 3H), 7.59 (t, j=7.6 hz, 1H), 7.53 (t, j=8.0 hz, 1H), 7.38-7.36 (m, 3H), 7.27 (d, j=8.0 hz, 2H), 5.97 (d, j=6.4 hz, 1H), 4.47 (d, j=6.4 hz, 1H), 0.92 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.4,144.3,139.5,137.4,136.5,135.6,135.3,134.0,133.4,132.6,131.3,131.2,131.1,130.4,128.7,127.3,124.3,76.6, -2.6.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C21H18ClO2Si+365.0759,found365.0759.[α]20D＝-1.1(c＝1.0in CH2Cl2).
HPLC analysis 95% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 17.0 min (minor peak), 19.2 min (major peak) ].
Compound 2f:1H NMR (400 mhz, cdcl 3) delta 8.27 (d, j=8.0 hz, 1H), 7.90 (d, j=7.6 hz, 1H), 7.72 (t, j=8.8 hz, 2H), 7.65 (t, j=7.2 hz, 1H), 7.57 (t, j=7.6 hz, 1H), 7.51 (t, j=7.6 hz, 1H), 7.36-7.31 (m, 3H), 7.11 (d, j=7.6 hz, 2H), 6.08 (d, j=6.8 hz, 1H), 4.48 (d, j=6.8 hz, 1H), 2.30 (s, 3H), 0.91 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.6,144.3,140.1,139.5,138.4,135.4,134.3,133.9,132.5,132.0,131.1,131.0,130.9,130.1,129.2,127.2,124.1,76.6,21.5, -2.5.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C22H21O2Si+345.1305,found 345.1301.[α]21D＝-0.4(c＝1.0in CH2Cl2).
HPLC analysis 97% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 18.2 min (minor peak), 22.6 min (major peak) ].
Compound 2g:1H NMR (400 mhz, cdcl 3) delta 8.28 (d, j=8.4 hz, 1H), 7.90 (d, j=6.8 hz, 1H), 7.72 (t, j=8.0 hz, 2H), 7.66 (t, j=7.2 hz, 1H), 7.57 (t, j=8.0 hz, 1H), 7.51 (t, j=7.6 hz, 1H), 7.35 (t, j=6.8 hz, 1H), 7.33-7.17 (m, 4H), 6.08 (d, j=6.8 hz, 1H), 4.50 (d, j=6.4 hz, 1H), 2.25 (s, 3H), 0.91 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.5,144.3,139.4,138.2,137.8,135.4,134.7,134.7,133.9,132.5,131.9,131.4,131.1,131.0,130.9,130.2,128.3,127.2,124.1,76.6,21.4, -2.5.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C22H21O2Si+345.1305,found345.1299.[α]21D＝+6.6(c＝1.0in CH2Cl2).
HPLC analysis 97% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 17.4 min (minor peak), 19.2 min (major peak) ].
Compound 2h:1H NMR (400 mhz, cdcl 3) delta 8.34 (d, j=8.0 hz, 1H), 7.85 (d, j=7.2 hz, 1H), 7.72 (d, j=7.2 hz, 1H), 7.69-7.62 (m, 2H), 7.58 (t, j=7.6 hz, 1H), 7.46 (t, j=7.6 hz, 1H), 7.32 (t, j=7.6 hz, 1H), 7.26 (t, j=7.6 hz, 1H), 7.20 (d, j=7.6 hz, 1H), 7.11 (d, j=7.6 hz, 1H), 7.04 (t, j=7.6 hz, 1H), 6.12 (d, j=6.0 hz, 1H), 4.57 (d, j=6.0 hz, 1H), 2.25 (s, 3H), 1.00 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.1,144.3,144.1,139.5,138.9,135.8,135.6,133.7,133.4,133.1,132.6,131.2,130.7,130.5,130.4,130.1,127.3,125.5,124.1,76.7,23.3, -3.4.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C22H21O2Si+345.1305,found345.1302.[α]21D＝-5.7(c＝1.0in CH2Cl2).
HPLC analysis 90% ee, [ chiral IC column; the flow rate was 1.0 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 7.0 min (minor peak), 13.7 min (major peak) ].
