The utilisation of cyclopropyl compounds in the synthesis of troponoids

Abstract

The fully regio-controlled synthesis of C1a-C12a mono-seco colchicine 133, as well as a number of structurally interesting analogues, has been achieved. The key feature employed in our approach to troponoid compounds of this type has been the incorporation of synthetic equivalents for α-tropolone anions 84 and 87 via dehydrobrominative ring expansion of C7-substituted7-bromobicyclo[4.1.0]heptan-2,3- and -3,4-diones respectively. The hydroxyl functionality present in tropolone 143 has been found to be a suitable progenitor for the C7-acetamido group in mono-seco colchicine 133. Studies directed towards the enantio-controlled introduction of the C7-acetamide moiety via asymmetric reduction of the prochiral ketone 152 are discussed. Various strategies to effect B-ring closure in mono-seco colchicine 133 and its congeners are presented. The novel preparation and dehydrogenative dimerisation of desacetamido mono-seco colchicine 174 is reported. An efficient synthesis of the naturally occurring tropone nezukone (16) has been accomplished via the novel rearrangement of bicyclic methylene cyclopropane 209. Evidence for the intermediacy of heptafulvenes in this conversion is described.