The potential of carbon dioxide in synthetic organic chemistry

The aim of this review is to demonstrate, using examples developed in our own laboratories, that carbon dioxide has real potential in synthetic organic process chemistry. As well as potential environmental benefits, it offers opportunities for enhanced diastereo- and enantioselectivity compared to processes in conventional solvents. Fine control of reagent and product solubilities can lead to selective product separation and novel CO2-induced reactions. Pd-mediated cross-coupling reactions in scCO(2) can give increased yields and selectivities, especially in the presence of usually incompatible functionality such as amines, which are protected in situ by reaction with CO2. Useful reactions can also be carried out at subcritical pressures utilising either the Lewis acidity of CO2 or the Bronsted acidity of carbonic acid formed in aqueous solutions under an atmosphere of CO2. Finally, product processing (extraction, chromatography, crystallisation) can also be carried out using CO2 without significant amounts of conventional solvents. We believe that the principles demonstrated here can be applied to a wide variety of procedures of relevance to organic process chemistry, and that the use of scCO(2) as a solvent, whilst currently in its infancy in this area, will be of increasing importance in the future.