Formal Umpolung Strategy for the Synthesis of α‐Branched Amides via α‐Sulfenylnitro Compounds

Amide compounds are essential structural motifs found in natural products, pharmaceuticals, peptides and materials. A novel formal umpolung strategy for an efficient synthesis of α‐branched amides was developed, employing nitroalkenes, Grignard reagents and amines as reacting components. The synthesis involves the formation of α‐sulfenylnitro intermediates, which undergo oxidative amidation under optimized conditions using tert‐butyl hydroperoxide (TBHP) as an oxidant and K2CO3 as a base. The key intermediate, an α‐sulfenylnitro compound, was successfully synthesized in a one‐pot operation. This methodology demonstrates a broad substrate scope, accommodating various amines, including primary and secondary amines as well as amino acid derivatives, and yielding the corresponding α‐branched amides in high efficiency. The sulfenyl nitro scaffold proved particularly effective, offering both stability and reactivity. The developed process simplifies the preparation of α‐branched amides and expands the accessible structural diversity.