SummaryThe 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.
Nachhaltige Oxidationen von Aryl(di)azinylmethanen zu Aryl(di)azinylketonen gelingen mit Kupfer‐ und Eisenkatalysatoren sowie O2 als Oxidationsmittel. Die Nützlichkeit der Methode wird durch die Synthese von 6‐(4‐Methylbenzoyl)pyridin‐2‐carbaldehyd, einer Zwischenstufe bei der Herstellung des Wirkstoffs Acrivastin, illustriert.
The reaction of 6-chloro-1-methylpyrazin-2(1H)-one with Grignard reactants followed by quenchingwith different electrophiles gave access to a variety of 3,6-difunctionalized 1methylpyrazin-2(1H)-ones. This regioselective three-component reaction represents the first example of a tele-nucleophilic substitution of hydrogen (SN H ) in which the anionic σ H adduct is quenched by electrophiles (other than a proton) before elimination takes place. Quenching the reaction with iodine (I2) or bromine (Br2) provides an alternative reaction pathway, yielding a 3-functionalized 6-chloro-1-methylpyrazin-2(1H)-one or 5-bromo-6-chloro-1-methylpyrazin-2(1H)-one, respectively. The halogens present offer opportunities for further selective transformations.
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