Mechanochemical Activation of NaHCO₃: A Solid CO₂ Surrogate in Carboxylation Reactions

Carbon dioxide, a primary driver of global warming, offers a promising feedstock for valuable chemical synthesis. Nonetheless, the reliance on highly pressurized canisters and specialized equipment limits its practical application in fine chemical synthesis. This study explores the innovative use of sodium bicarbonate (NaHCO₃) as a safe, solid, on-demand source of CO₂ under mechanochemical conditions to perform carboxylation reactions. Two applications of the practical mechanochemical syntheses using sodium bicarbonate are developed: first, the synthesis of cyclic carbamates from propargylic amines is investigated, and second, cyclic organic carbonates are derived from epoxides. The potential of this approach in the pharmaceutical industry is further showcased by demonstrating the solvent-minimized synthesis of pharmaceutically relevant molecules and introducing a ¹³C-labeling strategy utilizing NaH¹³CO₃.