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Design and Synthesis of Chiral Diene Ligands for Rh I ‐Catalyzed Enantioselective Arylation of N ‐DPP‐protected Aldimines: Synthesis of the Antifungal Agent Bifonazole
Author(s) -
Syu JinFong,
Lin HuangYing,
Cheng YuYi,
Tsai YaoChu,
Ting YiChing,
Kuo TingShen,
Janmanchi Damodar,
Wu PingYu,
Henschke Julian P.,
Wu HsyuehLiang
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201702509
Subject(s) - aldimine , enantioselective synthesis , chemistry , diene , bifonazole , aryl , bifunctional , catalysis , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , antifungal , biology , natural rubber , alkyl , microbiology and biotechnology
Abstract Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the Rh I ‐catalyzed enantioselective addition reaction of arylboronic acids to N ‐diphenylphosphinyl ( N ‐DPP)‐protected aldimines. Unlike the analogous Rh I ‐catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N ‐DPP‐aldimines and arylboronic acids, producing the desired optically active N ‐DPP‐protected amines with yields between 31–99 % and with ee values up to 91–99 %. The synthetic utility of the method was demonstrated by the conversion of N ‐DPP‐protected amine 3 ae into the antifungal agent, bifonazole ( 13 ).