title: Regioselective Bromination of Benzocycloheptadienones for the Synthesis of Substituted 3,4-Benzotropolones Including Goupiolone A.
abstract: Type-18 or -23 benzocycloheptadienones are readily prepared by ring-closing olefin metatheses. Adding Br2to 23 and eliminating HBr gave the bromoolefin 28 using DBU or its isomer iso-28 using DABCO, both with near-perfect regiocontrol. Both 28 and iso-28 underwent Sonogashira, Suzuki, Negishi, and Heck couplings as well as Pd-catalyzed alkoxycarbonylations. Hydrolysis of the resulting α-ketoketals and enolization of the liberated α-diketones delivered a portfolio of hitherto unknown 3,4-benzotropolones. The 8-ethoxycarbonylated dimethyl-3,4-benzotropolone 50 obtained by this route was dimethylated to give goupiolone A (52). This synthesis encompasses 9 steps from 22, that is, half as many as the only previous synthesis (19 steps). A variant of our route afforded the 1,8-dibromide 54. Coupling with excess phenylboronic acid and ketal hydrolysis provided the diphenylated benzotropolone 56 and suggests a strategy, by which the natural bispulvinone aurantricholone (7) might be reached.
authors.affiliation: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104, Freiburg, Germany.|Current address: Carbogen-Amcis AG, Schachenallee 29, 5001, Aarau, Switzerland.
authors.forename: Deniz
authors.initials: D
authors.lastname: Arican
authors.affiliation: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104, Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Braukmüller
authors.affiliation: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstraße 21, 79104, Freiburg, Germany.
authors.forename: Reinhard
authors.identifier: http://orcid.org/0000-0002-9028-8436
authors.initials: R
authors.lastname: Brückner
mesh_terms: D044946:Biflavonoids / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D002392:Catechin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D054879:Halogenation; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D044946:Biflavonoids; C508389:benzotropolone; C000626318:goupiolone A; D010165:Palladium; D002392:Catechin
keywords: bromination reactions; dehydrobromination; natural products; nonbenzenoid aromatics; ring-closing olefin metathesis