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Pd‐Catalyzed Asymmetric Allylic Substitution Annulation Using Enolizable Ketimines as Nucleophiles: An Alternative Approach to Chiral Tetrahydroindoles
Author(s) -
Xu Kai,
Ye Jianxun,
Liu Hao,
Shen Jiefeng,
Liu Delong,
Zhang Wanbin
Publication year - 2020
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.202000151
Subject(s) - desymmetrization , annulation , chemistry , enantioselective synthesis , allylic rearrangement , nucleophile , combinatorial chemistry , nucleophilic substitution , catalysis , stereochemistry , organic chemistry , medicinal chemistry
A synthesis of chiral tetrahydroindoles has been developed via a Pd‐catalyzed asymmetric allylic substitution annulation using unstable enolizable ketimines as nucleophiles and our previously developed t Bu‐RuPHOX as a chiral ligand. The reaction proceeds via an asymmetric desymmetrization of the meso ‐diacetatecycloalkenes, providing the desired chiral tetrahydroindoles in moderate to good yields and with up to 96% ee. The annulation reaction could be performed on a gram‐scale in high yields and the resulting products can be transformed to several types of N ‐hetereobicyclic derivatives. In addition, a chiral cis ‐perhydroindolic acid derivative was also readily synthesized starting from a prepared chiral tetrahydroindole.