Enantioselective Phenolic α-Oxidation Using H2O2 via an Unusual Double Dearomatization Mechanism.

Feedstock aromatic compounds are compelling low-cost starting points from which molecular complexity can be generated rapidly via oxidative dearomatization. Oxidative dearomatizations commonly rely heavily on hypervalent iodine or heavy metals to provide the requisite thermodynamic driving force for overcoming aromatic stabilization energy. This article describes oxidative dearomatizations of 2-(hydroxymethyl)phenols via their derived bis(dichloroacetates) using hydrogen peroxide as a mild oxidant that intercepts a transient quinone methide. A stereochemical study revealed that the reaction proceeds by a new mechanism relative to other phenol dearomatizations and is complementary to extant methods that rely on hypervalent iodine. Using a new chiral phase-transfer catalyst, the first asymmetric syntheses of 1-oxaspiro[2.5]octa-5,7-dien-4-ones were reported. The synthetic utility of the derived 1-oxaspiro[2.5]octadienones products is demonstrated in a downstream complexity-generating transformation.

Dearomatization of Cyclic Diphenylhydrazines: Harnessing the o-Semidine Rearrangement for the Synthesis of Spirocyclic Tetrahydroquinolines.

The synthesis of novel tetrahydroquinoline-containing spirocycles has been achieved through an acid-promoted dearomatization of cyclic diarylhydrazines. The reaction, proceeding through a dearomative o-semidine rearrangement, furnishes a stable, yet reactive spirocyclohexadieniminium ion, which can further be used as an electrophile or a diene in a one-pot sequence. These transformations efficiently produce novel diazaspirocycles and allow for further synthetic elaboration of the cyclohexadienamine products.

Phenolic Oxidation Using H2O2 via in Situ Generated para-Quinone Methides for the Preparation of para-Spiroepoxydienones.

Phenols are attractive starting materials for the preparation of highly substituted cyclohexane rings via dearomative processes. Herein we report an efficient preparation of dearomatized 1-oxaspiro[2.5]octa-4,7-dien-6-ones (para-spiroepoxydienones) via the nucleophilic epoxidation of in situ generated para-quinone methides from 4-(hydroxymethyl)phenols using aqueous H2O2. The developed protocol bypasses the need for stoichiometric bismuth reagents or diazomethane, which are frequently deployed for p-spiroepoxydienone preparation. The p-spiroepoxydienones are further elaborated in numerous downstream complexity-building transformations.