DOI: 10.1021/acs.joc.6c01845 ISSN: 0022-3263
Defluorinative [3 + 3] Annulation Reaction of α -Fluoroacetamides with 2-Trifluoromethylalkenes for the Formation of Densely Functionalized Difluorinated δ
Sanoop P. Chandrasekharan, Usha Yadav, Indrajith K. Biju, Shreeya Srivastava, Kishor MohananAbstract
The work reported herein details a generalized [3 + 3] annulation approach for the construction of an important class of difluorinated δ-lactam motifs using α-fluoroacetamides and 2-CF3-1,3-enynes. The key to this advancement lies in the strategic use of α-fluoro-β-ketoamide as a 1,3-binucleophilic synthon and 2-CF3-1,3-enyne as a 1,3-dielectrophilic species. Mechanistically, the reaction proceeds through a sequential nucleophilic substitution of an allylic fluorine atom (SN2′) followed by a ring-closing nucleophilic vinylic fluorine atom substitution (SNV) cascade, involving α-fluoroacetamides and CF3-enynes. Moreover, we successfully leveraged α-fluoromalonamates as a useful 1,3-binucleophilic synthon in place of α-fluoroacetamides.