No abstract

Nanoscale molecular flasks have increasingly been used to promote novel reactivity or impart powerful selectivity through precise, noncovalent interactions with substrate molecules.Encapsulation of substrate molecules within these host structures may stabilize reactive species 1 or, conversely, promote substrate reactivity. 2 The confined environment within these supramolecular hosts has also been demonstrated to impart remarkable size and shape selectivity. Employing these supramolecular assemblies in asymmetric catalysis remains an important challenge.4 Chiral building blocks may be used to construct chiral supramolecular assemblies, in some cases generating additional elements of chirality during the assembly of these structures. While chiral supramolecular assemblies have been shown to carry out enantioselective stoichiometric reactions, or catalyze reactions with modest ee, a highly enantioselective catalytic transformation has not yet been demonstrated. 5 We now report such catalysis. 12-assembly 1, a self-assembling supramolecular structure. 6 In collaboration with the Bergman group, this cluster has been shown capable of catalyzing a variety of chemical transformations with low catalyst loadings and enzyme-like kinetics, including the aza-Cope rearrangement and the hydrolysis of orthoformates and acetals.7 Importantly, 1 is chiral due to the three bidentate catecholates coordinating each gallium center (Figure 1). Mechanical coupling between the four vertices enforces the same helical configuration ( or ) at each metal center.8 As a result, two enantiomeric forms of 1 exist,  and . Though 1 is synthesized as the racemate, addition of (-)-N'-methylnicotinium iodide (S-nicI) causes the spontaneous resolution of the two enantiomers, allowing access to pure -(S-nic  1, where  denotes encapsulation) and pure -(S-nic  1). Ion exchange chromatography allows isolation of each enantiomer as the tetramethylammonium salt. 9For this study, the aza-Cope rearrangement of enammonium substrates was selected (Figure 2) to evaluate 1 as an enantioselective catalyst.9c Encapsulation of enammonium substrates within 1 enforces a reactive conformation. The product iminium ions are vulnerable to hydrolysis, producing neutral aldehydes which are not encapsulated in 1. As long as R 1 ≠ R 2 , the rearrangement generates a chiral center and potentially enantioselective within chiral assembly 1. Since obtaining suitable quantities of enantiopure K 12 1 is not practical, reactivity compatible with (NMe 4 ) 12 1 is required. . Enammonium substrates 2 are more tightly bound than NMe 4 + , enabling efficient catalysis within (NMe 4 ) 12 1. We describe here the application of enantiopure 1 in catalyzing the aza-Cope rearrangement, achieving enantioselectivities for host-guest catalysis that are remarkable in view of the fact that the cavity bears no reactive functional groups.

Gold(I)-phosphine complexes are readily encapsulated by a tetrahedral supramolecular host (Ga(4)L(6)). We have investigated the catalytic activity of the resulting complexes for the intramolecular hydroalkoxylation of allenes. The catalytic activity of Me(3)PAuBr was increased 8-fold by encapsulation, as determined by initial rate kinetics, and we observed up to 67 catalytic turnovers by Me(3)PAu(+) encapsulated in Ga(4)L(6).