title: Three-component coupling approach for the synthesis of diverse heterocycles utilizing reactive nitrilium trapping.
abstract: The formation of an unexpected heterocyclic scaffold, a benzoxazole, in a three-component reaction between a ketone, isocyanide, and 2-aminophenol was encountered. This reaction involved a benzo[b][1,4]oxazine intermediate resulting from intramolecular attack of the aminophenol hydroxyl group on the nitrilium ion. Unlike previous literature examples, the trapped nitrilium benzo[b][1,4]oxazine could readily be subjected to ring opening with bis-nucleophiles. The reaction scope includes simple linear as well as complex cyclic ketones and substituted 2-aminophenols. A representative benzoxazole product could be further diversified to yield drug-like compounds.
authors.affiliation: Department of Neurology, Memorial Sloan Kettering Cancer Center , 1275 York Avenue, New York, New York 10065, United States.
authors.forename: András
authors.initials: A
authors.lastname: Váradi
authors.forename: Travis C
authors.initials: TC
authors.lastname: Palmer
authors.forename: Paula R
authors.initials: PR
authors.lastname: Notis
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Redel-Traub
authors.forename: Daniel
authors.initials: D
authors.lastname: Afonin
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Subrath
authors.forename: Gavril W
authors.initials: GW
authors.lastname: Pasternak
authors.forename: Chunhua
authors.initials: C
authors.lastname: Hu
authors.forename: Indrajeet
authors.initials: I
authors.lastname: Sharma
authors.forename: Susruta
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000627:Aminophenols / Q000737:chemistry*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D010078:Oxazines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000627:Aminophenols; D001583:Benzoxazoles; D007659:Ketones; D009570:Nitriles; D010078:Oxazines; C027667:2-aminophenol