Beatriz Alonso, Marta Ocejo, Luisa Carrillo, Jose L Vicario, Efraim Reyes, Uxue Uria
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.
The Journal of organic chemistry 2013 Jan 18We 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.
Beatriz Alonso, Marta Ocejo, Luisa Carrillo, Jose L Vicario, Efraim Reyes, Uxue Uria. 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. The Journal of organic chemistry. 2013 Jan 18;78(2):614-27
PMID: 23260037
View Full Text