A CO2-Catalyzed Transamidation Reaction

Amide bond formation reactions are often mediated by reactive substrates in the presence of over-stoichiometric activating reagents and/or catalysts. Here we report a CO2-promoted transamidation reaction without additive metal catalysts or coupling reagents. The reaction forms byproducts, ammonia, primary and secondary amines, which can form adducts with CO2, thereby shifting the equilibrium in the desired direction. A comparison of Hammett studies under CO2 and N2 atmospheres suggests that the reaction transition state can be stabilized by electrophilic CO2. Selective modification of peptides was demonstrated, showing that CO2 can be utilized to control the nature of the electrophilicity and nucleophilicity of reaction partners under practical reaction conditions.