Regio- and Diastereoselective Synthesis of Highly Substituted, Oxygenated Piperidines from Tetrahydropyridines

Diastereoselective
epoxidation and regioselective ring-opening
methods were developed for the synthesis of densely substituted, oxygenated
piperidines from two classes of tetrahydropyridines with distinct
stereochemical displays of functionalities. A new and practical in
situ prepared epoxidation reagent was developed for the diastereoselective
epoxidation of one class of sterically hindered tetrahydropyridines.
The novel bifunctional epoxidation reagent, 2-carboperoxy-3,4,5,6-tetrafluorobenzoic
acid, was designed to incorporate highly reactive percarboxy acid
and pendant carboxylic acid groups, which through hydrogen bonding
to the amino group successfully overrode steric effects and directed
epoxidation to occur at the more hindered face of the tetrahydropyridine.
Nucleophilic ring-opening of the epoxides with water, alcohols, and
HF proceeded with high regioselectivity, affording piperidinol products
with adjacent tetrasubstituted carbons.