Enantioselective construction of quaternary stereogenic carbon atoms by the lewis base catalyzed additions of silyl ketene imines to aldehydes

Silyl ketene imines derived from a variety of α-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers via the aldol addition reaction. In the presence of SiCl₄ and the catalytic action of a chiral phosphoramide, silyl ketene imines undergo extremely rapid and high yielding addition to a wide variety of aromatic aldehydes with excellent diastereo- and enantioselectivity. Of particular note are the high yields and selectivities obtained from electron-rich, electron-poor, and hindered aldehydes. Linear aliphatic aldehydes did react with good diastereo- and enantioselectivity in the presence of nBu₄N⁺I^-, but branched aldehydes were much less reactive. Semiempirical calculations provided a rationalization of the observed diastereo- and enantioselectivity via open transitions states. From Si to C: Silyl ketene imines derived from a variety of α-branched nitriles have been developed as highly useful reagents for the construction of quaternary stereogenic centers through the aldol addition reaction. In the presence of SiCl₄ and catalytic amounts of a chiral Lewis base (LB), silyl ketene imines undergo highly selective additions to a variety of aromatic and aliphatic aldehydes (see scheme).