Asymmetric aldol additions catalyzed by chiral phosphoramides: Electronic effects of the aldehyde component

Abstract

The trichlorosilyl enolates of cyclopentanone and cycloheptanone were prepared by a mercury(II)-catalyzed metathesis from their TMS enol ethers in good yield. These enolates undergo spontaneous addition to aldehydes to provide the aldol adducts syn- 4, 5a-e in high yield and selectivity (dr 19 1 to > 49 1 ). More electron rich aldehydes tend to be more diastereoselective. The reaction of these enolates with aldehydes is also catalyzed by the chiral phosphoramide (S,S)- 1 to provide anti- 4, 5a-e in good to excellent diastereo- (dr 15 1 to 35 1 ) and enantioselectivity (er 84.4 15.6 to 95.9 4.1 ). In these cases, a trend is apparent only with sterically similar benzaldehyde derivatives. In addition, optimization studies suggest that two mechanistically distinct pathways may be operating in the catalyzed reaction.