title: General method for the preparation of active esters by palladium-catalyzed alkoxycarbonylation of aryl bromides.
abstract: A useful method was developed for the synthesis of active esters by palladium-catalyzed alkoxycarbonylation of (hetero)aromatic bromides. The protocol was general for a range of oxygen nucleophiles including N-hydroxysuccinimide (NHS), pentafluorophenol (PFP), hexafluoroisopropyl alcohol (HFP), 4-nitrophenol, and N-hydroxyphthalimide. A high functional group tolerance was displayed, and several active esters were prepared with good to excellent isolated yields. The protocol was extended to access an important synthetic precursor to the HIV-protease inhibitor, saquinavir, by formation of an NHS ester followed by acyl substitution.
authors.affiliation: The Center for Insoluble Protein Structures (inSPIN), Department of Chemistry and the Interdisciplinary Nanoscience Center, Aarhus University , Gustav Wieds Vej 14, 8000 Aarhus, Denmark.
authors.forename: Angelina M
authors.initials: AM
authors.lastname: de Almeida
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Andersen
authors.forename: Anders T
authors.initials: AT
authors.lastname: Lindhardt
authors.forename: Mauro V
authors.initials: MV
authors.lastname: de Almeida
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup
mesh_terms: D001965:Bromides / Q000737:chemistry*; D002384:Catalysis; D004952:Esters; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D010797:Phthalimides / Q000737:chemistry*; D019258:Saquinavir / Q000138:chemical synthesis* / Q000737:chemistry*; D013388:Succinimides / Q000737:chemistry*
chemical_list: D001965:Bromides; D004952:Esters; D017320:HIV Protease Inhibitors; D006846:Hydrocarbons, Halogenated; D010797:Phthalimides; D013388:Succinimides; D010165:Palladium; C037437:N-hydroxyphthalimide; D019258:Saquinavir; C001426:N-hydroxysuccinimide