title: Switching the stereochemical outcome of 6-endo-trig cyclizations; synthesis of 2,6-cis-6-substituted 4-oxopipecolic acids.
abstract: A base-mediated 6-endo-trig cyclization of readily accessible enone-derived α-amino acids has been developed for the direct synthesis of novel 2,6-cis-6-substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains were tolerated by this mild procedure to give the target compounds in good overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some insight as to how these compounds were formed, with the enolate intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-l-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed.
authors.affiliation: WestCHEM, School of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Daly
authors.forename: Alastair A
authors.initials: AA
authors.lastname: Cant
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Fowler
authors.forename: Graham L
authors.initials: GL
authors.lastname: Simpson
authors.forename: Hans Martin
authors.initials: HM
authors.lastname: Senn
authors.forename: Andrew
authors.initials: A
authors.lastname: Sutherland
mesh_terms: D003500:Cyclization; D015394:Molecular Structure; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D010875:Pipecolic Acids