carboxylations

Carboxylation is a chemical transformation in which a carboxyl group (-COOH) is introduced into a molecule, most commonly by reaction with carbon dioxide (CO2). In organic synthesis, carboxylations expand carbon skeletons and enable the preparation of carboxylic acids and their derivatives. In biochemistry, carboxylation refers to enzyme-catalyzed additions of CO2 to substrates, essential in metabolism and photosynthesis.

Chemical carboxylation methods include direct reactions with CO2, though CO2 is a relatively weak electrophile and such processes often require bases, elevated pressures, or catalysts. Traditional examples include the reaction of Grignard reagents or organolithium compounds with CO2 to yield carboxylic acids after aqueous workup. The Kolbe–Schmitt reaction is a classic industrial example, where phenoxide reacts with CO2 under high pressure to give salicylic acid after acid workup. Modern approaches employ transition-metal catalysts to promote carboxylation of alkenes, arenes, or aryl halides with CO2, producing carboxylate or carboxylic acid products under milder conditions. These methods are actively explored for sustainable CO2 utilization and carbon–carbon bond construction.

Biological carboxylation plays a central role in metabolism. In photosynthesis, the enzyme RuBisCO fixes CO2 by carboxylating ribulose-1,5-bisphosphate to form two molecules of 3-phosphoglycerate, incorporating inorganic carbon into organic matter. In cellular metabolism, pyruvate carboxylase catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, using biotin as a cofactor. These enzymatic carboxylations are examples of anaplerotic reactions that replenish intermediate pools in metabolic networks.

Overall, carboxylation encompasses a range of reactions that introduce a carboxyl group via CO2, with significant applications in synthesis, metabolism, and efforts toward CO2 utilization.