Dissecting competitive mechanisms: thionation vs. cycloaddition in the reaction of thioisomu?nchnones with isothiocyanates under microwave irradiation

Cantillo, David, Ávalos, Martín, Babiano, Reyes, Cintas, Pedro, Jiménez, José L., Light, Mark E. and Palacios, Juan C. (2009) Dissecting competitive mechanisms: thionation vs. cycloaddition in the reaction of thioisomu?nchnones with isothiocyanates under microwave irradiation. Journal of Organic Chemistry, 74 (20), 7644-7650. (doi:10.1021/jo900960a).

Abstract

This paper documents in detail the reaction of 1,3-thiazolium-4-olates (thioisomnchnones) with aryl isothiocyanates. Having demonstrated with a chiral model that thionation occurs under these conditions to provide 1,3-thiazolium-4-thiolates and that this process is actually a stepwise domino reaction (J. Org. Chem. 2009, 74, 3698?3705), we extend this study to monocyclic thioisomnchnones. Herein, competition between thionation and 1,3-dipolar cycloaddition takes place. The process is synthetically disappointing at room temperature requiring prolonged reaction times for completion. The protocol has been subsequently investigated by using both microwave dielectric heating and conventional thermal heating (oil bath) in DMF at 100 °C with an accurate internal reaction temperature measurement. Although a slight acceleration was observed for reactions conducted under microwave irradiation, for most cases the observed yields and chemoselectivities were quite similar. Thus one can conclude that, within experimental errors, the reactivity is not related to nonthermal effects in agreement with recent reassessments on this subject, particularly by Kappe and associates (J. Org. Chem. 2008, 73, 36; J. Org. Chem. 2009, 74, 6157). The whole reaction system, which includes numerous heavy atoms, can be computationally modeled with a hybrid ONIOM[B3LYP/6-31G(d):PM3] level. This reproduces well experimental results and suggests a sequential mechanism. To further corroborate the nonconcertedness, the potential energy surface (PES) has been constructed for simplified models, locating the corresponding stationary points. In doing so, we introduce for the first time a useful and convenient mathematical protocol to locate the stationary points along a reaction path. The protocol is quite simple and should convince many organic chemists that certain daunting theoretical treatments can be made easy

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Contributors

Author: Mark E. Light

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