Synthesis of 4-Pyrones by Formal Hydration of 1,3-Diynones Promoted by 1,4-Addition of Piperidine

A new approach for the synthesis of 4-pyrones with broader substrate scope and functional group tolerance is described. The reaction proceeds via an initial 1,4-addition by piperidine, followed by nitrogen-assisted 6-endo-dig cyclization and hydrolysis. 1,3-Diynones with nonenolizable electron-withdrawing ketones and nonpropargylic H provide relatively high yields. For substrates with particular R-2 substituents, 1,4-or 1,6-adducts were isolated, suggesting that steric and electronic factors of the R-2 substituent should have a strong impact on the 6-endo-dig cyclization.

Automated summary

A new approach for the synthesis of 4-pyrones with broader substrate scope and functional group tolerance is described in this study. The reaction involves the 1,4-addition by piperidine, followed by nitrogen-assisted 6-endo-dig cyclization and hydrolysis. It is found that 1,3-diynones with nonenolizable electron-withdrawing ketones and nonpropargylic H provide high yields. The presence of particular R-2 substituents resulted in the isolation of 1,4-or 1,6-adducts, indicating the strong impact of steric and electronic factors on the 6-endo-dig cyclization.