A novel approach for functionalising and separating Tröger's Base Analogues

Abstract: Tröger’s Base (TB) is a bicyclic compound containing a methanodiazocine group between two aromatic rings. The methylene bridge forces the molecule to have a bent formation; thus, the aromatic rings are close to 90 degrees relative to each other, resulting in a rigid concave aromatic cavity. These unique properties make TB a great candidate as a molecular cleft compound and a good structure as a molecular receptor towards unfunctionalised molecules. The Tröger’s Base framework has therefore been found to be a useful building block in supramolecular chemistry. The Tröger’s Base project aims to complete a total synthesis of a linearly fused heptakis Tröger’s Base analogue. As a part of this project, the goals of this master thesis are to acylate the benzylic position of a TB analogue and to separate the resulting diastereomers with dry column vacuum chromatography. In order to achieve these two goals, six synthesis steps have been performed, starting from a commercially available aniline analogue. The aniline analogue was halogenated, followed by a condensation reaction to form the first TB analogue. After four more synthesis steps, including dehalogenation, Pd-catalyzed amination, amine protection, and acylation, where the benzylic position of a TB analogue finally functionalised. Afterwards, one of the diastereomers was successfully separated from the mix of diastereomers with a dry vacuum column using silica. As a result, this thesis work has shown it possible to acylate a TB analogue at the benzylic position and shown that the resulting mix of diastereomers is separable by dry column vacuum chromatography. In addition, the work has given valuable TB analogues, which can be used in further synthesis in the Tröger’s Base project.