CN110256479B - Chiral pyrrolidine derivative containing silicon acyl skeleton and preparation method thereof - Google Patents

Chiral pyrrolidine derivative containing silicon acyl skeleton and preparation method thereof Download PDF

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CN110256479B
CN110256479B CN201910339842.2A CN201910339842A CN110256479B CN 110256479 B CN110256479 B CN 110256479B CN 201910339842 A CN201910339842 A CN 201910339842A CN 110256479 B CN110256479 B CN 110256479B
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徐利文
马俊涵
杨雪敏
徐征
尹官武
郑战江
郭彬
崔玉明
曹建
叶飞
杨科芳
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Abstract

The invention relates to the field of catalytic chemistry, and particularly discloses a chiral pyrrolidine derivative containing a silicon acyl skeleton and a preparation method thereof, wherein the compound has a structure shown as a formula (I), and the preparation method comprises the following steps: under the protection of inert gas, mixing and stirring phosphine ligand, metal catalyst and reaction medium, then adding acylated silane compound, additive and azomethine ylide in turn, and making them pass through 1, 3-dipole [3+2]]The chiral pyrrolidine derivative containing the silicon acyl skeleton is obtained by cycloaddition reaction, the preparation method is simple to operate, the conditions are mild, the yield is good, the enantioselectivity is high, the obtained derivative contains a plurality of functional groups and a plurality of chiral centers, the potential biological activity is realized, the chiral pyrrolidine derivative can be used as a fine chemical intermediate to be widely applied to various organic reactions and drug synthesis, and the application value is considerable.
Figure DDA0002040362530000011

Description

Chiral pyrrolidine derivative containing silicon acyl skeleton and preparation method thereof
Technical Field
The invention relates to the field of catalytic chemistry, in particular to a chiral pyrrolidine derivative containing a silicon acyl skeleton and a preparation method thereof.
Technical Field
The pyrrole ring structure widely exists in a plurality of natural products and drug molecules, is an extremely important organic synthesis building block, and the pyrrolidine and the proline derivative also have obvious effects in organic small molecule catalysis, and show very high-efficiency catalytic activity and stereoselectivity in a plurality of asymmetric catalytic reactions.
Compounds containing chiral pyrrolidine units are particularly useful in medicine applications, such as: the medicine can treat cardiovascular and cerebrovascular diseases, is capable of relieving atrial premature beat and paroxysmal atrial tachycardia, and has good curative effect on supraventricular arrhythmia; torasemide for treating cardiovascular and cerebrovascular diseases has good curative effect on various edema diseases such as heart failure, chronic heart failure, liver ascites and the like; the anticancer drug gefitinib is a selective tyrosine kinase inhibitor.
In the aspect of pesticides, pyridine pesticides can effectively prevent and treat diseases caused by basidiomycetes, ascomycetes and deuteromycetes, and in the last 80 th century, people extract pyrrole antibiotic nitropyrrolidin from marine pseudomonas, then modify the pyrrole antibiotic nitropyrrolidin to develop a novel bactericide seed dressing, and further develop fluothalonil, thereby forming the series of bactericides.
Thus, many countries have invested a great deal of capital for the study of heterocyclic compounds, the design and synthesis of which has long been one of the research hotspots in the field of organic synthesis, particularly the design and synthesis of physiologically active heterocyclic compounds, as shown in figure a, which have been synthesized and tested in vitro for their ability to inhibit the enzyme activity of ACE (angiotensin converting enzyme) and exhibit the same potency as captopril; as shown in panel b below, the inhibitory effect of Angiotensin Converting Enzyme (ACE); as shown in figure c below, TAC101, an orally active agonist of the α and β subtypes of retinoic acid receptors, has now advanced to animal models of tumor growth and metastasis, with promising results in phase I clinical trials for lung cancer treatment; serine protease inhibitors as shown in panel d below.
Figure BDA0002040362510000021
At present, researchers have developed many methods for constructing such nitrogen-containing heterocycles, among which the 1, 3-dipolar cycloaddition reaction of methyleneamine ylide to olefins is widely used due to its high efficiency, high atom utilization, and green chemistry. The asymmetric catalytic synthesis method of the reaction is independently reported by topic groups of professors of Zhang Shumo and Jorgensen in 2002, and then international research groups follow up successively, including Carrereo, Fukuzawa, Schreiber and domestic topic groups of Zhouyougui, Wangchunjiang and the like, and a plurality of efficient catalytic systems and reaction models are developed successively. Not only many ligands with different structures are used, but also many kinds of metal catalysts are used, including Zn, Ag, Cu, Au, Ni, and the like.
Disclosure of Invention
The invention aims to provide a chiral pyrrolidine derivative containing a silicon acyl skeleton, which contains a plurality of functional groups and a plurality of chiral centers, has potential biological activity, can be widely used in various organic reactions and drug synthesis as a fine chemical intermediate, and has considerable application value.
The invention also aims to provide a preparation method for synthesizing the chiral pyrrolidine derivative containing the silicon acyl skeleton by the asymmetric 1, 3-dipolar [3+2] cycloaddition reaction catalyzed by transition metal, and the preparation method has the advantages of simple operation, mild condition, better yield and extremely high enantioselectivity.
The invention is realized by the following technical scheme:
a chiral pyrrolidine derivative containing a silicon acyl skeleton has a structure shown as a formula (I):
Figure BDA0002040362510000031
in the formula, a substituent R1Is alkyl or is unsubstitutedOr phenyl substituted by alkyl, haloalkyl or halogen; substituent R2Is alkyl, naphthyl or is phenyl which is unsubstituted or substituted by alkyl, alkoxy or halogen atoms.
Further, the substituent R1Is C1～C6Alkyl is unsubstituted or substituted by C1～C3Alkyl radical, C1～C3A haloalkyl group or a phenyl group substituted with a halogen atom; substituent R2Is C1～C3Alkyl, naphthyl or unsubstituted or substituted by C1～C3Alkyl radical, C1～C3Alkoxy or phenyl substituted by halogen atoms.
Wherein "C" is1～C6The alkyl group means a straight-chain or branched alkyl group having 1 to 6 carbon atoms; "haloalkyl" refers to an alkyl group in which the hydrogen atom is replaced with a halogen atom; "halogen atom" means fluorine, chlorine, bromine, iodine and astatine atoms.
