Efficient synthesis of trifluoromethyl and related trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation of amino acid derived allylic carbonates.
A novel stereoselective synthetic approach to (Z)-trifluoromethylalkene dipeptide isosteres (CF(3)-ADIs) is described. Starting from readily available N-Boc-L-phenylalanine, Phe-Gly type CF(3)-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.
Inokuchi
Eriko
E
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Narumi
Tetsuo
T
Niida
Ayumu
A
Kobayashi
Kazuya
K
Tomita
Kenji
K
Oishi
Shinya
S
Ohno
Hiroaki
H
Fujii
Nobutaka
N
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry*; D002254:Carbonates / Q000737:chemistry*; D002384:Catalysis; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
D000475:Alkenes; D000596:Amino Acids; D002254:Carbonates; D004151:Dipeptides; D006845:Hydrocarbons, Fluorinated; D010165:Palladium