Boosting Molecular Complexity with O 2 : Iron-Catalysed Oxygenation of 1-Arylisochromans through Dehydrogenation, Csp 3 -O Bond Cleavage and Hydrogenolysis.

Oxidative cleavage of the Csp(3)-O bond in 1-arylisochromans with stoichiometric oxidants, such as CrO3/H2SO4, has been practiced for decades in synthetic chemistry. Herein, we report that a structurally well-defined Fe-II-pyridyl(bis-imidazolidine) catalyst promotes the aerobic oxygenation of 1-arylisochromans, affording highly selectively 2-(hydroxyethyl)benzophenones, compounds of potential for neuroprotective agents. Key intermediates have been isolated, indicating that the reaction proceeds through dehydrogenative oxygenation of the isochromans at the 1-position, Csp(3)-O bond cleavage at the iron centre and hydrogenolysis of the resulting Fe-O bond with the H-2 generated from the dehydrogenation step. In the absence of H-2 but under iron catalysis, the peroxide intermediate is converted into an unexpected ketal compound, which transfers into a 2-(hydroxyethyl)benzophenone when both O-2 and H-2 are admitted. The unique ability of the iron catalyst for oxygenation and hydrogenation in the same catalytic process under mild conditions allows for the stepwise preparation of a variety of isolable oxygenated products on a preparative scale, circumventing the need for using wasteful and/or toxic oxidants.