biostudies-literatureAmber CNIGMS NIH HHS17655-17663https://www.ebi.ac.uk/biostudies/studies/S-EPMC11624976biostudies-literatureUnknown89(23)Given its relevance across numerous fields, reductive amination is one of the oldest and most widely used methods for amine synthesis. As a cornerstone of synthetic chemistry, it has largely remained unchanged since its discovery over a century ago. Herein, we report the mechanistically driven development of a complementary reaction, which reductively aminates the C-C σ-bond of carbonyls, not the carbonyl C-O π-bond, generating value-added linear and cyclic 3° amines in a modular fashion. Critical to our success were mechanistic insights that enabled us to modulate the resting state of a borane catalyst, minimize deleterious disproportionation of a hydroxylamine nitrogen source, and control the migratory selectivity of a key nitrenoid reactive intermediate. Experiments support the reactionThe Journal of organic chemistryReductive Amination of Carbonyl C-C Bonds Enables Formal Nitrogen Insertion.PMC11624976R35 GM130345Petitjean TMSarpong RGottemann LTAmber CSteele RTfalseReductive Amination of Carbonyl C-C Bonds Enables Formal Nitrogen Insertion.Given its relevance across numerous fields, reductive amination is one of the oldest and most widely used methods for amine synthesis. As a cornerstone of synthetic chemistry, it has largely remained unchanged since its discovery over a century ago. Herein, we report the mechanistically driven development of a complementary reaction, which reductively aminates the C-C σ-bond of carbonyls, not the carbonyl C-O π-bond, generating value-added linear and cyclic 3° amines in a modular fashion. Critical to our success were mechanistic insights that enabled us to modulate the resting state of a borane catalyst, minimize deleterious disproportionation of a hydroxylamine nitrogen source, and control the migratory selectivity of a key nitrenoid reactive intermediate. Experiments support the reaction2024-01-01T00:00:00Z2024 Dec2025-04-18T13:08:37.502Z2025-04-06T22:40:37.151ZS-EPMC116249763950934410.1021/acs.joc.4c02400