Ultrafast solvent- and metal-free coupling of thiols promoted by bromotrichloromethane and N,N-diisopropylethylamine

Abstract

This paper reported an ultrafast solvent- and metal-free method of constructing disulfide bonds (–S–S–) by oxidative homo- and cross-coupling of thiols with BrCCl₃ and DIPEA. This fast reaction successfully synthesized unsymmetric disulfides with high yields of up to 99% from benzylic, aryl and aliphatic thiols, without strong oxidant, metal-based reagents and catalysts. This direct disulfuration strategy was also applied to efficiently form symmetric disulfides. Our method was further capable of modifying or protecting cysteine derivatives and preparing protein inhibitors. This work provides a simple and efficient approach for constructing disulfide-containing compounds.