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

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.