A feasibility study on the synthesis of phenylephrine via ruthenium-catalyzed homogeneous asymmetric hydrogenation

Abstract

We report a feasibility study on a new route to ( R)-phenylephrine, based on the ruthenium-catalyzed asymmetric hydrogenation of an aminoketone precursor. The direct and fast asymmetric reduction of aminoketones or their hydrochloride salts is achievable at low catalyst loadings (molar substrate to catalyst ratio, S/C, >25,000/1, TOF up to 25,000 h −1) with high enantioselectivity (>95% ee), without the need for N-protection nor isolation of the free base prior to reaction.