Selective defluorination approach to N-Cbz-3,3-difluoro-2-difluoromethylenepyrrolidine and its application to 3,3-difluoroproline dipeptide synthesis.
Mg-promoted defluorination of N-(p-methoxyphenyl)bis(trifluoromethyl)imine 1 gave perfluoroenamine 2, which was readily transformed to N-Cbz-2-trifluoromethyl-3,3-difluoropyrrolidine 10. Chemoselective defluorination from the trifluoromethyl group of 10 by LHMDS-promoted dehydrofluorination in THF provided 3,3-difluoro-2-difluoromethylenepyrrolidine 11. The product 11 was converted to 3,3-difluoroproline dipeptides 16 upon treatment with aminoesters.
Guo
Yong
Y
Department of Applied Chemistry, Faculty of Engineering, Okayama University, 3-3-1 Tsushima-naka, Okayama, 700-8530 Japan.
Fujiwara
Kana
K
Amii
Hideki
H
Uneyama
Kenji
K
D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D004151:Dipeptides; D006845:Hydrocarbons, Fluorinated; D011759:Pyrrolidines; D011392:Proline