Supramolecular catalysis of a unimolecular transformation: Aza-cope rearrangement within a self-assembled host

TLDR: The utilization of a supramolecular metal–ligand assembly that is capable of catalyzing a unimolecular rearrangement is reported, and by inclusion into a sizeand shape-constrained reaction space these rearrangements are accelerated by up to three orders of magnitude compared to their background rates.

Abstract: Chemists have long envied the ability of enzymes to manipulate reaction energetics and specificity through steric confinement and precise functional-group interactions. The enormous rate accelerations that enzymes achieve at modest temperatures may be attributed to their high degree of complexity, and the synthetic chemist is hard pressed to create such well-constructed catalytic scaffolds. Yet in this regard, the utilization of supramolecular chemistry may have an advantage: supramolecular self-assembly facilitates the creation of large, complex structures from relatively simple precursors. Based on reversible weak interactions, such as hydrogen bonding or metal–ligand interactions, synthetic chemists have generated an array of self-assembled structures, diverse in architecture and composition. Some of these synthetic structures bear an internal cavity, and their interior can provide a new and very specific chemical environment, distinctly different from the exterior surroundings. The development of container-like molecules into chemically useful structures is an attractive goal, and their utilization as catalytic reaction chambers can parallel the enzyme function. The rate for a bimolecular Diels–Alder reaction, for example, was reported to be significantly accelerated in the presence of a supramolecular host, owing to the increase of effective concentrations of the two substrates when bound within the same capsule. Major challenges are a) to develop supramolecular systems capable of catalyzing unimolecular reactions, and b) to circumvent catalyst inhibition, a problem that frequently occurs when the cavity binds the reaction product more strongly than the substrate. We report herein the utilization of a supramolecular metal–ligand assembly that is capable of catalyzing a unimolecular rearrangement. Simply by inclusion into a sizeand shape-constrained reaction space these rearrangements are accelerated by up to three orders of magnitude compared to their background rates. Furthermore, the chemical properties of the reacting system provide an effective means of preventing product inhibition, which facilitates catalyst turnover. Raymond and co-workers have composed supramolecular tetrahedral structures of M4L6 stoichiometry through selfassembly of simple metal and ligand components. 11] In these assemblies the metal atoms are located at the vertices of the tetrahedron and six bis-bidentate catechol amide ligands span the edges (Figure 1). The tris-bidentate chelation of the metal centers renders them chiral (D or L), and the mechanical coupling through the rigid ligands results in the formation of exclusively homochiral assemblies (i.e. D,D,D,D or L,L,L,L). By virtue of the 12 overall charge, the assemblies are water soluble, yet they contain a flexible