The Tale of Two Aminophosphines: Exploiting the Ramirez Mechanism to Access Difluoroenolate Chemistry using Trifluoromethyl ketones

Abstract

Selective aliphatic C-F bond cleavage of trifluoromethyl ketones mediated bytris(dialkylamino)phosphines are explored to access difluoroenolate chemistry. Two aminophosphines derivatives are investigated: P(NMeCH2CH2)3N (me-VB) and P(NEt2)3. The me-VB/B(C6H5)3 FLP reacts with 2,2,2-trifluoroacetophenone to generate difluoroalkenyl phosphatrane (DFEP). The azaphosphatrane structure disallowed access to difluoroenolate chemistry under mild conditions. Difluoroenolate chemistry was accessed when reacting me-VB with 2,2,2-trifluoroacetophenone in the absence of B(C6H5)3 to generate the aldol-homoadduct product. Switching the aminophosphine to P(NEt2)3 enabled the formation of difluoroalkenyl phosphonium (DFEPn3) when reacting with 2,2,2-trifluoroacetophenone in the presence of B(C6H5)3. The acyclic phosphonium character of DFEPn3 enabled facile access to difluoroenolate chemistry using fluoride or hydroxide as the nucleophile. The first example of converting 2,2,2-trifluoroacetophenone to 2,2-difluoroacetophenone at room temperature using main-group compounds is reported.