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Chiral Lewis Base‐Catalyzed, Enantioselective Reduction of Unprotected β‐Enamino Esters with Trichlorosilane
Author(s) -
Ye Jianheng,
Wang Chao,
Chen Lin,
Wu Xinjun,
Zhou Li,
Sun Jian
Publication year - 2016
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201501061
Subject(s) - chemistry , enantioselective synthesis , hydrosilylation , catalysis , formamides , organic chemistry , trichlorosilane , aryl , alkyl , asymmetric hydrogenation , combinatorial chemistry , organocatalysis , isopropyl , silicon
Catalytic asymmetric reduction of N‐unsubstituted β‐enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N‐unsubstituted β‐enamino esters has been developed. Using N ‐ tert ‐butylsulfinyl‐ L ‐proline‐derived amides and L ‐pipecolinic acid‐derived formamides as catalyst, a broad range of β‐aryl‐ and β‐alkyl‐substituted free β‐amino esters could be prepared with high yields and enantioselectivities. The practicality was illustrated by the gram‐scale asymmetric synthesis of ethyl ( R )‐3‐amino‐3‐phenylpropanoate and isopropyl ( S )‐3‐amino‐4‐(2,3,5‐trifluorophenyl)butanoate. The resulting product can be smoothly transformed to the FDA approved medicines dapoxetine and sitagliptin in a short synthetic route.