A Novel Strategy for the Synthesis of Trifluoroalanine Oligopeptides

Abstract

2-N-(p-Methoxyphenyl)(trimethylsilyl)aminoperfluoropropene was prepared in 95% yield by the Mg-promoted C-F bond activation in an Mg-TMSCl-DMF system. The fluorinated enamine is very electrophilic so that it reacts with a variety of α-amino esters in a triethylamine-DMF system at room temperature, affording trifluoroalanine dipeptides in 70-90% yields via one-pot process. The reaction proceeds via three steps; addition of amino group of amino esters, subsequent dehydrofluorination leading to the corresponding imidoyl fluoride, then acid-catalyzed hydrolysis of the imidoyl fluoride. The protocol is applicable for alanine tripeptides. 462