Modular synthesis of heterobenzylic amines via Carbonyl Azinylative Amination

The synthesis of α-alkyl, α’-2-azinyl amines by addition of 2-heteroaryl-based nucleophiles to alkyl substituted iminium ion is typically a challenging synthetic transformation due to mismatched reactivities and competing deprotonation adja-cent to the carbon-nitrogen double bond. Here, we report a solution to this problem through the development of a multi-component coupling process wherein a putative 2-azinyl indium nucleophile, generated in situ from the corresponding 2-iodo heteroarene and indium powder, adds to an iminium ion that is also formed directly in the reaction. This modular and operationally straightforward carbonyl azinylative amination (CAzA) displays a broad scope, does not require a tran-sition metal catalyst and only a metal reductant is needed to generate a reactive 2-azinyl nucleophile in the reaction. Beyond the addition to iminium ions, the 2-azinylation of polyfluoromethyl ketones to form the corresponding tertiary al-cohols is also disclosed. Together, the products of these reactions possess a high degree of functionality, are typically challenging to synthesize by other methods, and contain motifs recognized as privileged in the context of pharmaceuti-cals and agrochemicals.