Ru-catalyzed asymmetric hydrogenation of δ-keto Weinreb amides: enantioselective synthesis of (+)-Centrolobine

An efficient asymmetric hydrogenation of delta-keto Weinreb amides catalyzed by a Ru-Xyl-SunPhos-Daipen bifunctional catalyst has been achieved. This method afforded a series of enantio-enriched delta-hydroxy Weinreb amides in good yields (up to 93%) and enantioselectivities (up to 99%). This protocol was successfully applied to the synthesis of the key intermediate of (+)-Centrolobine.