Brønsted Acid-Facilitated\nThioetherification\nCross-Coupling Reactions with Nickel and Visible Light

Transition metal-catalyzed\ncross-coupling reactions are\nessential\nin modern organic synthesis, facilitating the rapid creation of complex\nmolecular structures. Traditionally, these reactions rely heavily\non conventional bases, with only a few exceptions reported. Recently,\nwe developed adaptive dynamic homogeneous catalysis (AD-HoC), a method\nthat enables C(sp<sup>2</sup>)–S cross-couplings without needing\ntraditional ligands, bases, or additives. Given the growing demand\nfor protocols compatible with acidic conditions in metal-catalyzed\ncross-couplings, we revisited AD-HoC to pioneer acid-facilitated transition\nmetal-catalyzed thioetherification. Our method enables the swift synthesis\nof thioethers using nickel and visible light, with a substoichiometric\namount of Brønsted acid acting as an enabler. NMR kinetic studies\nindicate that in the absence of acid, the system displays an induction\nperiod characteristic of autocatalysis. Introducing the acid as a\nsimple additive eliminates this induction period and significantly\naccelerates the reaction. Moreover, the protocol has been successfully\nscaled to gram-level synthesis using continuous flow technology, achieving\nproductivities of over 100 g per hour in a commercially available\nlab-scale photoreactor. This highlights the method’s robustness\nand scalability, making it a powerful tool for large-scale applications.