Unusual radical reaction powered by strained substrates

A mild and simple method to access pharmaceutically important bicyclic compounds, the bicyclohexane motif, has been developed using only the innate reactivity of two strained substrates. The new reaction proceeds via an unusual formal σ bond insertion, exploiting the diradical-like character of the starting materials to drive the reaction without activation.

Aromatic rings are common in drug compounds, largely owing to their ease of synthesis and manipulation. However, undesirable properties arising from these flat, unsaturated structures mean that increasingly the pharmaceutical industry is seeking to replace these motifs with rigid 3D frameworks. Bicyclohexanes (BCHs) are an important structural mimic of di-substituted aromatics and this scaffold has already been incorporated into several promising drug candidates.