Reductive N-Alkylation of Amides with Carbonyl Compounds Using Copper(II) Bromide and 1,1,3,3-Tetramethyldisiloxane

Abstract

We report a reductive N-alkylation of amides using carbonyl compounds as alkylating agents and 1,1,3,3-tetramethyldisiloxane (TMDS) as the reducing agent with CuBr₂. The synthesis of secondary amides is essential in organic chemistry, and recently, some reductive N-alkylation of primary amides has been reported; however, previous methods require harsh conditions, such as high temperatures and/or pressures, and substrate compatibility is limited. Our method proceeds under mild reaction conditions and does not require toxic or expensive reagents. A range of substrates, including aromatic, aliphatic, and cinnamyl amides, as well as γ-lactams, afforded the corresponding alkylated amides in moderate to high yields. Notably, aldehydes and ketones can serve as alkylating agents in this transformation.