Size- and Shape-Selective Catalysis with a Functionalized Self-Assembled Cage Host

Abstract

A self-assembled Fe4L6 cage with internally oriented carboxylic acid functions was shown to catalyze a variety of dissociative nucleophilic substitution reactions that proceed via oxocarbenium ion or carbocation intermediates. The catalytic behavior of the cage was compared to that of other small acid catalysts, which illustrated large differences in reactivity of the cage-catalyzed reactions, dependent on the structure of the substrate. For example, only a 5% cage confers a 1000-fold rate acceleration of the thioetherification of vinyldiphenylmethanol when compared to the rate with free carboxylic acid surrogates but only a 52-fold acceleration in the formation of small thioacetals. Multiple factors control the variable reactivity in the host, including substrate inhibition, binding affinity, and accessibility of reactive groups once bound. Simple effective concentration increases or the overall charge of the cage does not explain the variations in reactivity shown by highly similar reactants in the host: small differences in structure can have large effects on reactivity. Reaction of large spherical guests is highly dependent on substitution, whereas flat guests are almost unaffected by size and shape differences. The cage is a promiscuous catalyst but has strong selectivity for particular substrate shapes, reminiscent of enzymatic activity.

Modifying the internal substituents of self-assembled cages controls their molecular recognition and optical properties

“…In addition, as the binding is quite remote from the ligand protons, only small shifts in the 1 H NMR are seen. 9 In contrast, large changes in UV absorbance can be seen upon titration of neutral guests into 1.0 μM solutions of cage in CH 3 CN (Fig. 7, ESI Fig.…”

“…We have previously described the synthesis, molecular recognition and catalytic properties of a series of Fe II 4 L 6 cages with internalized functional groups, based on a 2,7-diarylfluorene scaffold. 9 The slightly bent, V-shaped ligands allow internalization of groups such as carboxylic acids 9 a–c or dimethylamino groups, 9 d while retaining the ability to form M 4 L 6 tetrahedra with a cavity that is capable of binding and activating multiple different species on the interior. The 2,7-diarylfluorene scaffold displays 12 of these groups on the cage interior (two from each ligand), and while assembly is still possible with this level of internal packing, it does limit the types of functional groups that can be positioned on the cage interior.…”

Reactions in Endohedral Functionalized Cages

“…In addition to the reactions depicted in figure 6, cage 12 has been shown to catalyze the thioether/ether exchange in acetals and the thioetherification of tertiary allylic alcohols. [43] Derivatives of building block 13 have been synthesized as well. An example is the diamine functionalized building block 16 that assembles in the presence of 2-formylpyridine (14) and Fe(ClO 4 ) 2 to cage 17 (Figure 7).…”

“…Interestingly, the size of the acetals that can be converted is limited, as bulky once such as 9‐(dimethoxymethyl)anthracene give way lower yields. In addition to the reactions depicted in figure 6, cage 12 has been shown to catalyze the thioether/ether exchange in acetals and the thioetherification of tertiary allylic alcohols [43] …”

Moderated Basicity of Endohedral Amine Groups in an Octa‐Cationic Self‐Assembled Cage

“…The exact number of ClO 4 − anions is unclear—Figure 2d shows a minimized structure of cage 1 with twelve HClO 4 in the cavity, showing that multiple ClO 4 − ions can certainly fit in the interior. The host:guest properties of the cage suggest that the cavity of 1 is blocked, presumably by ClO 4 − ions: when a neutral guest (diethyl 2,2′‐(2,7‐dibromofluorene)‐diacetate, [13a] see Figures S52–S55) was added to the cage, no binding was seen, whereas it shows strong affinity for acid cage 3 ( K a ( 3 )=6.9±1.2×10 3 M −1 ) [13c] …”