Method for efficiently synthesizing optically active 2-pyrroline compound through asymmetric organic phosphine catalyzing

A technology for pyrrolines and compounds, which is applied in the fields of organic chemistry, organic chemistry, bulk chemical production, etc. It can solve the problems of poor enantioselectivity and the development of synthetic methods for multi-substituted 2-pyrrolines, etc. Low cost, good industrial application prospects, and high catalytic efficiency

Active Publication Date: 2019-03-29
SOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

With the help of a new chiral phosphine catalyst, He Zhengjie et al. developed the cyclization reaction of MBH carbonate and α, β-unsaturated imine with high enantioselectivity and diastereoselectivity [1+4], α , the substituents on the nitrogen atom of the β-unsaturated imine have a great influence on the stereoselectivity of the phosphine-mediated cyclization, replacing 4-nitrobenzenesulfonyl with other groups (tosyl, benzenesulfonyl) Acyl groups lead to poor enantioselectivity
[0006] Therefore, the synthetic method of enantioselective synthesis of multi-substituted 2-pyrrolines remains to be developed

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for efficiently synthesizing optically active 2-pyrroline compound through asymmetric organic phosphine catalyzing
  • Method for efficiently synthesizing optically active 2-pyrroline compound through asymmetric organic phosphine catalyzing
  • Method for efficiently synthesizing optically active 2-pyrroline compound through asymmetric organic phosphine catalyzing

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] In a sealed tube under a nitrogen atmosphere, compound 1a (0.25 mmol), compound 2a (0.30 mmol), and catalyst I (10 mol%) in CH 2 Cl 2 The mixture in (2.0 mL) was stirred at 25°C for 48 h. After removing the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain the corresponding product 3aa.

[0035]

[0036] The yield is 46%, dr> 20:1, 88%ee.

[0037] White solid, mp 102.4-105.1℃. 1 H NMR(500Hz, CDCl 3 ):δ(ppm)7.71-7.68(m,2H),7.44-7.42(m,3H),7.31(d,J=8.0Hz,2H),7.12-6.99(m,5H),6.71(d,J =7.2Hz,2H),6.51(s,1H),6.28(s,1H), 5.28(d,J=3.6Hz,1H),5.01(d,J=2.8Hz,1H),4.07-3.95(m ,2H),3.62(t,J=3.4Hz,1H),2.40(s,3H),2.02-1.92(m,1H),0.95(d,J=6.8Hz,3H),0.94(d,J= 6.8Hz, 3H). 13 C NMR(100Hz, CDCl 3 ): δ (ppm) 165.8, 144.9, 143.9, 142.2, 141.1, 133.6, 132.7, 129.6, 129.1, 128.5, 128.2, 128.0, 127.9, 127.4, 126.3, 125.3, 116.1, 71.1, 69.7, 53.5, 27.8, 21.6, 19.2, 19.1. HRMS: accurate mass calculation [M+H] + (C 30 H 32 NO 4 S) is...

Embodiment 2

[0039] In a sealed tube under a nitrogen atmosphere, compound 1a (0.25 mmol), compound 2a (0.30 mmol), and catalyst II (10 mol%) in CH 2 Cl 2 The mixture in (2.0 mL) was stirred at 25°C for 48 h. After removing the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain the corresponding product 3aa.

[0040]

[0041] The yield is 6%, dr> 20:1, 86%ee.

Embodiment 3

[0043] In a sealed tube under a nitrogen atmosphere, compound 1a (0.25 mmol), compound 2a (0.30 mmol), and catalyst III (10 mol%) in CH 2 Cl 2 The mixture in (2.0 mL) was stirred at 25°C for 48 h. After removing the solvent, the crude residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate) to obtain the corresponding product 3aa.

[0044]

[0045] Yield 5%, dr> 20:1, 67%ee.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
particle size (mesh)aaaaaaaaaa
Login to View More

Abstract

The invention belongs to the field of an organic synthesis method, and discloses a method for efficiently synthesizing optically active 2-pyrroline compound through asymmetric organic phosphine catalyzing. The method is characterized by taking a chiral phosphine compound as a catalyst and enabling a compound as shown in a formula A which is shown in the description to react with a compound as shown in a formula B which is shown in the description, thus obtaining a compound as shown in a formula C which is shown in the description, wherein Ar<1> is selected from phenyl or substituted phenyl, Ar<2> is selected from phenyl or substituted phenyl, R<1> is selected from a sulfonyl protecting group, and R<2> is selected from alkyl or benzyl. The method disclosed by the invention is good in catalytic effect, a series of optically active polysubstituted 2-pyrroline can be obtained through enantioselective [1+4] cyclization of phosphine mediated MBH carbonate and alpha, beta-unsaturated imine, the yield is high, the stereoselectivity is good, the catalytic efficiency is good, the application range of a substrate is wide, the operation is simple, the cost is low, and a very good industrial application prospect is obtained.

Description

Technical field [0001] The invention belongs to the field of organic synthesis methods, in particular to a method for efficiently synthesizing optically active 2-pyrroline compounds through asymmetric organic phosphine catalysis. Background technique [0002] Chiral pyrroline and its derivatives are of great significance in natural products, drugs and enantioselective catalysis. Researchers are committed to developing asymmetric synthesis methods for pyrroline compounds. [0003] Organic phosphine-catalyzed enantioselective cyclization is an effective synthetic strategy. For example, organic phosphine-mediated asymmetric [3+2] cyclization of imines or alkynoates with imines can obtain optically active 3 -Pyrroline compounds, however, asymmetrically catalyzed [1+4] cyclization to synthesize chiral pyrroline has not been reported yet. [0004] In 2015, Gregory C.Fu et al. catalyzed the enantioselective [1+4] cyclization of cyclosulfonamide with γ-substituted allenes to synthesize 3-py...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & AuthorityApplications(China)
IPC IPC(8): C07D207/48
CPCC07B2200/07C07D207/48Y02P20/55
Inventor李鹏飞钱辰骁张庞淼淼
OwnerSOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA