Efficient Synthesis of 2-Aryl-4H-pyrano[2,3-b]pyridine-4-ones

Significance

The surprise that the synthesis of 2-aryl-4H-pyrano[2,3-b]pyridine-4-ones proceeded in low yields using conventional methods for the classical Pechmann and Knoevenagel-type condensations prompted an exploration of alternatives, the results of which are reported here. In the presence of pyridinium hydrochloride the propane-1,3-diones A underwent cyclization and deprotection to give coumarones when heated to 190 ˚C for 1-4 hours in poor to good yields. Groups such as OMe, OBn, OTBS, and NHBoc undergo cleavage under the reaction conditions to afford the corresponding parent alcohol or amine. It was possible to stop the reaction prior to cleavage taking place, but this required careful reaction monitoring on a case-by-case basis. The substrate scope was well studied and the starting materials are readily available from substituted ­acetophenones and 2-alkoxynicotinates.