Synthesis of Thioamides from the Cross-Coupling Reaction of Dithiocarbamates with Organotitanium and Organoalane Reagents

This work reports an efficient and straightforward cross-coupling method for synthesizing thioamide derivatives from dithiocarbamates and organoaluminum or organotitanium reagents, catalyzed by 6 mol % Pd(acac) 2 or Pd(OAc) 2 with 8 mol % DPPY. Under optimized conditions, the reactions afford thioamides in 18–96 and 14–97% yields, respectively. The protocol shows excellent functional group tolerance toward allyl, cyano, ketal, and electronically diverse aryl and heterocyclic organometallic reagents. Notably, bioactive thioamides bearing 4-(bis(4-fluorophenyl)methyl)piperazine and triazole units are successfully constructed. This approach avoids expensive Ir/Rh catalysts, requires no additional base, and remains efficient at gram scale, thus representing a practical synthetic route to thioamide derivatives. A plausible catalytic cycle is proposed based on experimental observations.