TiCl₄-Mediated Preparation of Thiophthalide Derivatives via Formal Thio-Passerini Reactions

By the formal extension of the Passerini reaction to thiocarbonyl derivatives, the straightforward preparation of thiophthalides is disclosed. This method involves the intermediate formation of a sulfanyl-phthalide and a titanium tetrachloride mediated isocyanide insertion reaction. When tert-butyl thiol is used, thanks to the deprotection of the tert-butyl group, a thiophthalide resulting from a 1,5-Mumm rearrangement is isolated. Owing to the multifaceted activity of TiCl₄, all steps may conveniently be performed in one pot, starting directly from 2-formylbenzoic acids, tert-butyl thiol, and various isocyanides.