Green and sustainable site- and cross-selective C-H reductive coupling of para-quinone methides with quinoxaline-2(1H)-ones

We herein disclose a novel activation mode for quinoxaline-2(1 H )-ones via selective hydrogen atom transfer (HAT) of the N=C sp 2 -H bonds by synergistic photoredox catalysis and bromine radical catalysis, and applied it to the reductive coupling reaction of quinoxalinones with para -quinone methides ( p -QMs). The reaction proceeds through HAT of quinoxalinones and proton-coupled electron transfer (PCET) of p -QMs that establishes a radical-radical cross-coupling pathway between an imine radical and a diarylmethane radical in a metal-free manner. This practical and mild photoredox/HAT co-catalyzed radical-coupling protocol enables facile access to a wide array of C( sp 2 )−C( sp 3 ) cross-coupling products with broad substrate scope in excellent site- and cross-selective fashion. We illustrate the practicality of this approach for the late-stage functionalization of drugs and natural products. A highly selective, practical and economically efficient approach for facile assembly of bioactive quinoxalinized diarylmethanes by synergistic photocatalysis and bromine-based HAT catalysis is disclosed. This protocol does not require transition metals or excess oxidants and uses easy-to-synthesize starting-materials with excellent scalability and broad substrate scope. This transformation shows excellent functional-group compatibility and can be used for late-stage functionalization of drugs and natural products.