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
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
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.