Microwave-Based Reaction Screening: Tandem Retro-Diels–Alder/Diels–Alder Cycloadditions of o-Quinol Dimers

We have accomplished a parallel screen of cycloaddition partners for o-quinols utilizing a plate-based microwave system. Microwave irradiation improves the efficiency of retro-Diels–Alder/Diels–Alder cascades of o-quinol dimers which generally proceed in a diastereoselective fashion. Computational studies indicate that asynchronous transition states are favored in Diels–Alder cycloadditions of o-quinols. Subsequent biological evaluation of a collection of cycloadducts has identified an inhibitor of activator protein-1 (AP-1), an oncogenic transcription factor.