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

Abstract

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 ΔG⁰ and the ΔG^‡ of the carboxylation step. These reveal a Leffler–Hammond parameter α = 0.26 ± 0.02 and an intrinsic barrier ΔG^‡₀ = 12.7 ± 0.3 kcal mol⁻¹ (ωb97XD/aug-cc-pvtz//ωb97XD/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 Brønsted plot between calculated ΔG^‡ and experimental pK_aH (slope β = 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.