Metal-Free Decarboxylative Hetero-Diels-Alder Synthesis of 3-Hydroxypyridines: A Rapid Access to N-Fused Bicyclic Hydroxypiperidine Scaffolds

摘要

A complete experimental and theoretical study of the thermally controlled metal-free decarboxylative hetero-Diels-Alder (HDA) reaction of 5- alkoxyoxazoles with acrylic acid is reported. This strategy offers a new entry to valuable 2,6-difunctionalized 3-hydroxypyridines from readily available 2- and 4- disubstituted 5-alkoxyoxazoles. The reaction conditions proved compatible with, among others, ketone, amide, ester, ether, and nitrile groups. The broad functional group tolerance of the protocol allows a rapid and versatile access to both hydroxyindolizidine and hydroxyquinolizidine derivatives via a pyridine dearomatization strategy.