The compound prepared by the invention has groups such as silicon group, ester group, silicon acyl group and the like, and the unique property of the silyl group ensures that the compound has good lipophilicity and can effectively improve the stability of self metabolism; the ester group makes it very hydrophilic. In addition, silicon groups can be converted into various functional groups through reaction, when the silicon groups are converted into hydrogen, aldehyde pyrrole ring compounds can be formed, and when the silicon groups are converted into hydroxyl, proline-like structural compounds can be formed; the acyl group-containing pyrrole can be desiliconized to convert to a benzoin pyrrole ring compound.
The preparation method of the chiral pyrrolidine derivative containing the sulfonyl skeleton comprises the following steps: under the protection of inert gas, mixing and stirring a phosphine ligand, a metal catalyst and a reaction medium, sequentially adding an acylated silane compound shown in a formula (II), an additive and a azomethine ylide shown in a formula (III), and carrying out 1, 3-dipolar [3+2] cycloaddition reaction to obtain a chiral pyrrolidine derivative containing a silicon acyl skeleton, wherein the reaction formula is shown as follows:
Figure BDA0002040362510000041
r in the formula (II)1And R in the formula (III)2The definition of (A) is the same as in formula (I).
The method takes easily synthesized methyl imine ylide and acylated silane compounds as raw materials, and efficiently synthesizes a series of chiral pyrrolidine derivatives containing the silicon acyl skeleton through asymmetric 1, 3-dipolar [3+2] cycloaddition reaction catalyzed by transition metal for the first time. The complex formed by the metal catalyst and the phosphine ligand in situ is used as a catalytic precursor, the catalytic precursor participates in a catalytic circulation system, the catalytic efficiency is high, and a target product with high yield can be obtained; and the additive is used to control the stereo configuration of the product, so as to obtain the target product with high enantioselectivity.
The methyl imine ylide and the acylated silane compounds are used as raw materials, the reaction is easy to synthesize, the operation is simple, the post-treatment is convenient, and the products with better yield and enantioselectivity are obtained.
The phosphine ligand is any one of compounds shown as formulas L1-L4:
Figure BDA0002040362510000042
preferably, the phosphine ligand is L2, L3 or L4, the complex formed in situ by the specific metal catalyst and the phosphine ligand is used as a catalytic precursor, the operation is simple, the catalytic precursor participates in a catalytic circulation system, the catalytic efficiency is high, and the target product with higher yield and enantioselectivity can be obtained.
The metal catalyst is a mixture of silver carbonate and a copper catalyst, and the copper catalyst is selected from any one of cuprous bromide, copper tetraacetonitrile hexafluorophosphate, copper tetraacetonitrile tetrafluoroborate, copper acetate or copper trifluoromethanesulfonate.
Preferably, the metal catalyst is a mixture of silver carbonate and copper tetraacetonitrile hexafluorophosphate, because the combination of the two metal catalysts can be better combined with ligand, and the yield and enantioselectivity are improved.
The additive is any one of potassium phosphate, monopotassium phosphate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium tetraarylborate, cesium carbonate, triethylamine, N-Diisopropylethylamine (DIPEA) or 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU).
Preferably, the additive is potassium carbonate, because the preferred additive can not only control the spatial configuration of the product so as to improve the enantioselectivity of the target product, but also improve the yield of the target product.
The molar ratio of the acylated silane compound to the azomethine ylide, the phosphine ligand, the metal catalyst and the additive is 1: (1.2-1.5): (0.02-0.2): (0.03-0.06): (0.1-0.15).
The reaction medium is any one of toluene, tetrahydrofuran, dichloromethane or diethyl ether.
The reaction temperature is 0-30 ℃, the reaction time is 20-30 h, the reaction conditions are mild, the reaction can be completed by stirring at room temperature, the operation is simple, and the method is suitable for large-scale production and application.
After the reaction is finished, the chiral pyrrolidine derivative containing the silicon acyl skeleton is obtained through post-treatment, wherein the post-treatment comprises the following steps: extracting with ethyl acetate, drying the organic phase, removing the solvent by rotary evaporation, and separating and purifying the crude product by silica gel column chromatography.
Compared with the prior art, the invention has the beneficial effects that:
(1) the method has simple operation, can complete the reaction by stirring at room temperature, can obtain a pure product by performing rapid column chromatography impurity removal on a crude product and then performing reduced pressure concentration, is convenient for post-treatment, and obtains the chiral pyrrolidine derivative with a series of polyfunctional groups and chiral centers, high yield and high enantioselectivity.
(2) The product containing multifunctional group and chiral center pyrrole rings obtained by the method of the invention is pyrrole antibiotic and can be used as broad-spectrum antifungal drugs. The derivative contains a plurality of functional groups and a plurality of chiral centers, has potential biological activity, can be widely applied to the fields of various organic syntheses, medicines, material chemistry and fine chemical industry, and has considerable application value;
drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of chiral pyrrolidine derivative 6a containing a silicon acyl skeleton obtained in example 1;
FIG. 2 is a nuclear magnetic carbon spectrum of chiral pyrrolidine derivative 6a containing a silicon acyl skeleton obtained in example 1.
Detailed Description
The present invention is further illustrated by the following examples, in which the starting materials are either commercially available or prepared by conventional methods.
Example 1:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to a test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and acylated silane compound 4a (0.20mmol) were stirred at room temperature for 24h, after the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 62.6mg of pale yellow solid 6a in 82% yield and 98% ee.
Figure BDA0002040362510000061
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3)δ251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5,-4.2.
high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated value 82.1833, found value: 382.1830. specific optical rotation:
Figure BDA0002040362510000072
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
HRMS(ESI,m/z)calculated for C22H28NO3Si[M+H]+Calculated 82.1833, found 382.1830.
Figure BDA0002040362510000073
(c＝3.66,CHCl3).Mp 88-90℃.Enantiomeric excess was determined by HPLC with a Phenomenex Lux 5u Cellulose column(hexanes:2-propanol＝80:20,1.0mL/min,210nm,98％ee)；major enantiomer tr＝5.96min,minor enantiomer tr＝32.18min.
Example 2:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4b (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was performed with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 45.0mg of white solid 6b in 50% yield and 92% ee.
