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.