Enantioselective acyl transfer using chiral phosphine catalysts

Early studies of kinetic resolution by Pasteur, Marckwald, Mackenzie and Dakin established that acyl transfer reactions could be used in the synthesis of enantio-enriched chiral substances. More recent work has resulted in improved enantioselectivity in kinetic resolutions using lipases, as well as non-enzymatic catalysts based on nucleophilic anhydride activation. The development of chiral, nucleophilic phosphine catalysts for this purpose is reviewed. Optimum reactivity and enantioselectivity were achieved with phosphabicyclo[3.3.0]octane (PBO) derivatives for the kinetic resolution of unsaturated benzylic or allylic alcohols. With highly hindered substrates, the enantioselectivities approach and sometimes exceed, those reported for lipase catalysts. In cases where neither the lipase nor the chiral phosphine reacts with sufficiently high selectivity, the recently developed technique of parallel kinetic resolution can give products with improved enantioselectivity This method uses two simultaneous kinetic resolutions, catalyzed by the lipase and the chiral phosphine, respectively, to afford two different products that can be easily separated. Under conditions where both enantiomeric alcohols react at similar rates, product enantiomeric purity remains nearly constant regardless of percent conversion.