Since the trailblazing discoveries of Lehn, Cram and Pedersen, supramolecular chemistry has established itself as a cornerstone of organic chemistry. Supramolecular hosts offer defined microenvironments that mimic the active sites of enzymes, utilizing specific host-guest interactions to enable remarkable rate enhancements and product selectivity. The development of a diverse array of self-assembled hosts, coupled with the increased demand for shorter and greener synthetic routes, have spurred significant progress in the field of supramolecular catalysis. This review covers recent advances in the field, ranging from novel organic reactivity aided by supramolecular hosts to catalytic cooperation between hosts and organometallic compounds or metal nanoparticles. Strides have also been made in the synthetic application of these hosts in siteselective substrate modifications and challenging photochemical reactions. These efforts have enabled the incorporation of non-covalent macromolecular catalysis in natural product syntheses, evidencing their unique advantages as a synthetic tool, and their powerful potential for practical applications.
ABSTRACT:We have demonstrated that the microenvironment of a highly anionic supramolecular catalyst can mimic the active sites of enzymes and impart rate accelerations of a million-fold or more. However, these microenvironments can be challenging to study, especially in the context of understanding which specific features of the catalyst are responsible for its high performance. We report here the development of an experimental mechanistic probe consisting of two isostructural catalysts. When examined in parallel transformations, the behavior of these catalysts provides insight relevant to the importance of anionic host charge on reactivity. These two catalysts exhibit similar host-substrate interactions, but feature a significant difference in overall anionic charge (12 − and 8 − ). Within these systems, we compare the effect of constrictive binding in a net neutral aza-Cope rearrangement. We then demonstrate how the magnitude of anionic host charge has an exceptional influence on the reaction rates for a Nazarov cyclization, evidenced by an impressive 680-fold change in reaction rate as a consequence of a 33% reduction in catalyst charge. ■ INTRODUCTIONStarting from humble beginnings, 1−4 some supramolecular catalysts now rival enzymes in accelerating rates of catalyzed reactions. 5−18 In contrast to typical homogeneous small molecular catalysts, self-assembled supramolecular catalysts achieve these rate accelerations by emulating the mechanisms of enzymes. Like enzymatic active sites, the microenvironments within these assemblies encapsulate substrate molecules with specificity and utilize noncovalent host−guest interactions to induce significant rate accelerations and impart remarkable selectivities.19−22 Thus, supramolecular hosts are important to study not only for the design of improved synthetic catalysts but also to advance our understanding of the governing principles that underlie enzymatic catalysis.The catalytic activity of supramolecular hosts is dictated by multiple parameters, including overall charge, cavity size, and the degree of solvent exclusion. 23,24 However, it is often challenging to deconvolute the consequences of these specific features of supramolecular catalysts on reactivity, and such studies are lacking. We report here a powerful experimental approach that exploits the modularity of a reported metal− ligand supramolecular assembly, enabling the isolation of host charge to investigate its influences on reaction rates. Supramolecular host Ga-1 (K 12 Ga 4 2 6 ) developed by Raymond and co-workers was chosen as a suitable candidate for the development of a catalyst with varied charge. The unusually large anionic host charge (12 − ) is due to four trianionic homochiral Ga(III) triscatecholate vertices, which enforce overall T symmetry upon the framework (Figure 1 we envisioned an experimental investigation of the specific role of charge in these reactions by changing the metal vertices in Ga-1 to reduce the overall host charge while maintaining the chemical structure and geometry of th...
Supramolecular hosts offer defined micro-environments that facilitate selective host-guest interactions, enabling reactivity that would otherwise be challenging in bulk solution. While impressive rate enhancements and selectivities have been reported, similar reactivity can often be accessed through modifications of reaction conditions even in the absence of the host. We report here an oxidative addition of aryl halides across the metal centers in Cu(I) and Pd(II) organometallics that is assisted by the presence of a supramolecular host, realized via electrostatic stabilization and increased local substrate concentrations. When reaction conditions were screened to assess background reactivity, alternative reactivity (typically decomposition) resulted, indicating that encapsulation led to host-selective reaction trajectories.
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