Figure BDA0002040362510000071
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.54(t,J＝8.8,4H),7.39(t,J＝7.6Hz,4H),7.33(d,J＝6.8Hz,1H),4.33(t,J＝8.1Hz,1H),4.13(t,J＝9.2Hz,1H),3.98(t,J＝9.2Hz,1H),3.27(s,1H),2.80(s,1H),-0.30(s,2H).13C NMR(101MHz,CDCl3)δ250.5,172.9,143.6,140.4,129.7(d,J＝32.3Hz),129.0,128.6,128.4,127.1,125.4(q, J4.0 Hz),124.1(d, J272.7 Hz),68.7,66.9,65.1,52.4,51.7, -4.1. high resolution mass spectrometry (ESI, m/z): c23H27F3NO3Si[M+H]+ calculated value 450.1707, found value: 450.1703. specific optical rotation:
Figure BDA0002040362510000082
(c＝1.12,CHCl3). Melting point: 110 ℃ and 112 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 92% ee); the major enantiomer tr was 5.18 min and the minor enantiomer tr was 22.60 min.
Example 3:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4c (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 59.1mg of white solid 6b in 71% yield and 94% ee.
Figure BDA0002040362510000081
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.51(d,J＝7.6Hz,2H),7.36(t,J＝7.6Hz,2H),7.30(d,J＝7.6Hz,1H),7.22(dd,J＝20.0,8.4Hz,4H),4.32(d,J＝7.6Hz,1H),4.27(d,J＝7.6Hz,1H),4.09(t,J＝9.6Hz,1H),3.88(t,J＝9.6Hz,1H),3.29(s,3H),2.73(s,1H),-0.30(s,9H).13C NMR(101MHz,CDCl3) δ 250.4,173.0,140.7,137.8,133.1,129.5,128.8,128.4,128.1,126.9,68.7,66.6,65.0,52.2,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H27ClNO3Si[M+H]+ calculated value 416.1443, findThe value: 416.1436. specific optical rotation:
Figure BDA0002040362510000092
(c＝1.33,CHCl3). Melting point: 117 ℃ and 119 ℃. Liquid chromatography using Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 85:15,0.8mL/min,210nm, 94% ee) to determine enantiomeric excess; the major enantiomer tr was 7.74 min and the minor enantiomer tr 39.76 min.
Example 4:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4d (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 39.6mg of a white solid 6d in 83% yield and 98% ee.
Figure BDA0002040362510000091
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.52(d,J＝7.6Hz,2H),7.35(t,J＝7.2Hz,2H),7.29(d,J＝7.2Hz,1H),7.09(dd,J＝22.4,8.0Hz,4H),4.35(d,J＝8.8Hz,1H),4.25(d,J＝8.8Hz,1H),4.17(t,J＝9.6Hz,1H),3.88(t,J＝9.6Hz,1H),3.26(s,3H),2.72(s,1H),2.28(s,3H),-0.30(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.9,136.8,135.6,128.9,128.8,128.0,127.0,68.7,66.7,65.2,53.1,51.4,21.0, -4.2. high resolution mass spectrometry (ESI, m/z): c23H30NO3Si[M+H]+ calculated value 396.1989, found value: 396.1986. specific optical rotation:
Figure BDA0002040362510000102
(c＝1.20,CHCl3). Melting point: 108-110 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.59 min and the minor enantiomer tr 31.33 min.
Example 5:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4e (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 55.3mg of 6e as a white solid in 60% yield and 98% ee.
Figure BDA0002040362510000101
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.49(d,J＝7.6Hz,2H),7.39(d,J＝8.4Hz,2H),7.35(t,J＝8.0Hz,2H),7.29(t,J＝7.2Hz,1H),7.13(d,J＝8.0Hz,2H),4.31(d,J＝6.4Hz,1H),4.26(d,J＝7.6Hz,1H),4.07(t,J＝9.2Hz,1H),3.85(t,J＝9.2Hz,1H),3.30(s,3H),2.50(s,1H),-0.30(s,9H).13C NMR(101MHz,CDCl3) δ 250.73,173.14,140.68,138.41,131.54,129.93,128.95,128.27,127.01,121.31,68.83,66.78,65.08,52.35,51.73, -4.06. high resolution mass spectrometry (ESI, m/z): c22H27BrNO3Si[M+H]+ calculated value 460.0938, found value: 460.0926. specific optical rotation:
Figure BDA0002040362510000103
(c＝1.23,CHCl3). Melting point: 113 ℃ and 115 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); master and slaveLet tr equal 6.29 min for the minor enantiomer and tr equal 32.15 min.
Example 6:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4f (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 59.1mg of 6f as a pale yellow solid in 74% yield and 96% ee.
Figure BDA0002040362510000111
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.52(d,J＝7.6Hz,2H),7.36(t,J＝7.2Hz,2H),7.29(dd,J＝9.6,6.8Hz,2H),7.20(dd,J＝14.0,7.2Hz,1H),7.06(t,J＝7.2Hz,1H),7.00(t,J＝10,1H),4.38–4.25(m,3H),4.21(t,J＝9.2Hz,1H),3.26(s,3H),2.60(s,1H),-0.26(s,9H).13C NMR(101MHz,CDCl3) δ 250.5,173.4,160.0(d, J248.5 Hz),140.8,129.1,129.0,128.8(d, J4.0 Hz),128.3,127.4,125.9(d, J19.2), 124.1(d, J4.0 Hz),115.4(d, J23.2 Hz),67.1,66.9,64.2,51.6,45.6, -4.0. high resolution mass spectrometry (ESI, m/z): c22H27FNO3Si[M+H]+ calculated value 400.1739, found value: 460.1754. specific optical rotation:
Figure BDA0002040362510000112
(c＝1.58,CHCl3). Melting point: 123 ℃ and 125 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol: 85:15,0.8mL/min,210nm, 96% ee); the major enantiomer tr was 7.86 min and the minor enantiomer tr was 36.53 min.
Example 7:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and 4g (0.20mmol) of the acylated silane compound were reacted at room temperature with stirring for 24 hours. After the end of the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 55.7mg of a pale yellow solid 6g, 67% yield and 96% ee.
