Molecule (Reaction) of the Month

Pericyclic Reactions in Cavities

A pericyclic reaction is one in which bonds are made or broken in a concerted cyclic transition state. The accepted wisdom for such reactions is that they have several characteristic properties, once of which is that no catalyst is needed to promote the reactions. In the last twenty years however, many examples of catalysed pericyclic reactions have been discovered, included those mediated by transition metals, and by metals acting as Lewis acids. It has also been known for some time that it is also possible to accelerate some pericyclic reactions by the use of pressure, especially for those reactions involving a substantial decrease in volume such as Diels-Alder cycloadditions. This has prompted much recent interest in replacing simple pressure for inducing the reaction, by persuading the reactants to enter a cavity or binding site instead. Examples are now known for using the crystal lattice of a simple hydrogen bonded organic molecule to achieve this, as well as an "abzyme" or enzyme produced from artificial catalytic antibodies.

A Cavity formed in the crystal lattice of an organic molecule

The resorcinol based aromatic molecule shown below forms hydrogen-bonded lattices in the solid state, the cavities of which are large enough to accomodate three small organic molecules, such as methyl methacrylate and cyclohexadiene. Click here to see a 3D model of the cavity and the reagents trapped inside. Other types of cavities formed from covalently bound porphyrinic-hosts (as opposed to cavities formed via intermolecular hydrogen bonds) have been synthesised by Jeremy Sanders at Cambridge. Calculated models for these can be seen here.

For further information, see K. Endo, T. Koike, T. Sawaki, O. Hayashida, H. Masuda and Y. Aoyama, J. Am. Chem. Soc., 1997, 119, 4117.

Pericyclic Reactions in Enzymes.

Pericyclic reactions are unusual in that very few enzymes which catalyse such reactions are known. Artificial catalytic antibodies ('abzymes') can be created which can perform this feat, and a prominent recent example is the isolation and structural determination of the so-called "Diels-Alderase". Here, the Diels-Alder transition state was mimicked using an derivative of a bicyclo-octane know as FRA. This acts as an inhibitor to the real Diels-Alder reactions, and the enzyme can be crystallised out with FRA trapped in the active site.

Another catalysed pericyclic reaction is the [3,3] sigmatropic type Claisen rearrangement of Chorismate to pre-phenate, a reaction induced by the enzyme Chorismate mutase for the Claisen rearrangement.

For further information on Diels-Alderase, see Katayama_K, Kobayashi_T, Oikawa_H, Honma_M, Ichihara_A, Biochimica Et Biophysica Acta-Protein Structure And Molecular Enzymology, 1998, Vol.1384, pp.387-395; Heine_A, Stura_EA, YliKauhaluoma_JT, Gao_CS, Deng_QL, Beno_BR, Houk_KN, Janda_KD, Wilson_IA, SCIENCE, 1998, 279, No.5358, pp.1934-1940.

Copyright H. S. Rzepa, 1999. These examples are all culled from the notes on Pericyclic reactions, a lecture course given at Imperial College to second year students.