H₂O₂-Mediated Oxidative S-H/P(O)-H Cross-Coupling to Access Thiophosphates

Thiophosphates represent important scaffolds that find extensive applications in pharmaceutical development and organic synthesis. However, the development of general and sustainable synthetic approaches to those compounds remains scarce. Herein, an atom-economic H₂O₂-mediated oxidative S-H/P(O)-H cross-coupling with H₂O as the byproduct, and Et₃N/air-mediated dehydrogenative cross-coupling of thiols and trialkyl phosphites(III) have been developed for the construction of thiophosphates. These environmentally benign and mild strategies exhibited exceptional functional group compatibility and providing access to a wide array of S-P architectures (46 examples, yields up to 95%). Crucially, both methods feature operational simplicity, facile scalability, and direct applicability to bioactive molecule synthesis. Detailed mechanistic studies indicated that a radical pathway was involved in the synthesis of thiophosphates.