Figure BDA0002040362510000121
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.42(d,J＝7.2Hz,2H),7.28–7.12(m,5H),7.06(t,J＝7.2Hz,1H),7.02(t,J＝7.2Hz,1H),4.44(t,J＝9.6Hz,1H),4.32(d,J＝9.2Hz,1H),4.21(d,J＝9.2Hz,1H),4.08(t,J＝9.6Hz,1H),3.08(s,3H),2.58(s,1H),-0.38(s,9H).13C NMR(101MHz,CDCl3) δ 250.1,173.5,140.9,136.5,134.8,129.5,128.8,128.4,128.2,127.8,127.1,126.7,67.0,66.9,63.2,51.4,48.4, -3.9. high resolution mass spectrometry (ESI, m/z): c22H27ClNO3Si[M+H]+ calculated value 416.1443, found value: 416.1442. specific optical rotation:
Figure BDA0002040362510000122
(c＝1.26,CHCl3). Melting point: 126 ℃ and 128 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 96% ee); the major enantiomer tr was 6.31 min and the minor enantiomer tr 13.01 min.
Example 8:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol), acylating the silane compound for 4h (0.20mmol), and stirring at room temperature for 24 h. After the reaction was monitored by TLC, extraction was performed with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 70.9mg of a white solid for 6h, 77% yield, 96% ee.
Figure BDA0002040362510000131
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.54(t,J＝7.2Hz,3H),7.37(dd,J＝14.0,7.2Hz,3H),7.31(d,J＝7.2Hz,1H),7.24(t,J＝7.2Hz,1H),7.07(t,J＝7.6Hz,1H),4.56(t,J＝9.2Hz,1H),4.47(d,J＝9.6Hz,1H),4.34(d,J＝9.2Hz,1H),4.20(t,J＝9.6Hz,1H),3.22(s,3H),2.72(s,1H),-0.25(s,9H).13C NMR(101MHz,CDCl3) δ 250.1,173.5,140.8,138.3,132.9,128.8,128.7,128.2,127.9,127.3,127.1,125.7,67.4,66.9,63.3,51.4,51.1, -3.9. high resolution mass spectrometry (ESI, m/z): c22H27BrNO3Si[M+H]+ calculated value 460.0938, found value: 460.0917. specific optical rotation:
Figure BDA0002040362510000132
(c＝1.02,CHCl3). Melting point: 116 ℃ and 118 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 96% ee); the major enantiomer tr was 6.68 min and the minor enantiomer tr 10.82 min.
Example 9:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4i (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the end of the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 47.7mg of 6i as an orange oil in 53% yield and 92% ee.
Figure BDA0002040362510000141
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.74(d,J＝7.6Hz,1H),7.62(d,J＝7.6Hz,1H),7.58–7.48(m,3H),7.42–7.29(m,4H),4.43–4.32(m,2H),4.30(d,J＝8.8Hz,1H),4.14(t,J＝9.2Hz,1H),3.19(s,3H),2.39(s,1H),-0.36(s,9H).13C NMR(101MHz,CDCl3) δ 250.3,173.0,140.3,139.1,131.8,129.1(d, J ═ 29.3Hz),128.8,128.4,128.3,127.1,127.1,125.8(q, J ═ 6.1Hz),124.1(d, J ═ 274.7Hz),69.5,67.3,65.2,51.4,47.6, -4.4. high resolution mass spectrometry (ESI, m/z): c22H27BrNO3Si[M+H]+ calculated value 450.1707, found value: 450.1685. specific optical rotation:
Figure BDA0002040362510000142
(c＝2.18,CHCl3). The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 92% ee); the major enantiomer tr was 6.03 min and the minor enantiomer tr was 7.47 min.
Example 10:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and 4j (0.20mmol) of the acylated silane compound, and the reaction was stirred at room temperature for 24 hours. After the reaction was monitored by TLC, it was extracted with ethyl acetate, the organic phase was dried and removed by rotary evaporationThe crude product was isolated and purified by silica gel column chromatography to give 43.3mg of 6j as a white solid in 52% yield and 98% ee.
Figure BDA0002040362510000151
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.52(d,J＝7.2Hz,2H),7.37(t,J＝7.2Hz,2H),7.30(t,J＝7.2Hz,1H),7.24–7.19(m,3H),7.17–7.12(m,1H),4.28(t,J＝9.6Hz,2H),4.12(t,J＝9.6Hz,1H),3.89(t,J＝9.2Hz,1H),3.32(s,3H),2.21(s,1H),-0.30(s,9H).13C NMR(101MHz,CDCl3) δ 250.7,173.2,140.9,140.5,134.2,129.6,128.9,128.2,127.5,127.0,126.3,68.2,66.9,65.0,52.7,51.6, -4.2. high resolution mass spectrometry (ESI, m/z): c22H27ClNO3Si[M+H]+ calculated value 416.1443, found value: 416.1432. specific optical rotation:
Figure BDA0002040362510000152
(c＝0.35,CHCl3). Melting point: 104-106 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 6.74 min and the minor enantiomer tr 57.74 min.
Example 11:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and base K2CO3(0.02mmol) and 4k (0.20mmol) of the acylated silane compound were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, it was extracted with ethyl acetate, the organic phase was dried and the solvent removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 32.8mg of a pale yellow solid 6k in 40% yield and 98% ee.
Figure BDA0002040362510000161
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝7.2Hz,2H),7.37(t,J＝7.2Hz,2H),7.31(d,J＝7.2Hz,1H),7.11(dd,J＝19.2,8.0Hz,4H),4.35(d,J＝9.6Hz,1H),4.26(d,J＝9.2Hz,1H),4.17(t,J＝9.6Hz,1H),3.90(t,J＝9.6Hz,1H),3.26(s,3H),2.59(q,J＝7.6Hz,2H),2.01(s,1H),1.18(t,J＝7.6Hz,3H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.3,173.7,143.6,141.0,135.9,128.9,128.5,127.8,127.1,68.7,66.9,65.4,53.4,51.6,28.6,15.8, -4.1. high resolution mass spectrometry (ESI, m/z): c24H32NO3Si[M+H]+ calculated value 410.2146, found value: 410.2137. specific optical rotation:
Figure BDA0002040362510000162
(c＝0.43,CHCl3). Melting point: 73-75 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 4.80 min and the minor enantiomer tr 22.57 min.
Example 12:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding 5l (0.30mmol) of glycine Schiff base and K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the end of the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 51.9mg of 6l as a white solid in 65% yield and 94% ee.
