title: Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles.
abstract: Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium-catalyzed cross-coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine-protein kinase STK10 were synthesized.
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, M5S 3H6, Canada.
authors.forename: C Frank
authors.initials: CF
authors.lastname: Lee
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, M5S 3H6, Canada.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Holownia
authors.affiliation: Structural Genomics Consortium (SGC), Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Bennett
authors.affiliation: Structural Genomics Consortium (SGC), Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Elkins
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, M5S 3H6, Canada.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: St Denis
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, M5S 3H6, Canada.
authors.forename: Shinya
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George St., Toronto, ON, M5S 3H6, Canada.
authors.forename: Andrei K
authors.identifier: 0000-0003-3170-9103
authors.initials: AK
authors.lastname: Yudin
mesh_terms: D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D007093:Imidazoles / Q000138:chemical synthesis*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001897:Boronic Acids; D007093:Imidazoles; D010165:Palladium
keywords: biological activity; boron; cross-coupling; heterocycles; synthetic methods