Efficient synthesis of trifluoromethyl and related trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation of amino acid derived allylic carbonates

Article abstract of DOI:10.1021/jo702318d

(Chemical Equation Presented) A novel stereoselective synthetic approach to (Z)-trifluoromethylalkene dipeptide isosteres (CF₃-ADIs) is described. Starting from readily available N-Boc-L-phenylalanine, Phe-Gly type CF₃-ADIs were obtained through palladium-catalyzed carbonylation of allylic carbonates under CO. While the reaction of N-Boc derivatives proceeds in excellent yields but lower stereoselectivity (E:Z = 62:38-43:57), the reaction of the N,N-diBoc derivative exclusively affords the desired (Z)-isomer in 61% yield. We also present a highly stereoselective synthesis of several Phe-Gly type trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation.