161. P. Müller, P. Nury, G. Bernardinelli,
     “Asymmetric Nucleophilic Substitution of Acetals”
     Eur. J. Org. Chem. 2001, 4137-4147.

Benzaldehyde dimethylacetal (1) and 2-aryl-1,3-dioxolanes 5 react with organolithium reagents 2 in the presence of chiral ligands such as sparteine (3), 1-alkoxy-2-aminoethanes, or 1,2-dialkoxyethanes and BF₃ to afford monosubstitution products in high yields and in up to 81% enantiomeric excess. The 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-dioxolane (5c) on treatment with 2-ethylphenyllithium (2i) in the presence of sparteine. The approach was applied to the synthesis of enantioenriched (S)-(-)-neobenodine (17) with 49% ee.

DOI : 10.1002/1099-0690(200111)2001:21<4137::AID-EJOC4137>3.0.CO;2-4