Supramolecular stabilizing transition states

Supramolecular control of reactivity and catalysis is among the most important functions in supramolecular chemistry. Since catalysis arises from a differential binding between transition and reactant states, a supramolecular catalyst is, in essence, chemical machinery in which a fraction of the available binding energy arising from noncovalent interactions is utilized for specific stabilization of the transition state or, in other words, is transformed into catalysis. 

The rationale for the observed configuration (Scheme 3.29), is based on the X-ray structure of another a-carbamoyloxyorganolithium sparteine complex [185]. After deprotonation, the chelated supramolecular complex shown in the lower left is postulated. This structure contains an adamantane-like lithium-diamine chelate, and contains new stereocenters at the lithiated carbon and at lithium itself. Note that epimerization of the lithiated carbon would produce severe van der Waals repulsion between R and the lower piperidine ring, whereas epimerization at lithium produces a similarly unfavorable interaction between the same piperidine ring and the oxazolidine substituents. Thus, the carbamate is tailor-made for sparteine chelation of only one enantiomer of the a-carbamoyloxyorganolithium. These effects may provide thermodynamic stability to the illustrated isomer. To the extent these effects are felt in the transition state, they are also responsible for the stereoselectivity of the deprotonation. 

Reaction control throngh complexation of substrate by supramolecular host is a relatively new idea compared to the conventional approaches that involve simple coUisional attack or coordination of snbstrate to metal. Multiple non-covalent interactions in supramolecular assembly bind and locate a site-specific substrate in the right position, orientation and conformation near the catalyst or active site, stabilize the high-energy transition state, and eventually make the reaction faster and more selective. Typical examples are found in enzymatic reactions, which proceed with high specificity and efficiency in aqueous solutions under mild conditions. These observations in natural systems have inspired... 

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