Enantioselective Cross-Aldol Reaction with Ketones and Non-Enolizable Ketones Catalyzed by Tetrapeptides

An efficient strategy shaping the construction of (R)-3-alkyl-3-hydroxyindolin-2-one and (S)-5-trifluoromethyl-4-hydroxy-4-arylpentan-2-one derivatives catalyzed by the beta-turn tetrapeptide catalyst under mild conditions was developed. Various isatins and ketones could participate in this reaction, and the desired adducts were obtained with excellent yield (up to 99 %) and moderate to high enantioselectivity (ee up to 85 %) and excellent diastereoselectivity (dr up to >20 : 1). Moreover, a series of trifluoromethyl ketones with ketones also could participate in this reaction, and the resulting beta-trifluoromethyl-beta-hydroxy ketones with excellent yields and moderate enantioselectivities (ee up to 58 %) were obtained. In addition, the strategy afforded better results than natural papain.

Automated summary

An efficient strategy has been developed for the construction of (R)-3-alkyl-3-hydroxyindolin-2-one and (S)-5-trifluoromethyl-4-hydroxy-4-arylpentan-2-one derivatives catalyzed by the beta-turn tetrapeptide catalyst, yielding high product yields with good enantioselectivity.