Synthesis of enantiopure 3,6,7,8-tetrahydrochromeno[7,8- d]imidazoles via asymmetric ketone hydrogenation in the presence of RuCl 2[Xyl-P-Phos][DAIPEN

Abstract

The asymmetric hydrogenation of complex heterocyclic ketones 1 in the presence of the novel catalyst RuCl 2[( S)-Xyl-P-Phos][( S)-DAIPEN] and a base afforded the corresponding alcohols 2 in good enantiomeric purity. The outcome of the reaction depended on the substitution pattern of the ketone and the stoichiometry of the base. After optimization of the reaction conditions, the pure alcohols 2a and 2b were isolated in good yield (>70%) and enantiomeric purity (>93% ee) and used as key intermediates for the synthesis of the pharmaceutically active 3,6,7,8-tetrahydrochromeno[7,8- d]imidazoles 3a and 3b.