Synthesis of nopinone from β-pinene-a journey revisiting methods for oxidative cleavage of C=C bonds in terpenoid chemistry

Abstract

The synthesis of nopinone from β-pinene is an interesting model reaction for the investigation of methods for the oxidative cleavage of C=C bonds. Nopinone is used as chiral component for the total synthesis of different ligands or natural compounds such as di- or sesquiterpenes, as well as for the production of pharmaceutically active components. The cleavage of the C(2)=C(10) bond in β-pinene by suitable oxidants leads to the replacement of the exo-methylene functionality by a carbonyl group, which is more suitable for subsequent synthetic steps and the construction of complex condensed ring systems. Oxidants such as ozone, potassium permanganate, or sodium periodate have been applied successfully for this reaction. Ozonolysis of the double bond follows the classical Criegee mechanism, after which the secondary intermediate is isolated and reductive workup yields the carbonyl products. Dihydroxylation of the double bond can be initiated by permanganate or periodate. Further oxidation leads to the same products known from ozonolysis. Periodate oxidations in particular can be supported by catalysts such as RuCl3 or OsO4, because the oxidant is generally too weak to dihydroxylate the double bond. OsO4-catalyzed reactions, for example, can take advantage of a co-oxidant such as trimethylammonium N-oxide for the dihydroxylation step. Other oxidants such as hydrogen peroxide or dioxygen have also been tested but with minor success with respect to conversion or selectivity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.