Figure BDA0002040362510000171
The physical and chemical properties of the productMarking:1H NMR(400MHz,CDCl3)δ7.53(t,J＝7.6Hz2H),7.25(m,3H),7.07(t,J＝8.4Hz,2H),4.37(d,J＝5.5Hz,1H),4.28(d,J＝6.7Hz,1H),4.15(t,J＝9.4Hz,1H),3.90(t,J＝9.5Hz,1H),3.26(s,2H),2.60(s,1H),-0.29(s,5H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,162.5(d, J-247.5 Hz),138.5,136.7(d, J-2.0 Hz),128.6(d, J-8.1 Hz),128.4,128.1,127.4,115.6(d, J-21.2 Hz),68.4,65.8,65.0,53.3,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H27FNO3Si[M+H]+ calculated value 400.1724, found value: 400.1739. specific optical rotation:
Figure BDA0002040362510000172
(c＝0.83,CHCl3). Melting point: 110 ℃ and 112 ℃. Liquid chromatography using Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 94% ee) to determine enantiomeric excess; the major enantiomer tr was 5.16 min and the minor enantiomer tr 10.51 min.
Example 13:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5m (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 54.1mg of a white solid 6m in 65% yield and 94% ee.
Figure BDA0002040362510000181
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.49(d,J＝8.4Hz,2H),7.35(d,J＝8.4Hz,2H),7.31–7.19(m,5H),4.40(d,J＝9.3Hz,1H),4.28(d,J＝9.3Hz,1H),4.13(t,J＝9.6Hz,1H),3.87(t,J＝9.6Hz,1H),3.26(s,2H),2.67(s,1H),-0.28(s,9H).13C NMR(101MHz,CDCl3) δ 250.7,173.2,139.6,138.5,133.7,128.9,128.4,128.4,128.1,127.5,68.3,65.5,65.0,53.2,51.5, -4.1. high resolution mass spectrometry (ESI, m/z): c22H27FNO3Si[M+H]+ calculated value 416.1443, found value: 416.1440. specific optical rotation:
Figure BDA0002040362510000182
(c＝0.63,CHCl3). Melting point: 108-110 ℃. Liquid chromatography using Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 94% ee) to determine enantiomeric excess; the major enantiomer tr was 6.04 min and the minor enantiomer tr 10.0 min.
Example 14:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5n (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 70.0mg of white solid 6b in 76% yield and 94% ee.
Figure BDA0002040362510000191
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.50(d,J＝8.0Hz,2H),7.43(d,J＝8.0Hz,2H),7.33–7.17(m,5H),4.39(s,1H),4.28(s,1H),4.11(t,J＝8.0Hz,1H),3.87(t,J＝8.0Hz,1H),3.26(s,3H),2.69(s,1H),-0.27(s,9H).13C NMR(101MHz,CDCl3) δ 250.8,172.7,140.2,138.6,132.0,128.8,128.5,128.2,127.6,121.8,68.5,67.0,65.5,53.5,51.62, -4.00. high resolution mass spectrometry (ESI, m/z): c22H27FNO3Si[M+H]+ calculated value 460.0938, found value: 460.0932. specific optical rotation:
Figure BDA0002040362510000192
(c＝4.40,CHCl3). Melting point: 92-94 ℃. Liquid chromatography using Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 94% ee) to determine enantiomeric excess; the major enantiomer tr was 6.14 min and the minor enantiomer tr 9.83 min.
Example 15:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5o (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 57.0mg of a pale yellow solid 6b in 72% yield and 98% ee.
Figure BDA0002040362510000201
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.41(d,J＝7.6Hz,2H),7.31–7.21(m,5H),7.19(t,J＝8.4Hz,3H),4.31(d,J＝8.4Hz,1H),4.28(d,J＝8.4Hz,1H),4.17(t,J＝9.2Hz,1H),3.92(t,J＝9.6Hz,1H),3.25(s,3H),2.71(s,1H),2.35(s,3H),-0.30(s,9H).13C NMR(101MHz,CDCl3) δ 251.1,173.4,138.8,137.8,137.4,129.4,128.3,128.1,127.3,126.8,68.6,66.7,65.2),53.4,51.5,21.2, -4.2. high resolution mass spectrometry (ESI, m/z): c23H30NO3Si[M+H]+ calculated value: 396.1989, find the value: 396.1956. specific optical rotation:
Figure BDA0002040362510000202
(c＝0.56,CHCl3). Melting point: 72-74 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 6.10 min and the minor enantiomer tr 35.44 min.
Example 16:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5p (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 51.0mg of 6p as a white solid in 62% yield and 96% ee.
Figure BDA0002040362510000211
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.46(d,J＝8.4Hz,2H),7.30–7.19(m,5H),6.90(d,J＝8.4Hz,2H),4.29(d,J＝9.6Hz,1H),4.25(d,J＝9.6Hz,1H),4.17(t,J＝10.0Hz,1H),3.92(t,J＝9.6Hz,1H),3.81(s,3H),3.24(s,3H),2.50(s,1H),-0.29(s,9H).13C NMR(101MHz,CDCl3) δ 251.4,173.6,159.6,139.0,128.4,128.2,128.2,127.4,114.2,68.7,66.6,65.3,55.4,53.5,51.6, -4.0. high resolution mass spectrometry (ESI, m/z): c23H30NO4Si[M+H]+ calculated value: 412.1939, find the value: 412.1930. specific optical rotation:
Figure BDA0002040362510000212
(c＝5.88,CHCl3). Melting point: 75-77 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 96% ee); major enantiomer tr 7.92 min, timesLet the enantiomer tr 28.61 min.
Example 17:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5q (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 44.3mg of a white solid 6q, 56% yield, 92% ee.
Figure BDA0002040362510000221
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.98(d,J＝8.0Hz,1H),7.33(t,J＝7.6Hz,1H),7.31–7.16(m,7H),7.11(d,J＝7.6Hz,1H),4.61(d,J＝9.2Hz,1H),4.30(d,J＝9.6Hz,1H),4.25(t,J＝9.6Hz,1H),3.97(t,J＝10.0Hz,1H),3.24(s,3H),2.24(s,3H),-0.32(s,9H).13C NMR(101MHz,CDCl3) δ 251.4,173.7,138.9,138.7,136.0,130.7,128.5,128.2,127.8,127.5,126.9,126.5,68.4,65.5,62.6,54.0,51.6,19.7, -4.2. high resolution mass spectrometry (ESI, m/z): c23H30NO4Si[M+H]+ calculated value: 396.1989, find the value: 396.1978. specific optical rotation:
Figure BDA0002040362510000222
(c＝1.09,CHCl3). Melting point: 106-108 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 92% ee); the major enantiomer tr was 6.22 min and the minor enantiomer tr 25.45 min.
