Metal-Free Radical [3 + 2] Annulation of Tetraalkylthiuram Disulfide with Alkynes/Alkenes: an Approach of Synthesizing 1,3-Dithiole and 1,3-Ditholane Derivatives

A novel and metal-free [3 + 2] annulation of tetraalkylthiuram disulfide with alkynes/alkenes has been developed using Selectfluor at room temperature. The formed 1,3-dithiol-2-ylium/1,3-dithiolan-2-ylium salts can be easily transformed into the corresponding 1,3-dithiol-2-ylidenes/1,3-ditholan-2-ylidenes by one-pot subsequent condensation with malononitrile. The present protocol features the use of easily accessible starting materials, mild reaction conditions, good tolerance with diverse functional groups, easy scale-up, and a wide substrate scope, affording the desired products in good yields. Importantly, this method is suitable for the late-stage modification of bioactive molecules. Furthermore, 1,3-dithiol-2-ylium salt can also be easily converted into various 1,3-dithiole derivatives by condensation, reduction, or hydrolysis. Mechanism studies show that this transformation involves radical annulation. Of note, this method presented a novel example using tetraalkylthiuram disulfide as a sulfur synthon in annulation, which greatly enriches the application of tetraalkylthiuram disulfides in organic synthesis. Biological evaluation indicates that these prepared compounds are promising candidates in terms of their antitumor activity.