Diaryl and Heteroaryl Sulfides: Synthesis via Sulfenyl Chlorides and Evaluation as Selective Anti-Breast-Cancer Agents

ABSTRACT: A mild protocol for the synthesis of diaryl and heteroaryl sulfides is described. In a one-pot procedure, thiols are converted to sulfenyl chlorides and reacted with arylzinc reagents. This method tolerates functional groups including aryl fluorides and chlorides, ketones, as well as N-heterocycles including pyrimidines, imidazoles, tetrazoles, and oxadiazoles. Two compounds synthesized by this method exhibited selective activity against the MCF-7 breast cancer cell line in the micromolar range. Diaryl thioethers, and particularly those containing heterocyclic moieties, are a common structural motif in natural products and medicinal agents (Figure 1). For example, thioethers have therapeutic potential for treatment of HIV,1 breast cancer,