Asymmetric enamide hydrogenation in the synthesis of N-acetylcolchinol:: a key intermediate for ZD6126

A synthesis of N-acetylcolchinol, a key intermediate in the synthesis of ZD6126, was developed. The enantiodifferentiating step required the catalytic asymmetric hydrogenation of an enamide. After screening a range of metal and ligand combinations it was found that (S,S)-Pr-i-FerroTANE Ru(methallyl)(2) and [(S,S)-'BuFerroTANE Rh(COD)]BF4 gave both high enantioselectivity (>90% ee) and high catalyst utility (molar S/C= 1000). (c) 2007 Elsevier Ltd. All rights reserved.