Synthesis of fluoroalkene dipeptide isosteres by an intramolecular redox reaction utilizing N-heteorocyclic carbenes (NHCs).

(Z)-Fluoroalkene dipeptide isosteres (FADIs 16) have served as potential dipeptide mimetics possessing the substitution of fluoroalkenes for parent peptide bonds. Previously, we synthesized FADIs by reduction of gamma,gamma-difluoro-alpha,beta-enoates with organocoppers or SmI(2), which prompted us to use an intramolecular redox reaction mediated by N-heterocyclic carbenes (NHCs) for the preparation of FADIs. Instead of the enoates, gamma,gamma-difluoro-alpha,beta-enal 20 and gamma,gamma-difluoro-alpha,beta-enoylsilane 34 were converted to FADIs by an NHC-mediated intramolecular redox reaction, whereby aldehyde components reduced the allylic difluoride component in an S(N)2' manner with accompanying monodefluorination.