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Electronically Activated Organoboron Catalysts for Enantioselective Propargyl Addition to Trifluoromethyl Ketones
Author(s) -
Mszar Nicholas W.,
Mikus Malte S.,
Torker Sebastian,
Haeffner Fredrik,
Hoveyda Amir H.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201703844
Subject(s) - enantioselective synthesis , trifluoromethyl , propargyl , chemistry , moiety , aryl , catalysis , silylation , yield (engineering) , alkyl , organic chemistry , combinatorial chemistry , materials science , metallurgy
A broadly applicable, practical, scalable, efficient and highly α‐ and enantioselective method for addition of a silyl‐protected propargyl moiety to trifluoromethyl ketones has been developed. Reactions, promoted by 2.0 mol % of a catalyst that is derived in situ from a readily accessible aminophenol compound at ambient temperature, were complete after only 15 minutes at room temperature. The desired tertiary alcohols were isolated in up to 97 % yield and 98.5:1.5 enantiomeric ratio. Alkyl‐, alkenyl‐, alkynyl‐, aryl‐ or heteroaryl‐substituted trifluoromethyl ketones can be used. Utility is highlighted by application to a transformation that is relevant to enantioselective synthesis of BI 653048, a compound active against rheumatoid arthritis.