Hexameric capsule reactions

Aiming at demonstrating the potentialities of the hexameric capsule as a substrate selective nanoreactor, Scarso and coworkers extended the concept to a stoichiometric reaction. In particular, the steric hindrance due to the confined space within the cavity of the capsule was exploited in the substrate selective amide synthesis mediated by the cationic condensing agent 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride [47]. Similarly to the encapsulation of other cationic species, the cationic condensing agent that in... 

FIGURE 7.11 Hydration reaction of cyclohexyl isonitrile catalyzed by the hexameric capsule and inhibited by the presence of tetraethylammomum cation as a competitive guest for the cavity. (Adapted from Ref. [53].)... 

FIGURE 7.12 1,3-DipoIar cydoaddition reaction between diazoacetate esters and electron-poor alkenes like acrylate esters mediated by the hexameric capsule. (Adapted from Ref. [57].)... 

In particular, the reaction between cyclohexyl isonitrile and the TMSNj was investigated both in the presence and in the absence of the hexameric capsule in water-saturated chlorofotm-d. While the reaction did not occur spontaneously, in the presence of a catalytic amount of capsule (10 mol%), the reaction was complete in slightly more than 6 h (Fig. 7.14). Also in this case, rigid control experiments like the use of a weak Brpnsted acid of comparable acidity of the capsule and the use of resorcinol as a H-bond activating species similar to res-orcin[4]arene did not justily the catalytic activity observed. Experiments in the presence of the capsule occupied by a competitive tetraethylammonium guest showed a marked decrease of product formation after the same reaction time (33% yield), confirming the andal role of the encapsulation in the catalytic activity of the supramolecular capsule. 

La Sorella G, Sperni L, Stnikul G, Scarso A. Supramolecular Encapsulation of Neutral Diazoacetate Esters and Catalyzed 1,3-Dipolar Cycloaddition Reaction by a Self-Assembled Hexameric Capsule. ChemCatChem 2015 7 291-6. 

Shimizu S, Usui A, Sugai M, Suematsu Y, Shirakawa S, Ichikawa H. Hexameric capsule of a resorcinarene bearing fluorous feet as a self-assembled nanoreactor A Diels-Alder reaction in a fluorous biphasic system. Eur J Org Chem 2013 4734-7. 

By judicial characterization of the kinetics of the different intermediates and products in the reactions of different substrates and by comparing the results form alcohols and acetates, the mechanism for the formation of a series of terpenes from unsaturated alcohols in the presence of the hexamers of 6e was elucidated [54c]. For example. Fig. 31.12b shows the kinetics of one of the reactions performed in the presence of [6e6(H20)g]. This analysis showed that direct rotation of the transoid allylic cation to a cisoid cation, previously thought to be impossible, does occur [54c, d]. In this study it was shown that the hexameric capsule can encapsulate the terpene, stabilize the formed carbocations in a lipophilic environment (like in an enzyme pocket) which presumably increase their lifetimes (excluding water and... 

In another example of catalysis by the hydrogen-bonded hexamers, Shimizu et al. prepared Teflon-footed resorcin[4]arenes [56] (i.e., resorcin[4]arenes with per-fluorinated side chains) that form hexameric capsules in wet fluorous solvents. These capsules, several years later, were used to accelerate a Diels-Alder reaction in abiphasic system [56b]. 

An intriguing class of hexameric capsules are the hybrid systems based on metal organic pyrogallol[4]arene nano-capsules (MONCs) [57, 58], These systems were recently the subject of several reviews [57] but in recent years the field have witness a tremendous advancement, mostly by the group of Atwood. The first example of a MONC system was obtained by reacting C-proyl-3-ol-pyrogallol[4]arene obtained using the reaction shown in Fig. 31.13a with copper(II) nitrate [58a]. From the... 

Overall, the hexameric resorcin[4]arene capsule showed very interesting selective properties for the condensation reaction between carboxylic acids and amines mediated by a cationic carbodiimide-based condensing agent similarly to what was observed in the previous case for the alkyne hydration reaction, the capsule prefers the encapsulation of smaller and more compact substrates that react faster than longer ones. 

Another example of the use of a modified hexameric resorcin[4]arene capsule for the activation of a cycloaddition reaction was reported by Shimizu and... 

One of the most recent developments in the field is the use of the self-assembled hexameric resorcin[4]arene capsules as reaction vessels or nano-reactors where new chemistry and catalysis may occurs. There are only few such examples however in the past year or so several convincing and interesting examples were reported. The most interesting to date is the terpenes synthesis from unsaturated alcohols, which seems to mimic the action of cyclase enzymes. Clearly there is more chemistry to discover with these nano-vessels. 

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