A general strategy for the amination of electron-rich and electron-poor heteroaromatics by desaturative catalysis

The introduction of alkylamines onto heteroaromatics is integral to the preparation of high-value molecules. Typical methods rely on heteroaromatic pre-functionalization by halogenation or nitration, followed by metal-catalysed cross-coupling or multi-step manipulation of the nitrogen functionality. This results in often unselective or low-yielding synthetic routes. Here we show an alternative approach in which saturated heterocyclic ketones are used as aryl surrogates for desaturative coupling with amines. The process operates under mild photochemical conditions, is compatible with complex amines and delivers both electron-poor and -rich heteroaromatics that are difficult to access by other methods. As ketones are readily decorated by carbonyl chemistry, this retrosynthetic tactic escapes the rules and limitations of aromatic reactivity and metal-catalysed cross-couplings. Our process uses enamine formation to create the key carbon–nitrogen bond, followed by two rounds of photoredox oxidation and cobalt-catalysed desaturation. The two desaturation steps are distinct, as the cobaloxime first acts as a hydrogen atom abstractor and then an oxidant.