Thermal and (thermo-reversible) photochemical cycloisomerization of 1H-2-benzo[c]oxocins; From synthetic applications to the development of a new molecular photothermal switch

A novel photothermal molecular switch based on the reversible cyclization of 1H-2-benzo[c]oxocins to dihydro-4H-cyclobuta[c]isochromenes has been developed. The switching mechanism involves a light-triggered ring-contraction of 8 membered 1H-2-benzo[c]oxocins to 4,6-fused O heterocyclic dihydro-4H-cyclobuta[c]isochromene ring systems, with reversion back to the 1H-2-benzo[c]oxocin state accessible through heating. Both processes are unidirectional and proceed with good efficiency, with switching properties—including reversibility and half-life time—easily adjusted via structural functionalization. Our new molecular switching platform exhibits independence from solvent polarity, originating from it’s neutral-charge switching mechanism, a property highly sought after for biological applications. The photoinduced ring-contraction involves a [2+2] conjugated-diene cyclization that obeys the Woodward–Hoffmann rules. In contrast, the reverse process initiates via a thermal ring-opening (T > 60oC) to produce the anti-Woodward–Hoffmann product, proposed to proceed via an ortho-quinodimethane (o-QDM) intermediate. The proposed switching mechanisms are supported by experimental observations and density functional theory (DFT) calculations. Other transformations of 1H-2-benzo[c]oxocins were found upon altering reaction conditions: prolonged heating the 1H-2-benzo[c]oxocins at significantly elevated temperature (72 h at 120°C), with the resulting dihydronaphthalenes formed via the o QDM intermediate. These reactions also proceed with good chemoselectivities, providing new synthetic protocols for motifs found in several bioactive molecules, but are otherwise difficult to access.