Metal-Free Decarboxylative Hetero-Diels–Alder Synthesis of 3‑Hydroxypyridines: A Rapid Access to N‑Fused Bicyclic Hydroxypiperidine Scaffolds
journal contributionposted on 07.02.2014, 00:00 by Laurie-Anne Jouanno, Vincent Di Mascio, Vincent Tognetti, Laurent Joubert, Cyrille Sabot, Pierre-Yves Renard
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.
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reaction conditionspyridine dearomatization strategynitrile groupsHDADecarboxylativeetherhydroxypyridinegroup toleranceRapid AccessaccessesterdecarboxylativehydroxyindolizidineSynthesiHydroxypyridineHydroxypiperidineScaffoldsAacrylic acidBicyclicamidedifunctionalizeddisubstitutedhydroxyquinolizidine derivativesketoneentryotheralkoxyoxazole