Metal-free decarboxylative Hetero-Diels-Alder synthesis of 3-hydroxypyridines: A rapid access to N-fused bicyclic hydroxypiperidine scaffolds

Article abstract of DOI:10.1021/jo402729a

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.