Organocatalytic Asymmetric Conjugate Addition to Allenic Esters and Ketones

The first example of an organocatalytic enantioselective conjugate addition of cyclic β-ketoesters
and glycine imine derivatives to electron-deficient allenes is described. We disclose that the corresponding
chiral β,γ-unsaturated carbonyl compounds are formed exclusively under phase-transfer conditions using
either cinchona-alkaloid-derived or biphenyl-based chiral quaternary ammonium salts as catalysts. The
scope of the reaction for β-ketoesters is outlined for allenes having a ketone or ester motif as electron-withdrawing group as well as different substituents in the 3-position, giving the optically active products in
high yields and excellent diastereo- and enantioselectivities (90−96% ee). The conjugate addition also
proceeds for a number of cyclic β-ketoesters having different ring sizes, ring systems, and substituents in
high yields and enantioselectivities. Glycine imine derivatives also undergo the asymmetric conjugate addition
to electron-deficient allenes in high yields and with enantioselectivities in the range of 60−88% ee, thus
providing a rapid entry to optically active α-vinyl-substituted α-amino acid derivatives. It is shown that the
enantioselectivity is strongly dependent on the size of the ester moiety of the nucleophile in combination
with the catalytic system used. The high synthetic value of the chiral products arising from these new
catalytic processes is demonstrated by two straightforward transformations leading in one case to optically
active hexahydrobenzopyranones and in the other to substituted pyroglutamates (γ-lactames).