34 research outputs found
Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids
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