The first really interesting reaction seen by Organic Chemistry students is the Diels-Alder [4+2] cycloaddition, an example of a concerted process where all the bond making and breaking take place concomitantly. The S_N2 is also a concerted process, however the Diels-Alder reaction is a gem because of the high density of relative stereochemistry that can be established in a single synthetic step. The most interesting and unique of all organic reactions learned fall within the narrow category of sigmatropic rearrangements, intramolecular pericyclic processes wherein one σ-bond is exchanged for another σ-bond. Example reactions are the Cope and Claisen rearrangements.

The Cope rearrangement, published by Arthur C. Cope in 1940, is a [3,3] sigmatropic rearrangement of 1,5-dienes.¹ When 3-phenyl-1,5-hexadiene is heated at 178°C, trans-1-phenyl-1,5-hexadiene is isolated in a 72% yield.

It should be no surprise by now that any explanation of the stereochemical outcome of a reaction proceeding via a 6-membered transition state is best effected via conformational analysis. The trans-isomer is thermodynamically favored because it places the phenyl group in an equatorial position during the transition state, whereas the cis-isomer would have it in an axial position.

When oxygen is incorporated into the reactive species as an allyl vinyl ether, the sigmatropic rearrangement is known as the Claisen rearrangement. Heating 2-propenyloxybenzene at 200°C affords 2-(2-propenyl)phenol is in a 75% yield.

The ketone intermediate of the reaction is driven by aromaticity to tautomerize completely to the phenol form.

One last example in this class of reactions is the oxy-Cope rearrangement, not to be confused with the Claisen rearrangement.

A more functional example of this reaction is seen in the rearrangement of a bicyclooctane in favor of a cis-decalin ring system.

When the reaction is effected on the free 3° alcohol via thermolysis, a 50% yield of the product is obtained. Professor David Evans et al.² showed that the reaction can be accelerated between 10¹⁰ to 10¹⁷ and the yield improved to >90% when proceeding via the oxo-anion using a K⁺/18-crown-6 system in tetrahydrofuran. When it is the desired transformation, the oxy-Cope can be highly favorable; when it is a potential side-reaction, the alcohol functionality requires a protective group.

1. Cope, A.C. J. Am. Chem. Soc. 1940, 62, 441.
2. Evans, D.A.; Golob, J. Am. Chem. Soc. 1975, 97, 4765.

© 2011 Joseph Lennox, Ph.D.

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