Example 18:
under a nitrogen atmosphere, the phosphine ligand (R) -XylbINAP (7) was added to the test tube.3mg,0.01mmol), metal catalyst Ag2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5r (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 62.2mg of 6r as a white solid in 72% yield and 92% ee.
Figure BDA0002040362510000231
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.89(d,J＝8.8Hz,2H),7.84(dd,J＝5.6,3.6Hz,2H),7.75(d,J＝8.4Hz,1H),7.48(p,J＝6.6Hz,2H),7.27(t,J＝4.4Hz,4H),7.22(td,J＝8.4,4.0Hz,1H),4.58(d,J＝9.2Hz,1H),4.34(d,J＝9.2Hz,1H),4.28(t,J＝9.6Hz,1H),3.94(t,J＝9.6Hz,1H),3.28(s,3H),2.75(s,1H),-0.34(s,9H).13C NMR(101MHz,CDCl3) δ 251.2,173.4,139.0,138.3,133.5,133.3,128.9,128.5,128.3,128.0,127.8,127.5),126.4,126.1,125.8),124.9,68.6,66.7,65.4,53.5,51.6, -4.0. high resolution mass spectrometry (ESI, m/z): c26H30NO3Si[M+H]+ calculated value: 432.1989, find the value: 432.1978. specific optical rotation:
Figure BDA0002040362510000232
(c＝1.28,CHCl3). Melting point: 120-122 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 92% ee); the major enantiomer tr was 7.31 min and the minor enantiomer tr was 12.09 min.
Example 19:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5s (0.30mmol) and base K2CO3(0.02mmol) and the acylated silane compound 4a (0.20mmol) were reacted at room temperature with stirring for 24 hours. After the reaction was monitored by TLC, extraction was performed with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 50.6mg of a white solid 6s in 64% yield and 98% ee.
Figure BDA0002040362510000241
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.35–7.19(m,8H),7.11(d,J＝7.2Hz,1H),4.31(d,J＝9.6Hz,1H),4.27(d,J＝9.6Hz,1H),4.17(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.56(s,1H),2.37(s,3H),-0.30(s,9H).13C NMR(101MHz,CDCl3) δ 251.2,173.4,140.5,138.9,138.4,128.8,128.7,128.3,128.1,127.6,127.3,123.9),68.7,66.9,65.3),53.5,51.5,21.4, -4.2. high resolution mass spectrometry (ESI, m/z): c23H30NO3Si[M+H]+ calculated value: 396.1989, find the value: 396.1973. specific optical rotation:
Figure BDA0002040362510000242
(c＝0.86,CHCl3). Melting point: 116 ℃ and 120 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 6.21 min and the minor enantiomer tr was 50.94 min.
Example 20:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to the test tube2CO3(1.7mg,0.006mmol),Cu(CH3CN)4PF6(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5t (0.30mmol) and base K2CO3(0.02mmol), acylation of silane Compound 4a (0.20mmol), Room temperatureThe reaction was stirred for 24 h. After the end of the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 49.7mg of a pale yellow solid 6t, 54% yield and 94% ee.
Figure BDA0002040362510000251
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.67(s,1H),7.48(d,J＝7.6Hz,1H),7.44(d,J＝7.6Hz,1H),7.34–7.17(m,6H),4.39(d,J＝8.8Hz,1H),4.28(d,J＝8.8Hz,1H),4.12(t,J＝9.6Hz,1H),3.85(t,J＝9.6Hz,1H),3.27(s,3H),2.43(s,1H),-0.26(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.2,143.6,138.6,131.2,130.5,130.1,128.5,128.2,127.6,125.6,122.9,68.4,65.7,65.1,53.3,51.6, -4.1. high resolution mass spectrometry (ESI, m/z): c22H27BrNO3Si[M+H]+ calculated value: 460.0938, find the value: 462.0988. specific optical rotation:
Figure BDA0002040362510000252
(c＝0.82,CHCl3). Melting point: 120 ℃ and 121 ℃. Liquid chromatography using Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 94% ee) to determine enantiomeric excess; the major enantiomer tr was 5.30 min and the minor enantiomer tr was 11.16 min.
Example 21:
adding a phosphine ligand PPh into a test tube under the nitrogen atmosphere3(1.0mg,0.004mmol), Ag as a metal catalyst2CO3(0.6mg,0.002mmol),Cu(CH3CN)4BF4(0.6mg,0.002mmol) and 0.2mL of solvent toluene, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.24mmol) and KHCO base3(0.026mmol) and acylated silane compound 4a (0.20mmol) were reacted at 0 ℃ with stirring for 20 hours. After the completion of the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was purified by silica gel column chromatography to give 53.3mg of white solid 6a in 70% yield as a racemic product。
Figure BDA0002040362510000261
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+ calculated value: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000262
(c＝3.66,CHCl3). Melting point: 88-90 ℃. Liquid chromatography using Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm,0ee) to determine enantiomeric excess; the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 22:
under nitrogen atmosphere, phosphine ligand (R) -Segphos (13.4mg,0.022mmol) and metal catalyst Ag were added to a test tube2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol) and 0.4mL solvent dichloromethane, stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.26mmol) and Na2CO3(0.03mmol) and the acylated silane compound 4a (0.20mmol) were reacted at 30 ℃ for 30 hours with stirring, after the completion of the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 57.1mg of a pale yellow solid 6a in 75% yield and 98% ee.
Figure BDA0002040362510000271
Physicochemical properties of the productIndexes are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000272
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 23:
phosphine ligand (R) -BINAP (13.7mg,0.022mmol), metal catalyst Ag were added to a test tube under nitrogen atmosphere2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol) and 2mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.3mmol) and base Cs2CO3(0.02mmol) and acylated silane compound 4a (0.20mmol) were stirred at room temperature for 24h, after the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 60.9mg of pale yellow solid 6a in 80% yield and 98% ee.
