Chiral phosphoramide-catalyzed aldol additions of ketone enolates. Preparative aspects

Trichlorosilyl enolates of ketones (enoxytrichlorosilanes) were demonstrate d to be highly reactive aldol addition reagents. Trichlorosilyl enolates of cyclohexanone (E-enolate) and propiophenone (Z-enolate) reacted readily at room temperature with a wide variety of aldehydes to afford aldol addition products in high yield and diastereoselectivity (E --> syn, Z --> anti). T hese reactions were shown to be highly susceptible to acceleration by catal ytic quantities of chiral phosphoramides. In particular, a phosphoramide de rived from (S,S)-stilbenediamine was remarkably effective not only in accel erating the reaction but also in modulating the diastereoselectivity and in providing the aldol addition products in good to excellent enantioselectiv ity. The diastereoselectivity of the unpromoted process has been interprete d as a consequence of reaction via a pentacoordinate, trigonal bipyramidal (tbp) silicon complex through a boatlike transition structure. The phosphor amide-catalyzed reactions are more complicated and are believed to proceed via hexacoordinate, octahedral complexes through chairlike transition struc tures. A systematic examination of the influence of solvent, concentration, addition rate, and catalyst loading on rate and stereoselectivity is also described.