General Method for the Synthesis of Enaminones via Nickel Photocatalysis

Enaminones are key intermediates in the synthesis of several derivatives with important applications in medicinal chemistry. Furthermore, many marketed drugs feature the enamine structural moiety. In this context, we have developed a photoredox and nickel catalytic system to rapidly forge the enaminone scaffold from 3-bromochromones via the formation of a nitrogen-centered radical and subsequent trapping by the electron-deficient alkene moiety. With this dual catalytic system, a range of structurally diverse enaminone derivatives have been achieved in good yields with total trans selectivity. Mechanistic studies indicate that the key to the success of this process is the formation of an unexplored ternary Ni-complex with 3-bromochromone and a pyridinium salt, which is crucial for the effective activation of the a,b-unsaturated system towards the radical addition.