Compound 2i:1H NMR (400 MHz, CDCl 3) delta 8.39 (d, J=8.0 Hz, 1H), 8.00 (d, J=8.4 Hz, 1H), 7.93 (t, J=8.4 Hz, 2H), 7.87-7.82 (m, 2H), 7.70-7.60 (m, 3H), 7.50-7.46 (m, 2H), 7.44-7.39 (m, 2H), 7.34-7.30 (m, 2H), 6.24 (d, J=6.0 Hz, 1H), 4.53 (d, J=6.0 Hz, 1H), 1.09 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.0,144.4,139.3,138.9,137.0,135.6,133.7,133.6,133.5,132.9,132.8,131.3,131.1,130.9,130.3,129.1,127.9,127.6,126.2,125.7,125.3,124.3,76.7, -2.8.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C25H21O2Si+381.1305,found381.1302.[α]21D＝+34.0(c＝1.0in CH2Cl2).
HPLC analysis 88% ee, [ chiral IC column; the flow rate was 1.0 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 8.9 min (minor peak), 13.3 min (major peak) ].
Compound 2j:1H NMR (400 mhz, cdcl 3) delta 8.31 (d, j=7.6 hz, 1H), 7.98 (d, j=7.2 hz, 1H), 7.91 (s, 1H), 7.78-7.69 (m, 6H), 7.61 (t, j=8.0 hz, 1H), 7.54 (t, j=7.6 hz, 1H), 7.48-7.37 (m, 4H), 6.11 (d, j=6.4 hz, 1H), 4.45 (d, j=6.4 hz, 1H), 0.98 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.5,144.4,139.6,138.0,135.5,135.4,134.1,133.0,132.6,132.3,131.8,131.2,131.1,130.3,129.8,128.1,127.8,127.7,127.3,126.9,126.2,124.2,76.7, -2.5.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C25H21O2Si+381.1305,found381.1297.[α]21D＝-14.5(c＝1.0in CH2Cl2).
HPLC analysis 95% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 23.1 min (minor peak), 25.9 min (major peak) ].
Compound 2k:1H NMR (400 MHz, CDCl 3) delta 8.26 (d, J=8.0 Hz, 1H), 7.93 (d, J=7.6 Hz, 1H), 7.75 (t, J=7.2 Hz, 2H), 7.68 (t, J=7.6 Hz, 1H), 7.58 (t, J=8.0 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 7.41-7.33 (m, 4H), 7.28 (t, J=7.2 Hz, 2H), 5.99 (d, J=6.8 Hz, 1H), 4.40 (d, J=6.8 Hz, 1H), 1.54-1.41 (m, 2H), 1.07 (t, J=8.0 Hz, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.9,144.8,140.3,136.6,135.5,134.5,134.2,134.1,132.3,131.1,131.0,130.3,130.2,130.0,128.3,127.2,124.3,76.6,7.8,5.1.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C22H21O2Si+345.1305,found345.1303.[α]21D＝+8.4(c＝1.0inCH2Cl2).
HPLC analysis 93% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 18.4 min (minor peak), 20.3 min (major peak) ].
Compound 2l:1H NMR (400 MHz, CDCl 3) delta 8.25 (d, J=8.0 Hz, 1H), 7.93 (d, J=7.2 Hz, 1H), 7.76-7.66 (m, 3H), 7.61-7.51 (m, 2H), 7.45-7.33 (m, 4H), 7.28 (t, J=7.6 Hz, 2H), 5.99 (d, J=6.8 Hz, 1H), 4.39 (d, J=6.8 Hz, 1H), 1.49-1.34 (m, 6H), 0.90 (t, J=6.4 Hz, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.9,144.8,140.3,136.9,136.1,135.5,134.4,134.3,134.2,132.3,131.1,130.6,130.1,129.9,128.3,127.2,124.3,76.6,26.6,26.0,13.6,13.0.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C24H25O2Si+373.1618,found373.1615.[α]21D＝+10.3(c＝1.0in CH2Cl2).
HPLC analysis 96% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 14.5 min (minor peak), 16.5 min (major peak) ].
Compound 2m:1H NMR (400 MHz, CDCl 3) delta 8.25 (d, J=8.0 Hz, 1H), 7.92 (d, J=7.2 Hz, 1H), 7.76-7.65 (m, 3H), 7.59-7.50 (m, 2H), 7.41-7.33 (m, 4H), 7.29-7.24 (m, 2H), 5.99 (d, J=6.8 Hz, 1H), 4.40 (d, J=6.8 Hz, 1H), 1.49-1.22 (m, 12H), 0.87 (t, J=6.4 Hz, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.9,144.7,140.3,136.9,136.1,135.5,134.4,134.3,134.2,132.3,131.0,130.6,130.1,129.9,128.3,127.2,124.3,76.5,33.6,31.7,28.7,23.8,22.6,14.1,13.3.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C27H31O2Si+415.2088,found415.2083.[α]21D＝+12.4(c＝1.0in CH2Cl2).
