An asymmetric, bifunctional catalytic approach to non-natural α-amino acid derivatives

A catalytic, asymmetric process for the synthesis of 1,4-benzoxazinones from o-benzoquinone imides and ketene enolates is reported. Addition of Lewis acids (Zn(OTf)(2), In(OTf)(3), and in particular Sc(OTf)(3)) creates a bifunctional catalytic system that dramatically increases the reaction rate and the yield of these non-natural amino acid precursors while preserving the remarkable enantioselectivity inherent to the reaction. Cocatalyst Sc(OTf)(3) increases the yield by up to 42% while producing products in > 99% ee.