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Enantioselective Synthesis of Pyroglutamic Acid Esters from Glycinate via Carbonyl Catalysis
Author(s) -
Ma Jiguo,
Zhou Qinghai,
Song Guanshui,
Song Yongchang,
Zhao Guoqing,
Ding Kuiling,
Zhao Baoguo
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202017306
Subject(s) - enantioselective synthesis , pyroglutamic acid , chemistry , electrophile , decarboxylation , diastereomer , catalysis , organic chemistry , amino acid , biochemistry
Direct α‐functionalization of NH 2 ‐free glycinates with relatively weak electrophiles such as α,β‐unsaturated esters still remains a big challenge in organic synthesis. With chiral pyridoxal 5 d as a carbonyl catalyst, direct asymmetric conjugated addition at the α‐C of glycinate 1 a with α,β‐unsaturated esters 2 has been successfully realized, to produce various chiral pyroglutamic acid esters 4 in 14–96 % yields with 81–97 % ee's after in situ lactamization. The trans and cis diastereomers can be obtained at the same time by chromatography and both of them can be easily converted into chiral 4‐substituted pyrrolidin‐2‐ones such as Alzheimer's drug Rolipram ( 11 ) with the same absolute configuration via tert ‐butyl group removal and subsequent Barton decarboxylation.