Catalytic ReductiveAza-Boron-Wittig Reaction

Despite the challenges of directly employing inert amide as the substrate in organic synthesis, developing a catalytic amide derivatization method has still attracted intense attention due to amide’s abundance and ease of handling. Herein, we describe a reductive aza-boron-Wittig reaction to convert amides and lactams to vinyl boronates. In contrast to the traditional boron-Wittig reaction, the catalytic reductive aza-version provides advantages including the ready availability of amides and high stereoselectivity of products. Synthetic utility is demonstrated by (1) directly deriving DMF and other naturally occurring amides to value-added molecules; (2) late-stage functionalization of complex structures; and (3) concise synthesis of drug molecules. Detailed mechanistic studies confirm that hemiaminal, iminium, and beta-aminoboronate are three key sequential intermediates. It has been shown that beyond aldehyde and ketone, iminium from the in situ reduction of amide can also serve as the viable substrate in the boron-Wittig reaction.