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

作者：Iimuro Atsuhiro; Higashida Kosuke; Kita Yusuke; Mashima Kazushi^*

来源：Advanced Synthesis & Catalysis, 2016, 358(12): 1929-1933.

DOI：10.1002/adsc.201600203

• asymmetric catalysis
• hydrogenation
• iridium
• nitrogen heterocycles

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.

• 出版日期2016-6-16