Switching the Stereochemical Outcome of 6-Endo-Trig Cyclizations; Synthesis of 2,6-Cis-6-Substituted 4?Oxopipecolic Acids

摘要

A base-mediated 6-endo-trig cyclization ofnreadily accessible enone-derived α-amino acids has beenndeveloped for the direct synthesis of novel 2,6-cis-6-nsubstituted-4-oxo-L-pipecolic acids. A range of aliphatic andnaryl side chains were tolerated by this mild procedure to giventhe target compounds in good overall yields. Molecularnmodeling of the 6-endo-trig cyclization allowed some insight asnto how these compounds were formed, with the enolatenintermediate generated via an equilibrium process, followed by irreversible tautomerizationeutralization providing the drivingnforce for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolicnacids to the corresponding 4-hydroxy-L-pipecolic acids was also performed.