HPLC analysis 91% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 13.2 min (minor peak), 14.5 min (major peak) ].
Compound 2n:1H NMR (400 mhz, cdcl 3) delta 8.19 (d, j=8.0 hz, 1H), 7.98 (d, j=7.2 hz, 1H), 7.79-7.75 (m, 2H), 7.66 (t, j=7.6 hz, 1H), 7.59-7.51 (m, 2H), 7.42-7.32 (m, 4H), 7.27 (t, j=7.6 hz, 2H), 5.94 (d, j=6.8 hz, 1H), 4.29 (d, j=7.2 hz, 1H), 2.07-1.97 (m, 1H), 1.54-1.42 (m, 2H), 0.86 (d, j=6.4 hz, 3H), 0.83 (d, j=6.4 hz, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 199.3,144.6,140.4,137.5,136.0,134.7,134.6,134.5,131.9,131.2,131.0,130.8,130.0,129.9,128.3,127.0,124.2,76.7,26.5,26.3,24.8,23.1.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C24H25O2Si+373.1618,found373.1615.[α]21D＝+12.6(c＝1.0in CH2Cl2).
HPLC analysis 85% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 15.4 min (minor peak), 19.1 min (major peak) ].
Compound 2o:1H NMR (400 MHz, CDCl 3) major diastereomer: delta 8.12 (d, J=7.6 Hz, 1H), 7.83-7.75 (m, 2H, overlapped), 7.52-7.33 (m, 7H, overlapped), 7.28 (t, J=7.6 Hz,1H, overlapped), 7.11 (t, J=7.2 Hz, 1H), 7.01 (d, J=7.6 Hz, 1H), 6.23 (d, J=7.6 Hz, 1H), 4.38-4.34 (m, 1H, overlapped), 1.99-1.90 (m, 1H, overlapped), 1.32-1.25 (m, 6H, overlapped); 13C {1H } NMR (100 MHz, CDCl 3) delta 200.0,144.3,141.5,137.9,136.7,136.3,134.6,134.4,132.1,131.5,130.7,130.0,129.8,129.7,128.0,126.9,123.5,77.1,19.2,18.5,13.0; minor diastereomer δ8.25 (d, j=8.0 hz,1 h), 7.99 (d, j=7.2 hz,1 h), 7.83-7.75 (m, 1h, overlapped), 7.67 (t, j=7.2 hz,1 h), 7.58 (t, j=7.6 hz,1 h), 7.52-7.33 (m, 7h, overlapped), 7.28 (t, j=7.6 hz,1h, overlapped), 5.96 (d, j=8.0 hz,1 h), 4.38-4.34 (m, 1h, overlapped), 1.99-1.90 (m, 1h, overlapped), 1.32-1.25 (m, 6h, overlapped); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.8,145.0,140.5,137.8,136.6,135.3,134.3,134.0,131.4,131.3,131.0,130.1,130.1,129.9,128.2,127.0,124.5,76.4,18.1,17.7,12.8.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C23H23O2Si+359.1462,found359.1458.[α]19D＝+26.6(c＝1.0in CH2Cl2).
HPLC analysis of 82% ee,70% ee [ chiral ASH column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 12.7 min (minor peak), 19.7min (major peak); 15.0 minutes (minor peak), 15.8 minutes (major peak) ].
Compound 2p:1H NMR (400 MHz, CDCl 3) delta 8.38 (d, J=7.2 Hz, 1H), 8.30 (d, J=7.6 Hz, 1H), 8.08 (d, J=7.2 Hz, 1H), 7.74-7.67 (m, 2H), 7.60-7.50 (m, 2H), 7.39-7.33 (m, 2H), 7.30-7.23 (m, 4H), 5.92 (d, J=6.4 Hz, 1H), 4.52 (d, J=6.4 Hz, 1H), 0.98-0.96 (m, 2H), 0.37-0.34 (m, 2H), 0.21-0.13 (m, 1H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.4,144.3,139.2,138.6,136.2,135.2,134.9,132.4,131.9,131.0,130.3,130.2,130.1,128.1,127.1,124.1,76.6,1.6,0.8, -7.8.
HRMS(ESI-TOF)m/z:[M+H]+calcd.For C23H21O2Si+357.1305,found357.1297.[α]21D＝+39.3(c＝1.0in CH2Cl2).
HPLC analysis 94% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 14.0 min (minor peak), 16.1 min (major peak) ].
