How To Enhance the Efficiency of Breslow Intermediates for SET Catalysis.

Oxidative carbene organocatalysis, which proceeds via single electron transfer (SET) pathways, has been limited by the moderately reducing properties of deprotonated Breslow intermediates s derived from thiazol-2-ylidene and 1,2,4-triazolylidene . Using computational methods, we assess the redox potentials of s based on ten different types of known stable carbenes and report our findings concerning the key parameters influencing the steps of the catalytic cycle. From the calculated values of the first oxidation potential of s derived from carbenes to , it appears that, apart from the diamidocarbene , all the others are more reducing than thiazol-2-ylidene and the 1,2,4-triazolylidene . We observed that while the reducing power of s significantly decreases with increasing solvent polarity, the redox potential of the oxidant can increase at a greater rate, thus facilitating the reaction. The cation, associated with the base, also plays an important role when a nonpolar solvent is used; large and weakly coordinating cations such as Cs are beneficial. The radical-radical coupling step is probably the most challenging step due to both electronic and steric constraints. Based on our results, we predict that mesoionic carbene and abnormal NHC are the most promising candidates for oxidative carbene organocatalysis.