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Asymmetric Hydrogenation of 3‐Amido‐2‐arylpyridinium Salts by Triply Chloride‐Bridged Dinuclear Iridium Complexes Bearing Enantiopure Diphosphine Ligands: Synthesis of Neurokinin‐1 Receptor Antagonist Derivatives
Author(s) -
Iimuro Atsuhiro,
Higashida Kosuke,
Kita Yusuke,
Mashima Kazushi
Publication year - 2016
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.201600203
Subject(s) - enantiopure drug , chemistry , iridium , asymmetric hydrogenation , enantioselective synthesis , stereochemistry , medicinal chemistry , combinatorial chemistry , organic chemistry , catalysis
We describe a most straightforward synthetic method for preparing neurokinin‐1 (NK1) receptor antagonist derivatives by asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts using dinuclear iridium complexes with enantiopure diphosphine ligands, affording the corresponding chiral piperidines in high cis ‐diastereoselectivity (>95:5) and moderately high enantioselectivity (up to 86%). Deprotection treatments afforded the NK‐1 receptor antagonist (+)‐CP‐99,994 (83% ee ). In addition, we observed unique additive effects of 10‐camphorsulfonic acid in the asymmetric hydrogenation of 3‐amido‐2‐arylpyridinium salts.