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 CuBr 2 . 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.