Tandem Thioacylation‐Intramolecular Hydrosulfenylation of Propargyl Amines – Rapid Access to 2‐Aminothiazolidines

An investigation directed towards the preparation of α‐substituted propargyl thioureas from the corresponding propargylamine resulted in a tandem thioacylation/anti‐hydrosulfenylation and the formation of the corresponding thiazolidine in excellent (46–98 %) yields rather than the anticipated thiourea. Initial interpretation of this outcome was formulated in terms of the highly substituted nature of the α‐carbon of these amines resulting in steric acceleration, however, even simple propargylamines engage in this chemistry. In light of these observations, it was determined subsequently that the formation of the thiourea is quite rapid, but cyclization occurred during chromatographic purification and is in fact facilitated by silica gel. Control reactions and monitoring the progress of the reaction by NMR spectroscopy clearly indicate that the cyclization is relatively slow until either purification or the introduction of silica gel results in cyclization. Subsequently, it was found that even the parent system afforded the thiazolidine when the reaction was conducted on silica gel. Overall, the reaction is tolerant of a variety of substitution patterns, internal and terminal alkynes and isothiocyanates providing rapid access to 2‐aminothiazolidines. A metal‐free coupling reaction between propargylamines and isothiocyanates affords good yields of vinylidene substituted thiazolidines. Control reactions suggest that these reactions are in fact mediated by silica gel. A broad substrate scope and a variety of substitution patterns are accessible.