Asymmetric nucleophilic substitution of acetals

Benzaldehyde dimethylacetal (1) and 2-aryl-1,3-dioxolanes 5 react with orga nolithium reagents 2 in the presence of chiral ligands such as sparteine (3 ), 1-alkoxy-2-aminoethanes, or 1,2-dialkoxyethanes and BF3 to afford monosu bstituticn products in high yields and in up to 81% enantiomeric excess. Th e enantioselectivity is strongly influenced by steric effects in the acetal and in the reagent. The highest ee was achieved with 2-(2-isopropyl)-1,3-d ioxolane (5c) on treatment with 2-ethylphenyllithium (2i) in the presence o f sparteine. The approach was applied to the synthesis of enantioenriched ( S)-(-)-neobenodine (17) with 49% ee.