title: Modular isoquinoline synthesis using catalytic enolate arylation and in situ functionalization.
abstract: A methyl ketone, an aryl bromide, an electrophile, and ammonium chloride were combined in a four-component, three-step, and one-pot coupling procedure to furnish substituted isoquinolines in overall yields of up to 80%. This protocol utilizes the palladium catalyzed α-arylation reaction of an enolate, followed by in situ trapping with an electrophile, and aromatization with ammonium chloride. tert-Butyl cyanoacetate participated in a similar protocol; after functionalization and decarboxylation, 3-amino-4-alkyl isoquinolines were prepared in high yield.
authors.affiliation: Department of Chemistry, University of Oxford , Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, U.K., and GlaxoSmithKline , Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, U.K.
authors.forename: Ben S
authors.initials: BS
authors.lastname: Pilgrim
authors.forename: Alice E
authors.initials: AE
authors.lastname: Gatland
authors.forename: Charlie T
authors.initials: CT
authors.lastname: McTernan
authors.forename: Panayiotis A
authors.initials: PA
authors.lastname: Procopiou
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Donohoe
mesh_terms: D000643:Ammonium Chloride / Q000737:chemistry*; D002384:Catalysis; D006842:Hydrocarbons, Brominated / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D006842:Hydrocarbons, Brominated; D007546:Isoquinolines; D007659:Ketones; D000643:Ammonium Chloride; C039109:isoquinoline