title: Mild, Aqueous α-Arylation of Ketones: Towards New Diversification Tools for Halogenated Metabolites and Drug Molecules.
abstract: The palladium-catalysed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification.
authors.affiliation: EaStCHEM, School of Chemistry and BSRC, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
authors.forename: Enrico
authors.initials: E
authors.lastname: Marelli
authors.affiliation: EaStCHEM, School of Chemistry and BSRC, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Renault
authors.affiliation: EaStCHEM, School of Chemistry and BSRC, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Sharma
authors.affiliation: Chemistry Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.|Department of Inorganic and Physical Chemistry, Universiteit Gent, Krijgslaan 281-S3, 9000, Ghent, Belgium.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Nolan
authors.affiliation: EaStCHEM, School of Chemistry and BSRC, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
authors.forename: Rebecca J M
authors.identifier: http://orcid.org/0000-0001-9869-8205
authors.initials: RJ
authors.lastname: Goss
mesh_terms: D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D054879:Halogenation; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry; D011346:Prochlorperazine / Q000138:chemical synthesis / Q000737:chemistry; D014364:Tryptophan / Q000031:analogs & derivatives / Q000138:chemical synthesis
chemical_list: D014150:Antipsychotic Agents; D006841:Hydrocarbons, Aromatic; D007659:Ketones; D004364:Pharmaceutical Preparations; D010165:Palladium; D014364:Tryptophan; D011346:Prochlorperazine
keywords: amino acids; aqueous coupling; halogenated compounds; ketone arylation; palladium