Unveiling the reactivity of CO2 with carbanions: a theoretical analysis of the carboxylation step

The synthetic insertion of carbon dioxide into organic scaffolds typically requires the reaction of CO2 with a carbanion (carboxylation step), with the latter being generated through chemical, electrochemical, or photochemical routes. Still, little is known about the energetic and structural requirements of this step. In this work, we unveil the reactivity of CO2 with a selected set of 28 carbanions through DFT calculations and provide linear free-energy relationships that correlate the Delta G(0) and the Delta G double dagger of the carboxylation step. These reveal a Leffler-Hammond parameter alpha = 0.26 +/- 0.02 and an intrinsic barrier Delta G double dagger(0) = 12.7 +/- 0.3 kcal mol(-1) (omega b97XD/aug-cc-pvtz//omega b97XD/def2tzvp level of theory), indicative of smooth reactivity of carbanions with CO2. This reactivity is further associated with the basicity of the carbanions (expressed as the pK(aH) of the conjugate acid), in a linear Br & oslash;nsted plot between calculated Delta G double dagger and experimental pK(aH) (slope beta = 0.40 +/- 0.04 kcal mol(-1)). According to the Mayr-Patz equation, calculations allow the extrapolation of electrophilicity values for CO2 in the range from -15.3 to -18.7, in good agreement with a single reported experimental value of -16.3. Concerning the structural changes occurring in the transition state, the major energy penalty comes from the distortion of CO2. These findings can be useful in designing novel reactivity targeting carbon dioxide fixation.