title: Access to 2-(Het)aryl and 2-Styryl Benzoxazoles via Palladium-Catalyzed Aminocarbonylation of Aryl and Vinyl Bromides.
abstract: A sequential one-pot procedure for the synthesis of either 2-(hetero)aryl or 2-styryl benzoxazoles is reported, starting from aryl and vinyl bromides, respectively, involving an initial aminocarbonylation with 2-aminophenols as nucleophiles followed by an acid mediated ring closure to generate the heterocycle. The methodology displays a broad substrate scope in moderate to excellent yields and can be exploited for (13)C-isotope labeling. Finally, this carbonylative protocol was applied to the synthesis of a potential Alzheimer's plaque binder and a selective PPAR antagonist including site-specific labeling with (13)C-carbon monoxide.
authors: †Center for Insoluble Protein Structures (inSPIN), Department of Chemistry and the Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.
authors: Karoline T
authors: KT
authors: Neumann
authors: ‡Interdisciplinary Nanoscience Center (iNANO), Biological and Chemical Engineering and Department of Engineering, Aarhus University, Finlandsgade 22, 8200 Aarhus N, Denmark.
authors: Anders T
authors: AT
authors: Lindhardt
authors: §Lundbeck Research Denmark, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark.
authors: Benny
authors: B
authors: Bang-Andersen
authors: †Center for Insoluble Protein Structures (inSPIN), Department of Chemistry and the Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.
authors: Troels
authors: T
authors: Skrydstrup
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000627:Aminophenols; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002248:Carbon Monoxide / Q000737:chemistry; D002384:Catalysis; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D047492:Peroxisome Proliferator-Activated Receptors / Q000037:antagonists & inhibitors*; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D000627:Aminophenols; D001583:Benzoxazoles; D006842:Hydrocarbons, Brominated; C520139:JTP-426467; D047492:Peroxisome Proliferator-Activated Receptors; D013343:Styrenes; D014753:Vinyl Compounds; C027667:2-aminophenol; D010165:Palladium; D002248:Carbon Monoxide; C003763:vinyl bromide