Stop-Flow Microtubing Reactor-Assisted Visible Light-Induced Hydrogen-Evolution Cross Coupling of Heteroarenes with C(sp3)–H Bonds

The synthesis of valuable alkyl-substituted heteroarenes from abundant and inexpensive feedstocks under mild conditions is attractive and highly desirable in pharmaceutical and natural product synthesis. Minisci-type cross dehydrogenative coupling between heteroarenes and C(sp3)–H bonds offers direct access to these important scaffolds in a step-economic manner. Herein, assisted by stop-flow microtubing reactors, an operationally simple protocol for the visible light-induced hydrogen-evolution cross coupling of heteroarenes with unactivated C(sp3)–H bonds was developed in a metal- and external oxidant-free manner. A wide range of alkylated heteroarenes was generated with common feedstock chemicals, including ethane. Mechanistic studies indicated that photoredox-induced hydrogen atom transfer processes followed by dehydrogenative rearomatization delivered the desired coupling products. The merits of this strategy were further demonstrated by the late-stage functionalization of various complex bioactive molecules.