Base-Promoted Annulative Difluoromethylenation of Enaminones with BrCF2CO2Et toward 2,2-Difluorinated 2,3-Dihydrofurans

A practical method for the synthesis of 2,2-difluorinated 2,3-dihydrofurans has been established via the [4 + 1] annulation of enaminones and BrCF2CO2Et with Na2CO3 promotion. This new protocol does not employ any transition metal reagent and enables the annulative difluoromethylation by the partial cleavage of the C=C double bond. In addition, the further treatment with hydrochloric acid in one pot leads to beta-keto enoic acids (4-oxo-2-butenoic acids) via a formal enaminone C-N carboxylation.

Automated summary

A practical method for the synthesis of 2,2-difluorinated 2,3-dihydrofurans has been developed using enaminones and BrCF2CO2Et as starting materials with Na2CO3 as the catalyst. This method does not require any transition metal reagent and enables the annulative difluoromethylation by partial cleavage of the C=C double bond. Furthermore, treatment with hydrochloric acid in the same reaction system leads to the formation of beta-keto enoic acids via formal enaminone C-N carboxylation.