Identification of Ammonium Chloride as an Effective Promoter of the Asymmetric Hydrogenation of a β-Enamine Amide

Abstract

An investigation into the cause of substrate specific hydrogenation performance variability was conducted. A significant and unexpected correlation was observed between apparent pH of a solution of the substrate and rate of conversion and enantioselectivity. This observation led to the examination of low and variable levels of native ammonium chloride in different lots of substrate. The presence of ammonium chloride was found to have a positive effect on reaction rate and enantioselectivity when controlled within a relatively narrow range. Optimal performance was achieved with a mole ratio of 1:1 ammonium chloride to catalyst.