Synergistic Catalytic Asymmetric Decarboxylative Mannich Reaction of β-Ketoacids with Acyclic α-Arylenamides

The asymmetric addition reactions of β-ketoacids to acyclic ketimines provide a direct means to afford versatile quaternary center-bearing amino compounds, but such an approach remains a formidable challenge. Here, we describe an efficient asymmetric catalytic decarboxylative Mannich reaction of β-ketoacids with acyclic α-arylenamides, which serve as the precursor of acyclic ketimines. By combining chiral binaphthyl phosphoric acids (CPAs) and simple copper salts as dual catalysts, a variety of optically active, acyclic, and quaternary carbon-containing β-aminoketones could be formed in up to 95% yield and 94% ee. Detailed mechanistic study suggests that mono-CPA-ligated copper and free CPA serve as synergistic catalysts to enhance the enantioselectivity. Furthermore, optically active β-amino acid and β-amino alcohol derivatives could be prepared via a simple transformation of the Mannich adducts.