ABSTRACT
Department of Chemistry, University of California, Davis, California, U.S.A.
Synthesis of chiral pharmaceuticals with catalyst recovery and enhanced rate and selectivity is possible, for some reactions, with the use of liquid or supercritical CO2 as a substitute for traditional organic solvents. Supercritical CO2 (scCO2) is an appropriate medium for the synthesis of pharmaceuticals because it is nontoxic, unlikely to be left in the product, relatively inert, inexpensive, and environmentally benign. Because of its unusual physical properties, it can also cause higher rates for certain reactions involving reagent gases. Improved selectivities have also been observed for some syntheses. Supercritical CO2 and other supercritical fluids (SCFs) are used industrially as solvents for several reactions (1) but not yet for pharmaceutical synthesis. This chapter will describe the potential that SCFs and especially scCO2 have for asymmetric catalysis in the pharmaceutical industry, starting with a description of general aspects of reactions in SCFs, a survey of reports of asymmetric synthesis using catalysts in SCFs, a summary of related techniques, and a discussion of the outlook. The studies described herein show definitively that the advantages of SCFs are significant and realizable for asymmetric syntheses of practical importance. It remains up to the pharmaceutical industry to decide whether to take advantage of these discoveries.