Figure BDA0002040362510000281
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000282
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 24:
phosphine ligand (R) -BINAP (13.7mg,0.022mmol), metal catalyst Ag were added to a test tube under nitrogen atmosphere2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol), 2mL solvent tetrahydrofuran, pre-stirred at room temperature for 30min, then glycine Schiff base 5a (0.3mmol), base Et were added sequentially3N (0.02mmol) and the acylated silane compound 4a (0.20mmol) were stirred at room temperature for 24h, after the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 55.6mg of a pale yellow solid 6a in 73% yield and 98% ee.
Figure BDA0002040362510000291
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific rotationLuminosity:
Figure BDA0002040362510000292
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 25:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to a test tube2CO3(1.7mg,0.006mmol), CuBr (0.80.006 mmol), 2.0mL solvent tetrahydrofuran, pre-stirred at room temperature for 30min, and sequentially added with glycine Schiff base 5a (0.30mmol) and base K3PO4(0.02mmol) and the acylated silane compound 4a (0.20mmol) were stirred at room temperature for 24h, after the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 49.6mg of a pale yellow solid 6a in 65% yield and 98% ee.
Figure BDA0002040362510000301
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000302
(c＝3.66,CHCl3). Melting point: 88-90 ℃. Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol: 80:20,1.0 mL-min,210nm, 98% ee) to determine the enantiomeric excess; the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 26:
under nitrogen atmosphere, phosphine ligand (R) -Xylbinap (7.3mg,0.01mmol), metal catalyst Ag was added to a test tube2CO3(1.7mg,0.006mmol),Cu(OAc)2(1.1mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and KH as base2PO4(0.02mmol) and acylated silane compound 4a (0.20mmol) were stirred at room temperature for 24h, after the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 55.0mg of pale yellow solid 6a in 72% yield and 98% ee.
Figure BDA0002040362510000311
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000312
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 27:
adding phosphine ligand (R) -ion into the test tube under nitrogen atmosphereXylBINAP (7.3mg,0.01mmol), metallic catalyst Ag2CO3(1.7mg,0.006mmol),Cu(OTf)2(2.2mg,0.006mmol) and 2.0mL tetrahydrofuran as solvent, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol) and NaBPh as base4(0.02mmol) and acylated silane compound 4a (0.20mmol) were stirred at room temperature for 24h, after the reaction was monitored by TLC, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 56.5mg of pale yellow solid 6a in 74% yield and 98% ee.
Figure BDA0002040362510000321
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000322
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 28:
under nitrogen atmosphere, phosphine ligand (R) -Segphos (13.4mg,0.022mmol) and metal catalyst Ag were added to a test tube2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol) and 2.0mL of solvent ether, pre-stirring at room temperature for 30min, and sequentially adding glycine Schiff base 5a (0.30mmol), base DIPEA (0.02mmol) and acylThe silane compound 4a (0.20mmol) was stirred at room temperature for 24h, after TLC monitoring of the reaction, extraction was performed with ethyl acetate, the organic phase was dried and the solvent was removed by rotary evaporation, and the crude product was isolated and purified by silica gel column chromatography to give 63.4mg of a pale yellow solid 6a with a yield of 83% and 98% ee.
Figure BDA0002040362510000331
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000332
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 29:
under nitrogen atmosphere, phosphine ligand (R) -Segphos (13.4mg,0.022mmol) and metal catalyst Ag were added to a test tube2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol) and 2.0mL of solvent diethyl ether are stirred at room temperature for 30min, then glycine Schiff base 5a (0.30mmol), base DBU (0.02mmol) and acylated silane compound 4a (0.20mmol) are added in sequence, stirred at room temperature for reaction for 24h, after the reaction is monitored by TLC, ethyl acetate is used for extraction, the solvent is removed by rotary evaporation after the organic phase is dried, and the crude product is separated and purified by silica gel column chromatography to obtain 61.1mg of gray yellow solid 6a, the yield is 80%, and 98% ee is obtained.
Figure BDA0002040362510000341
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)δ7.53(d,J＝6.0Hz,2H),7.36(s,2H),7.32–7.07(m,6H),4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,140.7,138.8,128.8,128.3,128.1,127.4,127.0,68.6,66.9,65.2,53.4,51.5, -4.2. high resolution mass spectrometry (ESI, m/z): c22H28NO3Si[M+H]+Calculated values: 382.1833, find the value: 382.1830. specific optical rotation:
Figure BDA0002040362510000343
(c＝3.66,CHCl3). Melting point: 88-90 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.96 min and the minor enantiomer tr was 32.18 min.
Example 30:
under nitrogen atmosphere, phosphine ligand (R) -Segphos (13.4mg,0.022mmol) and metal catalyst Ag were added to a test tube2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol) and 2.0mL of solvent diethyl ether are stirred at room temperature for 30min, then glycine Schiff base 5u (0.30mmol), base DBU (0.02mmol) and acylated silane compound 4l (0.20mmol) are added in sequence, stirred at room temperature for reaction for 24h, after the reaction is monitored by TLC, ethyl acetate is used for extraction, the solvent is removed by rotary evaporation after the organic phase is dried, and the crude product is separated and purified by silica gel column chromatography to obtain 61.1mg of gray yellow solid 6l, the yield is 80%, and 98% ee is obtained.
Figure BDA0002040362510000342
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),1.06(d,J＝9.6Hz,3H),0.93(d,J＝9.6Hz,3H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,68.6,66.9,65.2,53.4,51.5,22.1,18.4, -4.2. high resolution mass spectrometry (ESI, m/z): c12H23NO3Si[M+H]+Calculated values: 257.4050, find the value: 257.4044. specific optical rotation:
Figure BDA0002040362510000352
(c＝3.66,CHCl3). Melting point: 120-122 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.84 min and the minor enantiomer tr 17.66 min.
Example 31:
under nitrogen atmosphere, phosphine ligand (R) -Segphos (13.4mg,0.022mmol) and metal catalyst Ag were added to a test tube2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol) and 2.0mL of solvent diethyl ether are stirred at room temperature for 30min, then glycine Schiff base 5u (0.30mmol), base DBU (0.02mmol) and acylated silane compound 4m (0.20mmol) are added in sequence, stirred at room temperature for reaction for 24h, after the reaction is monitored by TLC, ethyl acetate is used for extraction, the solvent is removed by rotary evaporation after the organic phase is dried, and the crude product is separated and purified by silica gel column chromatography to obtain 61.1mg of gray yellow solid 6m, the yield is 80%, and 98% ee is obtained.