Compound 2q:1H NMR (400 MHz, CDCl 3) delta 8.28 (d, J=8.0 Hz, 1H), 7.90 (d, J=7.2 Hz, 1H), 7.74 (d, J=8.0 Hz, 1H), 7.69-7.62 (m, 2H), 7.59-7.50 (m, 2H), 7.44-7.38 (m, 3H), 7.35-7.30 (m, 3H), 6.58-6.50 (m, 2H), 6.02 (d, J=6.4 Hz, 1H), 5.83-5.74 (m, 1H), 4.49 (d, J=6.4 Hz, 1H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.5,144.4,139.9,139.8,139.7,136.9,136.8,135.4,135.2,133.2,132.4,131.2,131.1,131.0,130.4,130.3,128.3,127.2,124.2,76.7.
HRMS(ESI-TOF)m/z:[M+H]+calcd.For C22H19O2Si+343.1149,found343.1149.[α]21D＝+31.1(c＝1.0in CH2Cl2).
HPLC analysis 96% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 14.5 min (minor peak), 16.1 min (major peak) ].
Compound 2r:1H NMR (400 MHz, CDCl 3) δ8.19 (d, J=8.0 Hz, 1H), 7.73 (t, J=7.6 Hz, 2H), 7.58-7.45 (m, 4H), 7.27 (t, J=7.6 Hz, 1H), 6.22 (d, J=6.8 Hz, 1H), 4.55 (d, J=6.8 Hz, 1H), 1.43-1.11 (m, 10H), 0.83 (t, J=6.4 Hz, 3H), 0.73 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.9,144.0,140.2,139.4,135.0,133.7,133.0,132.2,130.6,130.5,129.6,127.1,123.7,76.7,32.9,31.4,24.4,22.5,15.3,14.0, -4.2.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C21H27O2Si+339.1775,found339.1772.[α]20D＝+1.4(c＝1.0in CH2Cl2).
HPLC analysis 91% ee, [ chiral IC column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 11.4 min (minor peak), 17.7 min (major peak) ].
Compound 2s:1H NMR (400 mhz, cdcl 3) delta 8.17 (d, j=7.6 hz, 1H), 7.83 (d, j=7.2 hz, 1H), 7.76 (d, j=8.0 hz, 1H), 7.64-7.41 (m, 4H), 7.32 (t, j=7.2 hz, 1H), 6.12 (d, j=6.8 hz, 1H), 4.41 (d, j=6.8 hz, 1H), 3.28 (dd, J1=14.4 hz, j2=19.6 hz, 2H), 0.89 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.7,144.2,139.9,136.0,135.9,134.5,132.3,131.6,130.6,130.5,129.6,127.5,124.1,76.7,28.8, -5.2.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C16H16ClO2Si+303.0603,found303.0594.[α]20D＝+7.4(c＝0.5in CH2Cl2).
HPLC analysis 86% ee, [ chiral IC column; the flow rate was 1.0 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 8.0 min (minor peak), 12.7 min (major peak) ].
Compound 2t:1H NMR (400 MHz, CDCl 3) major diastereomer: delta 8.23 (d, J=8.0 Hz, 1H), 7.76-7.69 (m, 2H, overlapped), 7.61-7.45 (m, 4H, overlapped), 7.32-7.23 (m, 1H, overlapped), 6.44-6.38 (m, 1H, overlapped), 6.36-6.34 (m, 1H, overlapped), 6.12 (dd, J1=3.2 Hz, J2=14.4 Hz, 1H), 5.76 (dd, J1=3.2 Hz, J2=20.0 Hz, 1H), 4.54-4.50 (m, 1H, overlapped), 0.82 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.7,144.4,139.5,138.3,135.7,135.0,134.7,133.7,132.4,131.7,131.0,130.7,120.0,127.2,123.9,76.6, -3.8; minor diastereomer δ8.18 (d, j=7.6hz, 1H), 7.76-7.69 (m, 2H, overlapped), 7.61-7.45 (m, 4H, overlapped), 7.32-7.23 (m, 1H, overlapped), 6.51 (dd, j1=3.6hz, j2=14.4hz, 1H), 6.36-6.34 (m, 1H, overlapped), 6.22-6.16 (m, 2H), 4.54-4.50 (m, 1H, overlapped), 0.75 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.9,144.0,139.6,139.2,136.9,135.9,134.8,134.6,132.6,132.3,130.8,130.4,129.8,127.1,123.9,76.9, -4.1.
HRMS(ESI-TOF)m/z:[M+H]+calcd.For C17H17O2Si+281.0992,found281.0987.[α]21D＝+14.4(c＝1.0in CH2Cl2).
