Greening Solid-Phase Organic Synthesis: Environmentally Conscious Synthesis of Pharmaceutically Relevant Privileged Structures 5,6-Dihydropyridin-2(1 H)-ones and Quinolin-2(1 H)-ones

SCHÜTZNEROVÁ, EVA; PRIBYLKA, ADAM; MEDRAN, NOELIA S.; KRCHNÁK, VIKTOR

JOURNAL OF ORGANIC CHEMISTRY

AMER CHEMICAL SOC

Año: 2020 vol. 85 p. 11867 - 11881

0022-3263

Solid-phase organic synthesis (SPOS) is a very efficient methodology for the synthesis of diverse organic molecules, particularly exploited in drug discovery. Here, we present the transformation of the traditional SPOS to an eco-friendlier methodology on examples of pharmacologically relevant privileged structures 5,6-dihydropyridin-2(1H)-ones and quinolin-2(1H)-ones. The green approach is primarily based on the utilization of environmentally friendly solvent 2-MeTHF in all steps of the synthesis. Target heterocycles were synthesized by extending our previously published synthesis of five-membered tetramic acid analogues to six-membered cycles. The crucial step of the synthesis is cyclization via nonclassical Wittig olefination of resin-bound esters. Traditional and green protocols provided comparable results with respect to purity and yield of products, thus opening the way for greener access to a variety of diverse heterocycles.