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.
The hydrogen bonding-directed sequential 1,6/1,4-additions developed herein allow for creating unique heterocycles with structural diversity under mild conditions without using metal catalysts or organometallic reagents.
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