HPLC analysis 91% ee;88% ee, [ chiral IC column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 13.9 min (minor peak), 24.1 min (major peak); 14.7 minutes (minor peak), 23.1 minutes (major peak) ].
Compound 2u:1H NMR (400 mhz, cdcl 3) delta 8.19 (d, j=8.0 hz, 1H), 7.67 (s, 1H), 7.61 (d, j=8.0 hz, 1H), 7.50 (s, 1H), 7.43 (d, j=6.8 hz, 2H), 7.38-7.27 (m, 5H), 5.99 (d, j=6.4 hz, 1H), 4.51 (d, j=6.4 hz, 1H), 2.48 (s, 3H), 2.38 (s, 3H), 0.92 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.2,143.1,141.5,138.1,137.0,136.6,136.0,135.2,134.6,134.3,131.7,131.6,131.2,131.0,129.9,128.3,124.1,76.3,21.8,21.2, -2.5.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C23H23O2Si+359.1462,found359.1457.[α]21D＝-15.7(c＝1.0in CH2Cl2).
HPLC analysis 97% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 19.5 min (minor peak), 24.6 min (major peak) ].
Compound 2v:1H NMR (400 mhz, cdcl 3) delta 8.31 (d, j=8.8 hz, 1H), 7.65 (d, j=8.8 hz, 1H), 7.44 (d, j=8.0 hz, 2H), 7.38-7.34 (m, 2H), 7.29 (t, j=7.6 hz, 2H), 7.24 (d, j=2.8 hz, 1H), 7.05-6.99 (m, 2H), 5.94 (d, j=6.0 hz, 1H), 4.58 (d, j=6.0 hz, 1H), 3.92 (s, 3H), 3.83 (s, 3H), 0.90 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 197.1,162.4,158.5,140.2,136.5,134.7,134.2,134.1,133.0,132.1,130.0,128.4,125.6,121.7,120.5,115.1,114.2,75.7,55.4,55.3, -2.5.
HRMS(ESI-TOF)m/z:[M+H]+calcd.For C23H23O4Si+391.1360,found391.1356.[α]21D＝-40.3(c＝1.0in CH2Cl2).
HPLC analysis 92% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 22.7 min (minor peak), 30.9 min (major peak) ].
Compound 2w:1H NMR (400 mhz, cdcl 3) delta 8.42 (d, j=8.4 hz, 1H), 8.14 (s, 1H), 7.94 (s, 1H), 7.88 (t, j=8.8 hz, 2H), 7.80 (d, j=8.0 hz, 1H), 7.44-7.32 (m, 5H), 6.14 (d, j=6.0 hz, 1H), 4.48 (d, j=6.4 hz, 1H), 1.05 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 196.9,147.7,141.8,138.7,134.2,134.0 (q, JC-F=32.6 Hz), 132.6 (d, JC-F=21.3 Hz), 131.9 (q, JC-F=3.1 Hz), 131.2 (d, JC-F=91.1 Hz), 130.5 (q, JC-F=3.1 Hz), 129.9 (q, JC-F=32.1 Hz), 128.8,128.3 (q, JC-F=3.6 Hz), 127.3 (q, JC-F=3.2 Hz), 125.1 (d, JC-F=54.1 Hz), 124.9,122.4 (d, JC-F=55.0 Hz), 76.7, -2.8.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C23H17F6O2Si+467.0897,found467.0897.[α]21D＝-2.6(c＝1.0in CH2Cl2).
HPLC analysis 98% ee, [ chiral IB column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 9.6 min (minor peak), 10.4 min (major peak) ].
Compound 2x:1H NMR (400 MHz, CDCl 3) delta 8.37-8.33 (m, 1H), 7.73-7.70 (m, 1H), 7.56-7.54 (m, 1H), 7.42-7.38 (m, 4H), 7.34-7.30 (m, 2H), 7.28-7.23 (m, 1H), 7.21-7.16 (m, 1H), 5.99 (d, J=6.0 Hz, 1H), 4.49 (d, J=6.4 Hz, 1H), 0.93 (s, 3H); 13c {1h } nmr (100 mhz, cdcl 3) δ 196.7,165.0 (d, JC-f=258.3 Hz), 162.0 (d, JC-f=247.6 Hz), 141.3 (d, JC-f=5.5 Hz), 139.7 (d, JC-f=2.5 Hz), 135.5 (d, JC-f=3.0 Hz), 134.5 (d, JC-f=8.8 Hz), 134.1,133.9 (d, JC-f=5.1 Hz), 133.3,130.5,128.6,126.6 (d, JC-f=7.3 Hz), 122.0 (d, JC-f=20.0 Hz), 120.6 (d, JC-f=20.3 Hz), 117.9 (d, JC-f=21.2 Hz), 117.6 (d, JC-f=21.2 Hz), 75.9, -2.7.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C21H17F2O2Si+367.0960,found367.0956.[α]20D＝+2.3(c＝1.0in CH2Cl2).
