Synthesis of novel α-CF3-trifluoroalanine derivatives containing N-(diethoxyphosphoryl)difluoroacetyl group

An efficient synthesis of biologically interesting α-CF3-trifluoroalanine derivatives bearing N-(diethoxyphosphoryl)difluoroacetyl moiety in good yields has been elaborated. The key substrate, α-TFM-imino ester, prepared from methyl trifluoropyruvate and (diethoxyphosphoryl)difluoroacetamide, followed by dehydration, was subjected to regiospecific reactions with various nucleophiles, including organometallic, π-donor compounds and sodium borohydride. These novel products may find a viable application in the modification of peptides or serve as potential drug candidates.

Graphical abstractAn efficient synthesis of biologically interesting α-CF3-trifluoroalanine derivatives bearing N-(β-keto-α,α-difluoromethylenephosphonate) moiety in good yields has been described.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights▶ Methyl trifluoropyruvate and (diethoxyphosphoryl)difluoroacetamide. ▶ Novel acyl imine with N-(diethoxyphosphoryl)difluoroacetyl. ▶ Trifluoroalanine derivatives with a N-(diethoxyphosphoryl)difluoroacetyl function. ▶ Alkylation and arylation of the acylimine. ▶ Friedel-Crafts electrophilic aminoalkylation of π-rich aromatics and heteroaromatics.