Synthesis of amide-type fluoroalkene dipeptide isosteres by an intramolecular redox reaction.
We previously achieved NHC-mediated preparation of ester-type fluoroalkene dipeptide isosteres (ES-FADIs, 4) by an intramolecular redox reaction. In the present study, a cyanide ion-mediated reaction was successfully applied to the conversions of gamma,gamma-difluoro-alpha,beta-enoylsilane 1 or 2 to amide-type fluoroalkene isosteres (AM-FADIs, 5 or 6). The use of catalytic cyanide ion allowed synthesis of chiral auxiliary incorporated FADI 15b which was then subjected to a diastereoselective alpha-alkylation reaction to yield alpha-substituted FADIs 17. Furthermore, the presented amidation protocol was used for straightforward incorporation of FADI into peptidyl resin.
Yamaki
Yoko
Y
Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
Shigenaga
Akira
A
Li
Jinglan
J
Shimohigashi
Yasuyuki
Y
Otaka
Akira
A