(+)-iso-Phomopsene (and friends)

Long-time readers of this column will know that I love a cycloaddition – I’ve probably run hundreds of them over my career as an organic chemist. There was even a two-hour period immediately before my PhD viva where I could credibly claim to understand the fiendishly complex Woodward–Hoffman rules that were used to rationalise their outcomes in the pencil-and-paper days before computational chemistry. However, I have far less experience with their rarer cousin, the electrocyclisation.

On the surface, these reactions are pretty simple: electrons dance around a cyclic transition state, resulting in a double bond lost and a single bond gained. Although not obvious at a glance, the stereochemical outcome is actually highly predictable, providing your grasp of molecular orbital theory is strong and you have a spare 15 minutes. But if you ask me, predicting the product is the easy part. The greater challenge from a total synthesis point of view is spotting where these reactions fit into a route and can actually add value. Most people, myself included, tend to retrosynthesise by breaking bonds, not moving them. And after the effort of setting up an elaborate substrate to rearrange with often a minimal jump in complexity, you’re left with the feeling that the juice wasn’t worth the squeeze.