Key Mechanistic Insights of Carboxylate-Assisted Carbonate-Promoted Direct C-H Carboxylation with Carbon Dioxide

A feasible synthesis route is developed for achieving the direct carboxylation of thiophene and CO2 in a relatively mild solvent-free carboxylate-assisted cesium carbonate (semi) molten state. The effects of each reaction factor on the carboxylate yield are investigated, and the phase behavior analysis of the reaction medium is detected through the thermal characterization techniques of DSC and in-situ XRD. Among these alternatively co-salt carboxylate bases, the improvement effect for carboxylation reaction changes with the variation of the assisted carboxylate salts owing to their difference in alkalinity resulting in the different deprotonation abilities. Besides, the detailed mechanism of this carboxylate-assisted carbonate-promoted carboxylation reaction is studied. It mainly consists of two consecutive steps including that the formation of carbanion represented as the organocesium is the result of base induced deprotonation and the nucleophile attacks the weak electrophile CO2 to form the C-C bond(s) in the form of cesium carboxylate. The activation energy barrier of C-H activation step is higher than the following CO2 insertion step whether for the formation of the mono- and/or di-carboxylate, which indicates that the C-H deprotonation induced by the base is slow and the resulting carbon-centered nucleophile reacts rapidly with CO2. This mechanistic insight is further validated by the base and C-H substrate effects from the experimental and computational perspectives, respectively, including the substitution of Cs and K in the mixed salt (containing K2CO3 system with auxiliary carboxylate invariable and potassium pivalate system with carbonate invariable) and the substitution of the reactant substrate of furoate and benzoate