Active Template Strategies for the Assembly of Mechanically Interlocked Molecules

Abstract

Chemical templates have allowed the synthesis of increasingly complex mechanically interlocked molecular architectures. Transition metals are useful templating agents. Their coordination requirements result in the well-defined, threedimensional orientation of reactive fragments. Judicious choice of ligand and metal leads to a mechanically interlocked product upon covalent bond formation between the fragments. In such ‘passive’ templates a stoichiometric quantity of metal, with respect to the reacting components, is required. The metal atom acts as ‘glue’ until covalent, and consequent mechanical, bond formation has occurred. Recently in the Leigh group a fundamentally novel approach to interlocked architectures has been discovered and takes its cue from transition metal catalysis: in addition to inducing the necessary degree of preorganization in the system, the metal also mediates the covalent bond formation. This thesis describes further investigation of the original active template reaction—a ‘click’ reaction—and the subsequent extension of the strategy to new reactions and architectures. The effect of varying the macrocyclic ligand on the original Cu(I)-catalyzed 1,3- dipolar cycloaddition between alkynes and azides was investigated. Notably, the interlocked nature of the products provided new mechanistic insights into the nature of this widely used reaction. Following this, a Ni(II) active template was developed for the homocoupling of terminal alkynes. An unusual Ni/Cu system for this reaction was discovered and the resulting [2]rotaxanes were produced in excellent yield. The utility of the active template strategy was further demonstrated by the synthesis of a [3]rotaxane from a bifurcated macrocycle with a pyridyl bridging unit. Cu(I) catalyzed the formation of a triazole thread through each cavity, showing that multiple mechanical bonds can be formed from a single active template binding site. Lastly, the potential of carbene transfer reactions in the active template approach was investigated. A stoppered diazoester compound was synthesized and used in studies towards X-H insertion and cycloaddition reactions in the presence of a range of macrocyclic ligands