Bispidine Derivatives Synthesis and Interactions with Lewis Acids

University dissertation from Uppsala : Acta Universitatis Upsaliensis

Abstract: In this thesis, the improved synthesis and investigations into the properties of some 3,7-diazabicyclo[3.3.1]nonane (bispidine) derivatives are described. These compounds are structurally related to the naturally occurring lupanine alkaloids, they are of interest because of their cardiac antiarrhythmic function as well as their use as bases or ligands in organic chemical reactions. Their chemical properties are related to the presence of a rigid molecular scaffold with two nitrogen atoms that can be utilized for binding interactions with a variety of Lewis acids.An improved synthesis has been developed, providing access to bispidines via bispidinones while avoiding the use of highly toxic hydrazine, which is required as reducing agent in alternative methods.A series of bispidine derivatives with a variety of substituents were characterized regarding their basicity, which spans thirteen orders of magnitude. Correlations between structure and basicity are discussed and computational methods have been used to propose further derivatives with even higher basicity.The structures of several bispidine derivatives and their protonated forms have been characterized in the solid state by X-ray crystallography and in solution using NMR spectroscopy. Structure and solution dynamics in a sterically congested (?-allyl)palladium complex with a bispidine ligand have been investigated, revealing mechanistic insight into the dynamic process. Using a bulky bispidine as a temporary ligand for a (?3-propenyl) palladium complex, the novel adamantanoid [{(?3-propenyl)Pd}6(?3-OH)4] cluster was prepared.