Protecting Groups as Catalysts: Direct Synthesis of Primary Amines from Ammonia under Carbonyl Catalysis

Abstract Primary amines are indispensable building blocks in pharmaceuticals, agrochemicals, and functional materials, yet their direct, modular synthesis from ammonia remains challenging. Here we report a carbonyl catalysis strategy that enables the direct synthesis of structurally complex primary amines from ammonia by integrating the conventional multistep sequence of protection, N–H functionalization, and deprotection into a single catalytic cycle. As a proof of concept, amino-trifluoromethylation of alkenes using ammonium salts and Togni reagent afforded a wide range of β-trifluoromethylated primary amines, including derivatives of complex natural products. 1,8-Diazafluorenone was uniquely competent as a carbonyl catalyst, highlighting the critical role of catalyst design in ammonia transformation. Mechanistic studies suggest that its distinctive electronic structure facilitates the formation of the N–H ketimine intermediate, a prerequisite for catalytic turnover. These findings establish carbonyl catalysis as a platform for the direct transformation of ammonia and demonstrate how protecting groups can function as catalysts.