Metal- and photosensitizer-free cross-dehydrogenative coupling through photoinduced energy transfer

We developed metal- and photosensitizer-free cross-dehydrogenative coupling (CDC) systems to promote the cleavage of strong C(sp3)-H bonds through a distinct non-photoredox engaged hydrogen atom transfer (HAT) process. Mechanistic experiments indicate that this reaction predominantly proceeds through an energy transfer mechanism from excited-state heteroarenes to peroxides, with the direct irradiation of peroxides serving as a supplementary and secondary pathway to promote homolysis of the O-O bond. The resulting oxygen radicals undergo HAT from a substrate C-H bond, followed by addition of the obtained alky radical to heteroarenes, facilitating the formation of the key C-C bond. The conclusion that tert-butyl peroxybenzoate (TBPB) and heteroarenes are the optimal energy transfer pairs was drawn by screening a series of peroxides. In addition to its efficiency and step-economy, this approach boasts environmental advantages, making it suitable for the late-stage functionalization of pharmaceuticals and drug-like molecules, while accommodating a wide range of functional groups. This study introduces a novel, eco-friendly method for Minisci alkylation without harmful catalysts, advancing sustainable pharmaceutical synthesis through energy transfer from heteroarenes to peroxide, offering significant environmental benefits.