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

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.