The concept of self-assembling container molecules as yocto-litre reaction flasks is gaining prominence. However, the idea of using such containers as a means of protection is not well developed. Here, we illustrate this idea in the context of kinetic resolutions. Specifically, we report on the use of a water-soluble, deep-cavity cavitand to bring about kinetic resolutions within pairs of esters that otherwise cannot be resolved because they react at very similar rates. Resolution occurs because the presence of the cavitand leads to a competitive binding equilibrium in which the stronger binder primarily resides inside the host and the weaker binding ester primarily resides in the bulk hydrolytic medium. For the two families of ester examined, the observed kinetic resolutions were highest within the optimally fitting smaller esters.The simple act of compartmentalization is essential to chemistry. To an organic chemist, a round-bottomed flask is both a means of promoting a reaction by keeping reagents in, and stopping reactions by keeping species such as adventitious water out. In parallel with these concepts, in recent years supramolecular chemists have developed the idea of using container molecules as yocto-litre flasks to promote new reactions . However, there has been little progress in using container molecules as a means of protection. Indeed, to our knowledge, there has been only one reported example of supramolecular protection, where a primary amine product was prevented from over-alkylation by complexation to a cavitand 24 .While considering the idea of protection via compartmentalization, it occurred to us that one of the strengths of container molecules that fully envelop their guests is their ability to recognize subtle differences between the gross overall forms of molecules. Consequently, many of the container molecules in the literature could theoretically bring about not just the familiar kinetic resolution of stereoisomers [25][26][27][28] , but also the as yet unexplored topic of the kinetic resolution of constitutional isomers. Regarding the latter, there are of course many examples of compounds only being available as mixtures with constitutional isomers or constitutionally similar molecules. Hence, establishing a proof-of-principle that container molecules could effect such purifications could be quite powerful. In this Article, we report on the ability of supra-molecular nanocapsules to bring about the kinetic resolution of constitutionally isomeric long-chain esters. More specifically, we show that the capsule formed by water-soluble host * Correspondence and requests for materials should be addressed to B.C.G. bgibb@uno.edu. Author contributionsB.C.G. and S.L. conceived and designed the experiments. S.L. synthesized esters 2-6 and performed the experiments involving these guests. H.G. and A.T.H contributed equally to the syntheses and experiments involving esters 7-11. B.C.G. wrote the paper. Additional informationThe authors declare no competing financial interests. Supplementa...

No abstract