Lewis Base Catalyzed Aldol Additions of Chiral Trichlorosilyl Enolates and Silyl Enol Ethers

The consequences of double diastereodifferentiation in chiral Lewis base catalyzed aldol additions
using chiral enoxysilanes derived from lactate, 3-hydroxyisobutyrate, and 3-hydroxybutyrate have
been investigated. Trichlorosilyl enolates derived from the chiral methyl and ethyl ketones were
subjected to aldolization in the presence of phosphoramides, and the intrinsic selectivity of these
enolates and the external stereoinduction from chiral catalyst were studied. In the reactions with
the lactate derived enolate, the strong internal stereoinduction dominated the stereochemical
outcome of the aldol addition. For the 3-hydroxyisobutyrate- and 3-hydroxybutyrate derived enolates,
the catalyst-controlled diastereoselectivities were observed, and the resident stereogenic centers
exerted marginal influence. The corresponding trimethylsilyl enol ethers were employed in SiCl4/bisphosphoramide catalyzed aldol additions, and the effect of double diastereodifferentiation was
also investigated. The overall diastereoselection of the process was again controlled by the strong
external influence of the catalyst.