The 125th Anniversary of the Troger's Base Molecule: Synthesis and Applications of Troger's Base Analogues

In 2012 we celebrate the 125th anniversary of the unique molecule Troger's base (TB), first synthesized by Julius Troger in 1887. Being a V-shaped C2-symmetric chiral molecule, it possesses many interesting features. The TB field was reopened in 1985, when Craig S. Wilcox published the first crystallographic study of TB and described the synthesis and potential applications of TB analogues in supramolecular chemistry and in ligand design. This led to increasing interest in the development of synthetic methodology for TB analogues, initially for applications in the field of molecular recognition. In this review we give a short historical overview of TB and its chemical properties. In addition, we cover the fast progress in the development of synthetic methodologies to synthesize TB analogues that has taken place during recent decades. The functionalization of TB at almost any position in its skeleton is now possible and we discuss in detail recent developments in the functionalization of TB in the aromatic rings and in the methano bridge. The reopening of the functionalization of the diazocine ring itself is also discussed. In addition, progress in the synthesis of heterocyclic TB analogues and recent developments in the field of fused TB analogues are covered. The improvements in synthetic approaches have resulted in TB analogues with interesting properties that have inspired investigation of TB analogues in new fields of applications, among others as receptors, as molecular torsion balances, as ligands in asymmetric catalysis, as drug candidates, and as new materials for photo- and optical applications. The most recent developments in those fields are also discussed.