HPLC analysis 95% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 12.4 min (minor peak), 13.9 min (major peak) ].
Compound 2y:1H NMR (400 MHz, CDCl 3) delta 8.24 (d, J=8.4 Hz, 1H), 7.82 (d, J=2.0 Hz, 1H), 7.68-7.64 (m, 2H), 7.58-7.55 (m, 1H), 7.50-7.47 (m, 1H), 7.41-7.38 (m, 3H), 7.34-7.31 (m, 2H), 5.98 (d, J=6.0 Hz, 1H), 4.47 (d, J=6.4 Hz, 1H), 0.95 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 196.9,142.4,140.0,139.8,137.3,135.1,134.2,133.8,133.7,133.6,133.2,132.9,131.2,130.7,130.5,128.6,126.1,76.1, -2.6.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C21H17Cl2O2Si+399.0369,found399.0367.[α]19D＝-29.1(c＝1.0in CH2Cl2).
HPLC analysis 97% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 12.0 min (minor peak), 13.8 min (major peak) ].
Compound 2z:1H NMR (400 mhz, cdcl 3) delta 7.81 (d, j=8.0 hz, 2H), 7.61 (d, j=8.0 hz, 1H), 7.42 (d, j=6.8 hz, 2H), 7.36-7.26 (m, 4H), 7.22-7.20 (m, 1H), 6.89-6.86 (m, 1H), 6.02 (d, j=6.4 hz, 1H), 4.47 (d, j=6.4 hz, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 0.86 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 198.6,162.2,161.0,146.2,141.2,136.9,135.8,135.5,134.2,129.8,129.6,128.2,122.8,119.5,115.0,113.2,109.7,76.5,55.4,55.2, -2.4.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C23H23O4Si+391.1360,found391.1356.[α]21D＝-30.2(c＝1.0in CH2Cl2).
HPLC analysis 94% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 38.8 min (minor peak), 45.0 min (major peak) ].
Compound 2aa: 1 H NMR(400MHz,CDCl3)δ8.00-7.97(m,1H),7.92-7.88(m,1H),7.70-7.67(m,1H),7.48-7.45(m,1H),7.41-7.36(m,4H),7.32-7.28(m,2H),7.08-7.03(m,1H),6.01(d,J＝6.0Hz,1H),4.45(d,J＝6.0Hz,1H),0.92(s,3H)；13C{1H}NMR(100MHz,CDCl3)δ196.9,166.0(d,JC-F＝131.0Hz),163.5(d,JC-F＝132.2Hz),147.1(d,JC-F＝7.1Hz),141.8(d,JC-F＝6.1Hz),137.6(d,JC-F＝6.8Hz),136.1(d,JC-F＝7.9Hz),134.2,134.1,133.6(d,JC-F＝4.1Hz),130.3,128.5,127.0(d,JC-F＝3.6Hz),119.9(d,JC-F＝19.8Hz),117.9(d,JC-F＝21.7Hz),114.5(d,JC-F＝20.1Hz),112.2(d,JC-F＝22.7Hz),76.2,-2.3.
HRMS(ESI-TOF)m/z:[M+H]+calcd.for C21H17F2O2Si+367.0960,found367.0956.[α]21D＝-14.3(c＝1.0in CH2Cl2).
HPLC analysis 97% ee, [ chiral IA column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=5/95; retention time 17.2 min (minor peak), 18.9 min (major peak) ].
EXAMPLE 15 preparation method of silicon center chiral molecular Compound 3
To a solution of 2a (60.1 mg,0.2mmol,97% ee) in MeOH (2 mL) at zero degrees NaBH was added 4 (11.4 mg,0.3 mmol) and then allowing the reaction mixture to warm to room temperature and stirring overnight; after complete consumption of 2a (monitored by TLC), saturated aqueous ammonium chloride (10 mL) was added, the reaction mixture was extracted with ethyl acetate (10 mL x 3), the combined organic layers were washed with brine and dried over sodium sulfate, the solvent was removed by filtration and reduced pressure to give a residue which was purified by column chromatography using petroleum ether/EtOAc (v/v) =3/1 to 1/1 as eluent to give meso product 3 (50.5 mg,0.151mmol,76% yield,>30:1)。
compound 3:1H NMR (400 mhz, cdcl 3) delta 7.72 (d, j=7.2 hz, 2H), 7.11 (d, j=8.0 hz, 2H), 7.49 (t, j=7.6 hz, 2H), 7.37 (t, j=7.2 hz, 2H), 7.32-7.27 (m, 3H), 7.23 (t, j=6.8 hz, 2H), 5.29 (s, 2H), 2.11 (br, 2H), 0.87 (s, 3H); 13 C{1H}NMR(100MHz,CDCl3)δ146.2,137.2,134.7,134.2,132.3,130.3,129.4,129.1,128.0,127.2,76.7,-2.4.HRMS(ESI-TOF)m/z:[M+Na]+calcd.for C21H20NaO2Si+355.1125,found355.1122.
