Boosting Molecular Complexity with O₂: Iron‐Catalysed Oxygenation of 1‐Arylisochromans through Dehydrogenation, Csp³−O Bond Cleavage and Hydrogenolysis

Abstract

Oxidative cleavage of the Csp3−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 FeII–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, Csp3−O bond cleavage at the iron centre and hydrogenolysis of the resulting Fe−O bond with the H2 generated from the dehydrogenation step. In the absence of H2 but under iron catalysis, the peroxide intermediate is converted into an unexpected ketal compound, which transfers into a 2‐(hydroxyethyl)benzophenone when both O2 and H2 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.

Catalytic Asymmetric Synthesis of Chiral Bis(indolyl)methanes Using a Ts-PyBidine–Nickel Complex

“…Although the original PyBidine ( L2 ) was developed using N -benzyl diphenyldiamine (i.e., Bn-PyBidine), the substituent on the nitrogen atom can be changed. Among the N -substituents examined, a tosylated PyBidine (Ts-PyBidine) , was effective in improving the enantioselectivity of 3aa at up to 70% ee. Surprisingly, the other cationic first-row transition metal complexes possessed significantly greater catalytic activity (entries 7–9).…”

Dehydrogenative α‐Oxygenation of Cyclic Ethers by a High‐Valent Manganese(IV)‐Oxo Species

“…Experimentally we found that the [(trans‐BPP)Mn II (OTf) 2 ] complex catalyzes efficient oxidation of 1‐arylisochromanes, affording 2‐(hydroxyethyl)benzophenones in high yields (Scheme 2). We have previously reported an iron complex that is capable of activating O 2 and catalyzes similar reactions with O 2 as the oxidant, albeit requiring a higher temperature and longer reaction time [9c] . In contrast, the structurally similar [(cis‐BPP)Mn II (OTf) 2 ] is much less active, affording a yield of <10 % in the case of 1‐phenylisochromane.…”