Synthesis of (Nor)-Adamantane Derivatives via [1,2]-Alkyl Migration Reactions

Abstract

In this thesis, selected results on the rearrangement between the noradamantane and the adamantane hydrocarbon cage are presented, as well as their application in organic synthesis. This reversible reaction proceeds through a Wagner-Meerwein rearrangement – a [1,2]-alkyl shift of a carbocation – either leading to the diamondoid structure of adamantane or the contracted derivative, depending on the structural elements surrounding the carbocation and the reaction conditions. The rearrangement was used to synthesize 1,2-functionalized heterocyclic adamantylamines from noradamantane iminium triflates. In the classical Wagner-Meerwein reaction, the alkyl shift forms a tertiary from a secondary carbocation, following the way to the energetically more stable structure. When iminium salts are rearranged, the stability is inverted since the secondary carbocation is stabilized by its iminium ion resonance structure. High temperatures and a trapping nucleophile (i.e., a Friedel-Crafts acceptor) are needed to push the equilibrium to the targeted adamantyl cage. Deeper investigations provided insight into the mechanism of the reaction, its difficulties, and its limits. Postfunctionalization of one of the target molecules showed the possibilities for further transformation of the compounds, demonstrating their potential use in medicinal research and synthetic or material chemistry. In an additional publication, the procedure was reversed. Contrary to the previous protocol, the rearrangement starts at the adamantane structure and proceeds in the direction of the iminium salt. The reaction yielded the targeted noradamantane and ring-contracted diamantane derivatives – after hydrolysis of the iminium salt – with an adjacent carbaldehyde function. These compounds can be used as precursors for the above-mentioned iminium triflate rearrangements and thus increase the number of possible 1,2-functionalised adamantanes accessible through this route.