EXAMPLE 16 preparation method of silicon center chiral molecular Compound 4
To a solution of 2a (60.1 mg,0.2mmol,97% ee) in tetrahydrofuran (2 mL) was added vinyl MgBr (1.0M in THF, 0.8mL,0.8 mmol) or PMPMgBr (1.0M in THF, 0.8mL,0.8 mmol) at zero degrees. The reaction mixture was then allowed to warm to room temperature and stirred overnight. After complete consumption of 2a (TLC monitoring), the reaction was quenched with water (10 mL) and extracted with EtOAc (10 ml×3). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. The solvent was removed by filtration and reduced pressure to give a residue, which was purified by column chromatography using petroleum ether/EtOAc (v/v) =10/1 to 5/1 as eluent to give the desired product 4a (62.3 mg,0.174mmol,87% yield, >30:1,96% ee) or 4b (72.9 mg,0.166mmol,83% yield, >30:1,96% ee).
Compound 4a: 1 H NMR(400MHz,acetone-d6)δ7.79(d,J＝8.4Hz,1H),7.48(d,J＝7.6Hz,2H),7.39-7.30(m,7H),7.11-7.07(m,3H),5.71-5.65(m,1H),5.29(d,J＝17.2Hz,1H),5.17(br,1H),4.84(d,J＝10.4Hz,2H),4.69(br,1H),0.85(s,3H)；13C{1H}NMR(100MHz,acetone-d6)δ150.7,149.6,145.2,140.9,137.0,136.7,136.3,136.1,135.5,130.3,130.2,129.9,129.7,128.6,128.5,127.2,126.2,111.7,87.8,81.8,-0.1.HRMS(ESI-TOF)m/z:[M+Na]+calcd.for C23H22NaO2Si+381.1281,found 381.1279.[α]21D = +62.7 (c=1.0in ch2cl 2.) HPLC analysis 96% ee, [ chiral ID column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 10.1 min (minor peak), 11.4 min (major peak)].
Compound 4b: 1 H NMR(400MHz,acetone-d6)δ7.56(d,J＝5.6Hz,3H),7.42-7.23(m,5H),7.11-6.93(m,6H),6.63(d,J＝8.8Hz,3H),5.34(br,1H),4.98(br,1H),3.66(s,3H),0.92(s,3H)；13C{1H}NMR(100MHz,acetone-d6)δ158.9,152.7,149.6,141.7,138.8,137.2,136.4,132.4,129.8,129.7,129.4,128.5,126.7,126.1,113.2,89.0,83.1,55.2,-0.0.HRMS(ESI-TOF)m/z:[M+H]+calcd.for C28H27O3Si+439.1724,found 439.1729.[α]21 d= +70.1 (c=1.0in ch2cl 2.) HPLC analysis 97% ee, [ chiral IB column; the flow rate was 0.5 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 13.0 min (minor peak), 14.3 min (major peak)].
EXAMPLE 17 preparation method of silicon center chiral molecular Compound 5
Pb (OAc) 4 (177.6 mg,0.4 mmol) was added to 2a (33.0 mg,0.1mmol,97% ee) of MeOH (1 mL) at zero degrees. The reaction mixture was then allowed to warm to room temperature and stirred for 48 hours. After complete consumption of 2a (monitored by TLC), the reaction was quenched with saturated sodium bicarbonate (10 mL) and then filtered through celite. The filtrate was extracted with EtOAc (10 mL. Times.3). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. The solvent was removed by filtration and reduced pressure to give a residue which was purified by column chromatography using petroleum ether/dichloromethane (v/v) =1/1 as eluent to give the desired product 5 (27.6 mg,0.077mmol,77% yield, 96% ee).
