title: Efficient synthesis of trifluoromethyl and related trisubstituted alkene dipeptide isosteres by palladium-catalyzed carbonylation of amino acid derived allylic carbonates.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Inokuchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Narumi
authors.forename: Ayumu
authors.initials: A
authors.lastname: Niida
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tomita
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohno
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
mesh_terms: 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
chemical_list: D000475:Alkenes; D000596:Amino Acids; D002254:Carbonates; D004151:Dipeptides; D006845:Hydrocarbons, Fluorinated; D010165:Palladium