A general carbonyl alkylative amination for tertiary amine synthesis facilitated by visible light

The ubiquity of tertiary alkylamines in pharmaceutical and agrochemical agents, natural products and smallmolecule biological probes(1,2) continues to stimulate enormous efforts towards their streamlined synthesis(3–9). Arguably, the most robust method for tertiary alkylamine synthesis is carbonyl reductive amination(3): comprising two elementary steps, condensation of a secondary alkylamine with an aliphatic aldehyde forms an all alkyl-iminium ion, which is reduced by a hydride reagent. Chemists have sought to develop direct strategies for a ‘higher order’ variant of this reaction via the union of an alkyl fragment with an in-situ generated all alkyl-iminium ion(10–14). However, despite more than 70 years of research, the successful realization of a ‘carbonyl alkylative amination’ has remained elusive. Herein, we report that a practical and general solution can be accomplished by the addition of alkyl-radicals to all alkyl-iminium ions. The process is facilitated by visible-light and a silane reducing agent, which, together with the other reaction components, trigger a distinct radical initiation step to establish a chain process. An attractive feature of this operationally straightforward, metal-free and modular transformation is the unbiased nature of tertiary amines that arise from the traceless union of aldehydes and secondary amines with alkyl-halides. As such, the structural and functional diversity within these classes of abundant feedstocks provides a versatile and flexible strategy for the streamlined synthesis of complex tertiary amines.