Tripeptide-catalyzed Asymmetric Aldol Reaction of Trifluoromethylated Aromatic Ketones with Acetone

The development of H-Pro-Gly-Ala-OH (3d) to realize an inexpensive and simple organocatalytic system for the direct asymmetric aldol reaction of trifluoromethylated aromatic ketone 1 with acetone was achieved. The 3d-catalyzed aldol reaction of 1a-1j provided various aldol adducts 4a-4j with up to 81% yield and 77% ee. An investigation of the transition state via DFT calculations revealed that hydrogen bonding was important for the revelation of the enantioselectivity.