Compound 5:1H NMR (400 MHz, CDCl 3) δ10.0 (s, 1H), 8.07 (d, J=7.6 Hz, 1H), 7.97 (d, J=7.6 Hz, 1H), 7.56-7.33 (m, 11H), 3.53 (s, 3H), 0.94 (s, 3H); 13C {1H } NMR (100 MHz, CDCl 3) delta 193.0,168.2,141.4,140.8,139.0,138.0,137.5,137.3,135.9,135.1,132.9,131.7,130.8,130.2,129.4,129.3,129.0,127.8,51.7, -0.4.HRMS (ESI-TOF) M/z: [ M+H ] +calcd.for C22H21O3Si+361.1254,found 361.1262: [ alpha ]22D = +11.1 (c=1.0in CH2Cl 2): HPLC analysis 96% ee, [ chiral IC column; the flow rate was 1.0 ml/min; mobile phase isopropanol/n-hexane=10/90; retention time 7.5 min (minor peak), 9.0 min (major peak) ].
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.

Claims (9)

1. A preparation method of a silicon center chiral molecule compound is characterized by comprising the following synthetic routes:
wherein R is 1 Selected from C 1~12 Alkyl, C 2~12 Alkenyl, aryl or substituted aryl, halogen, C 1~10 One of the halogenated alkyl groups, the substituent in the substituted aryl group being selected from C 1~5 Alkoxy, C 1~3 Haloalkyl, halogen, C 1~10 An alkyl group; r is R 2 Is C 1~12 Alkyl, C 2~12 Alkenyl or cyclopropyl; r is R 3 Selected from hydrogen, C 1~6 Alkyl, C 1~5 Alkoxy, halogen, C 1~3 One of the haloalkyl groups;
the preparation method comprises the following steps:
the preparation method comprises the steps of (1) completely reacting a compound 1, a catalyst NHC and an alkaline reagent in an organic solution at 20-35 ℃ under the protection of inert gas, and separating and purifying to obtain the compound;
wherein the catalyst NHC is selected from any one of the following structures:
the alkaline reagent is selected from one or more of N, N-diisopropylethylamine, 1, 8-diazabicyclo undec-7-ene, 4-dimethylaminopyridine, cesium carbonate, sodium bicarbonate and sodium acetate.
2. The preparation method according to claim 1, wherein the organic solvent is one or more selected from dichloromethane, chloroform, toluene, tetrahydrofuran, ethyl acetate and acetonitrile.
3. The preparation method of claim 1, wherein the molar ratio of the compound 1 to the catalyst NHC to the alkaline reagent is 1:0.05-0.3:0.3-2.
4. The method according to claim 1, wherein the reaction time is 12 to 48 hours.
5. The method according to claim 1, wherein the inert gas is nitrogen or argon.
6. A silicon-centered chiral molecular compound characterized by having the structure shown in compound 2:
2
wherein R is 1 Selected from C 1~12 Alkyl, C 2~12 Alkenyl, phenyl or substituted phenyl, naphthyl, halogen, C 1~10 One of the halogenated alkyl groups, the substituent in the substituted phenyl group being selected from C 1~5 Alkoxy, C 1~3 Haloalkyl, halogen, C 1~10 An alkyl group; r is R 2 Is C 1~12 Alkyl, C 2~12 Alkenyl or cyclopropyl; r is R 3 Selected from hydrogen, C 1~6 Alkyl, C 1~5 Alkoxy, halogen, C 1~3 One of the haloalkyl groups.
7. The silicon-centered chiral molecular compound of claim 6, wherein R 1 Selected from C 1~6 Alkyl, vinyl, phenyl or substituted phenyl, naphthyl, C 1~10 One of the halogenated alkyl groups, wherein the substituent in the substituted phenyl group is selected from methoxy, trifluoromethyl, halogen and methyl; r is R 2 Is C 1~7 Alkyl, C 2~8 Alkenyl or cyclopropyl; r is R 3 One selected from hydrogen, methoxy, trifluoromethyl, halogen and methyl.
8. The silicon-centered chiral molecule compound of claim 7, wherein R 1 One selected from hexyl, vinyl, phenyl or substituted phenyl, naphthyl and chloromethane, wherein the substituent in the substituted phenyl is selected from methoxy, trifluoromethyl, halogen and methyl; r is R 2 Methyl, ethyl, n-butyl, isobutyl, isopropyl, cyclopropyl, vinyl; r is R 3 One selected from hydrogen, methyl, methoxy, trifluoromethyl and halogen.
9. Use of the silicon-centered chiral molecular compound according to any one of claims 6-8 for the preparation of chiral ligands containing silicon.
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