Nucleophilic addition of bulk chemicals with imines using N-functionalized hydroxylamine reagents as precursors.

Abstract

C-C and C-X bond forming reactions are essential tools in organic synthesis, constantly revolutionizing human life. Among the key methods for constructing new chemical bonds are nucleophilic addition reactions involving imines. However, the inherent challenges in synthesizing and storing imines have stimulated interest in designing stable precursors, which generates imines in situ during the reaction. This approach offers a promising alternative to traditional strategies and holds significant potential for future applications. Here we report a direct and general nucleophilic addition of imines with cost-effective feedstocks and easily accessible nucleophiles, specifically utilizing N‑functionalized hydroxylamine reagents as bench-stable precursors. This methodology streamlines the synthesis of various products, such as amino acid derivatives, through a wide range of reaction types, including C-C, C-N, C-O, and C-S bond constructions. Mechanistic studies and DFT calculations provide insights into a plausible reaction mechanism that supports the in-situ imine formation.