Photocatalytic Coupling of Phenols with Imines via Polarity Reversal

Abstract

A polarity-reversed coupling of phenols with imines is reported by means of photocatalytic conditions. Using the intrinsic redox potentials of both partners, coupling of the polarity-matched phenoxyl and α-amino radicals can be achieved in moderate to high yields without the need for exogenous oxidants or reductants. Both the ortho- and para-products can be obtained. However, the para-product dominates if both sites are available, complementing other known methods in literature that typically favor ortho- functionalization. The method exhibits good functional group tolerance for both phenol and imine substrates, including heteroaryl aldimines. This method was applied to the synthesis of pharmaceutically relevant compounds, as shown by synthesis of an NSC321578 fragment, without the need for pre-functionalization of the phenolic substrate.