Exploring diradical chemistry: a carbon-centered radical may act as either an anion or electrophile through an orbital isomer.

Diradical intermediates, formed by thermolysis of alkynylcyclobutenones, can display radical, anion, or electrophilic character because of the existence of an orbital isomer with zwitterionic and cyclohexatrienone character. Our realization that water, alcohols, and certain substituents can induce the switch provides new opportunities in synthesis. For example, it can be used to shut down radical pathways and to give access to aryl carbonates and tetrasubstituted quinones.

New insights into cyclobutenone rearrangements: a total synthesis of the natural ROS-generating anti-cancer agent cribrostatin 6.

Aryl- and heteroarylcyclobutenone rearrangements proceed in excellent yield under continuous-flow conditions. The former shows a Hammett correlation with σ(I) providing strong evidence that electrocyclisation is the rate-determining step and has a late transition state. The reaction has been modelled by using DFT and CCSD(T) methods, with the latter giving excellent correlation with the experimental rate constant. A short and efficient total synthesis of cribrostatin 6, an anti-neoplastic and anti-microbial agent, provides a topical demonstration of the value of this method.