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. Issue 12 (2nd June 2016)

• Record Type: Journal Article
• Authors: Iimuro, Atsuhiro; Higashida, Kosuke; Kita, Yusuke; Mashima, Kazushi
• Is Part Of: Advanced synthesis & catalysis. Volume 358:Issue 12(2016)
• Page Start: 1929
• Page End: 1933
• Publication Date: 2016-06-02
• Subjects: asymmetric catalysis -- hydrogenation -- iridium -- nitrogen heterocycles; Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201600203
• Languages: English
• ISSNs: 1615-4150

Abstract

Abstract: 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. Abstract :