title: Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen.
abstract: The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP-MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit.
authors.affiliation: Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Sterckx
authors.affiliation: Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: De Houwer
authors.affiliation: Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Carl
authors.initials: C
authors.lastname: Mensch
authors.affiliation: Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Herrebout
authors.affiliation: Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Kourosch Abbaspour
authors.initials: KA
authors.lastname: Tehrani
authors.affiliation: Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
keywords: base metal; benzylic; catalyzed; molecular oxygen; oxygenation