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One‐Pot N‐Deprotection and Catalytic Intramolecular Asymmetric Reductive Amination for the Synthesis of Tetrahydroisoquinolines
Author(s) -
Zhou Huan,
Liu Yuan,
Yang Suhua,
Zhou Le,
Chang Mingxin
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201611181
Subject(s) - tetrahydroisoquinoline , chemistry , intramolecular force , reductive amination , amination , stereoselectivity , catalysis , imine , combinatorial chemistry , iridium , enantioselective synthesis , organic chemistry
A one‐pot N‐Boc deprotection and catalytic intramolecular reductive amination protocol for the preparation of enantiomerically pure tetrahydroisoquinoline alkaloids is described. The iodine‐bridged dimeric iridium complexes displayed superb stereoselectivity to give tetrahydroisoquinolines, including several key pharmaceutical drug intermediates, in excellent yields under mild reaction conditions. Three additives played important roles in this reaction: Titanium(IV) isopropoxide and molecular iodine accelerated the transformation of the intermediate imine to the tetrahydroisoquinoline product; p ‐toluenesulfonic acid contributed to the stereocontrol.