An innovative strategy for radical-mediated, bidirectional controlled disulfide exchange.

Metathesis reactions that operate cleanly and reversibly under biocompatible conditions are crucial in diverse fields such as drug development, chemical biology, and dynamic combinatorial chemistry. This paper introduces an innovative strategy using the commercially available and cost-effective hydroxy(tosyloxy)iodobenzene (HTIB) as a radical initiator, enabling clean and bidirectional disulfide metathesis under biocompatible conditions. Our method facilitates efficient forward reactions by utilizing an excess of one disulfide to shift the equilibrium toward unsymmetrical disulfides, while also ensuring clean reverse reactions by the removal of low boiling point dimethyl disulfide.