Catalytic Asymmetric Mannich Reaction with N-Carbamoyl Imine Surrogates of Formaldehyde and Glyoxylate

Abstract

N,O-acetals (NOAcs) were developed as bench stable surrogates for N-carbamoyl, (Boc, Cbz and Fmoc) formaldehyde and glyoxylate imines in asymmetric Mannich reactions. The NOAcs can be directly utilized in the chiral primary amine catalyzed Mannich reactions of both acyclic and cyclic β-ketocarbonyls with high yields and excellent stereoselectivity. The current reaction offers a straightforward approach in the asymmetric synthesis of α- or β-amino carbonyls bearing chiral quaternary centers in a practical and highly stereocontrolled manner.

Keywords: Mannich reactions; N,O-acetals; amino carbonyls; enamine catalysis; imine surrogate.