Pd-Catalyzed Arylative Lossen Rearrangement: Synthesis of Secondary Amines from Aryl/Alkyl Carboxylic Acids and Aryl...

Carboxylic acids and their derivatives constitute one of the most diverse and readily accessible classes of synthetic building blocks and are ubiquitous in pharmaceuticals and natural products. Here we report a Pd-catalyzed decarboxylative coupling of hydroxamic acids with aryl electrophiles in which palladium orchestrates both the Lossen rearrangement and the cross-coupling process. This approach enables carboxylic acid derivatives to function as surrogates for primary amines, providing a complementary and powerful route to secondary amines. The reaction is effective across a broad range of hydroxamic acids and aryl (pseudo)halides, including both alkyl and aryl hydroxamic acids as well as aryl chlorides, bromides, and triflates, and exhibits broad functional group compatibility. Mechanistic studies support a dual role of Pd in the catalytic cycle, implicating Pd(II) species as the key promoter of the Lossen rearrangement in addition to the involvement in the C-N coupling step.