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Asymmetric Nucleophilic Substitution of Acetals
Author(s) -
Müller Paul,
Nury Patrice,
Bernardinelli Gérald
Publication year - 2001
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200111)2001:21<4137::aid-ejoc4137>3.0.co;2-4
Subject(s) - chemistry , acetal , sparteine , reagent , benzaldehyde , nucleophilic substitution , dioxolane , steric effects , enantiomer , enantioselective synthesis , aryl , alkoxy group , medicinal chemistry , enantiomeric excess , substitution reaction , stereochemistry , organic chemistry , catalysis , alkyl
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 BF 3 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 .