title: Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S,S)-(+)-pseudoephedrine as chiral auxiliary; enantioselective synthesis of 3-substituted pyrrolidines.
abstract: We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.
authors.affiliation: Departamento de Química Orgánica II, Facultad de Ciencia y Tecnología, Universidad del País Vasco/Euskal Herriko Unibertsitatea UPV/EHU, P.O. Box 644, E-48080 Bilbao, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alonso
authors.forename: Marta
authors.initials: M
authors.lastname: Ocejo
authors.forename: Luisa
authors.initials: L
authors.lastname: Carrillo
authors.forename: Jose L
authors.initials: JL
authors.lastname: Vicario
authors.forename: Efraim
authors.initials: E
authors.lastname: Reyes
authors.forename: Uxue
authors.initials: U
authors.lastname: Uria
mesh_terms: D000586:Amination; D000838:Anions / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D018020:Lithium Compounds / Q000737:chemistry*; D015394:Molecular Structure; D054199:Pseudoephedrine / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000838:Anions; D007202:Indicators and Reagents; D018020:Lithium Compounds; D011759:Pyrrolidines; D054199:Pseudoephedrine; D008094:Lithium