Figure BDA0002040362510000351
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),1.31(s,2H),1.25(s,2H),1.19(s,2H),1.06(d,J＝9.6Hz,3H),0.88(d,J＝9.6Hz,3H),-0.31(s,9H).13C NMR(101MHz,CDCl3)δ251.0,173.4,63.7,51.9,48.1,40.0,297,29.3,26.4,23.0,14.1-4.2. high resolution mass spectrometry (ESI, m/z): c12H23NO3Si[M+H]+Calculated values: 299.4860, find the value: 299.4844. specific optical rotation:
Figure BDA0002040362510000362
(c＝3.66,CHCl3). Melting point: 99-102 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.66 min and the minor enantiomer tr 19.22 min.
Example 32:
under nitrogen atmosphere, phosphine ligand (R) -Segphos (13.4mg,0.022mmol) and metal catalyst Ag were added to a test tube2CO3(5.5mg,0.02mmol),Cu(CH3CN)4PF6(7.5mg,0.02mmol) and 2.0mL of solvent ether are stirred for 30min at room temperature, then glycine Schiff base 5u (0.30mmol), base DBU (0.02mmol) and acylated silane compound 4n (0.20mmol) are sequentially added, the mixture is stirred for reaction for 24h at room temperature, after the reaction is monitored by TLC, ethyl acetate is used for extraction, the solvent is removed by rotary evaporation after an organic phase is dried, and the crude product is separated and purified by silica gel column chromatography to obtain 61.1mg of gray yellow solid 6n, wherein the yield is 80% and 98% ee is obtained.
Figure BDA0002040362510000361
The physical and chemical indexes of the product are as follows:1H NMR(400MHz,CDCl3)4.35(d,J＝9.6Hz,1H),4.28(d,J＝9.6Hz,1H),4.18(t,J＝9.6Hz,1H),3.92(t,J＝9.6Hz,1H),3.24(s,3H),2.58(s,1H),1.26(s,4H),1.25(s,4H),1.19(s,2H),1.06(d,J＝9.6Hz,3H),0.88(d,J＝9.6Hz,3H),-0.31(s,9H).13C NMR(101MHz,CDCl3) δ 251.0,173.4,68.6,66.9,65.2,53.4,51.5,31.8,29.7,29.6,27.1,26.7,22.7,22.1,18.4,14.1-4.2. high resolution mass spectrometry (ESI, m/z): c12H23NO3Si[M+H]+Calculated values: 327.5400, find the value: 327.5500. specific optical rotation:
Figure BDA0002040362510000363
(c＝3.66,CHCl3). Melting point: 105 ℃ and 106 ℃. The enantiomeric excess was determined by liquid chromatography on a Phenomenex Lux 5u Cellulose column (n-hexane: isopropanol 80:20,1.0mL/min,210nm, 98% ee); the major enantiomer tr was 5.11 min and the minor enantiomer tr was 20.87 min.
The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the claims of the present invention.

Claims (6)

1. A preparation method of chiral pyrrolidine derivative containing a silicon acyl skeleton comprises the following steps: under the protection of inert gas, mixing and stirring a phosphine ligand, a metal catalyst and a reaction medium, sequentially adding an acylated silane compound shown in a formula (II), an additive and a azomethine ylide shown in a formula (III), and carrying out 1, 3-dipolar [3+2] cycloaddition reaction to obtain the chiral pyrrolidine derivative containing the silicon acyl skeleton and having the structure shown in the formula (I), wherein the reaction formula is shown as follows:
Figure FDA0003348972860000011
in the formula (I), the substituent R1Is alkyl or is phenyl which is unsubstituted or substituted by alkyl, haloalkyl or halogen atoms; substituent R2Is alkyl, naphthyl or is phenyl which is unsubstituted or substituted by alkyl, alkoxy or halogen atoms;
r in the formula (II)1And R in the formula (III)2Is as defined in formula (I);
the phosphine ligand is any one of compounds shown as formulas L2-L4:
Figure FDA0003348972860000012
the metal catalyst is a mixture of silver carbonate and copper tetra-acetonitrile hexafluorophosphate;
the additive is potassium carbonate.
2. The method for producing a chiral pyrrolidine derivative having a sulfonyl skeleton according to claim 1, wherein the substituent R is1Is C1～C6Alkyl is unsubstituted or substituted by C1～C3Alkyl radical, C1～C3A haloalkyl group or a phenyl group substituted with a halogen atom; substituent R2Is C1～C3Alkyl, naphthyl or unsubstituted or substituted by C1～C3Alkyl radical, C1～C3Alkoxy or phenyl substituted by halogen atoms.
3. The method for preparing chiral pyrrolidine derivative having a silicon acyl skeleton according to claim 1, wherein the molar ratio of the acylated silane compound to the azomethine ylide, the phosphine ligand, the metal catalyst and the additive is 1: (1.2-1.5): (0.02-0.2): (0.03-0.06): (0.1-0.15).
4. The method for preparing chiral pyrrolidine derivative having a sulfonyl skeleton according to claim 1, wherein the reaction medium is selected from any one of toluene, tetrahydrofuran, dichloromethane or diethyl ether.
5. The method for preparing chiral pyrrolidine derivative containing a sulfonyl skeleton according to claim 1, wherein the reaction temperature is 0-30 ℃ and the reaction time is 20-30 h.
6. The method for preparing a chiral pyrrolidine derivative containing a sulfonyl skeleton according to claim 1, wherein the chiral pyrrolidine derivative containing a sulfonyl skeleton is obtained by post-treatment after the reaction, and the post-treatment comprises: extracting with ethyl acetate, drying the organic phase, removing the solvent by rotary evaporation, and separating and purifying the crude product by silica gel column chromatography.
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CN109096167A (en) * 2018-07-03 2018-12-28 杭州师范大学 A kind of more carbonyl official substituted chiral pyrrolidin derivatives and preparation method thereof
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CN1203586A (en) * 1995-11-30 1998-12-30 曾尼卡有限公司 Preparation of chiral 3-hydroxy-2-pyrrolidinone derivatives
WO2001058588A1 (en) * 2000-02-10 2001-08-16 The Penn State Research Foundation Chiral ferrocene phosphines and their use in asymmetric catalytic reactions
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