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An efficient regioselective method for oxidation of phenols to o-quinones is reported. When this procedure is combined with a subsequent reduction, it proves to be useful for the construction of a variety of catechols.o-Quinones undergo a variety of reactions. For example, these species can be reduced to the corresponding catechol. 1,2 In addition, as a highly reactive 8π-electron system, o-quinones display two 4π components as potential sites for Diels-Alder reactions. 3 The selectivity between sites results from the polarizability of the complementary 2π component. For example, polarized alkenes such as enamines add to the external dione to restore aromaticity and yield a dioxin, 4 while less polarized alkenes such as styrene add to the cyclohexadiene portion to yield a [2.2.2]bicyclooctane. 5 Because o-quinones display four 2π components, there are varieties of [3 + 2] cycloaddition formats as well. The dipolar addition can be controlled so that either a carbonyl or an olefin moiety undergoes reaction. 6 In addition, there are many other reactions where the functional groups of o-quinones can be distinguished. For example, cesium fluorosulfate converts the most electrophilic carbonyl group of an o-quinone to 2,2-difluorocyclohexadienone, 7 while addition of a Wittig reagent can generate a benzopyran-2-one. 8 The ring olefins can be distinguished in nonsymmetric o-quinones: the most nucleophilic olefin is either oxidized or cleaved with peroxyacid 9 and Pb 10 reagents, respectively.Such versatility clearly suggests that unsymmetric o-quinones should be of considerable synthetic use. However, a convenient means to access a range of differently substituted oquinones has been lacking due in part to the difficulty in accessing the appropriately substituted catechol. A thorough survey of the literature reveals a few methods that allow for the regioselective conversion of a phenol to an o-catechol. 11 To the best of our knowledge, there are no previous examples of a regioselective procedure for the direct conversion of a phenol into an o-quinone. Oxidants such as Fremy's radical, 12 MeReO 3 -H 2 O 2 ,13 dimethyldioxirane, 14 and benzeneseleninic anhydride 15 are indiscriminate or favor oxidation of the para position unless blocked with a substituent.* To whom correspondence should be addressed.. † Undergraduate research participant supported by the California Alliance for Minority Participation (CAMP) in science. Supporting Information Available:A general experimental procedure along with the crude 1 H NMR spectra used to estimate yields for o-quinones 4, 6, 8, 11, 13, 15, 17, 19, and 23 and full spectral characterization of 5, 20, 21, and 24. This material is available free of charge via the Internet at http://pubs.acs.org. (Figure 1). NIH Public AccessBecause of this unexpected yet pleasing transformation, we paused to investigate the potential of this novel transformation. Table 1 illuminates the scope of this procedure. The oxidation of an array of phenols (0.1 M in a respective solvent) with a suspensi...

ConspectusAn ortho-quinone methide (o-QM) is a highly reactive chemical motif harnessed by nature for a variety of purposes. Given its extraordinary reactivity and biological importance, it is surprising how few applications within organic synthesis exist. We speculate that their widespread use has been slowed by the complications that surround the preparation of their precursors, the harsh generation methods, and the omission of this stratagem from computer databases due to its ephemeral nature.About a decade ago, we discovered a mild anionic triggering procedure to generate transitory o-QMs at low temperature from readily available salicylaldehydes, particularly OBoc derivatives. This novel reaction cascade included both the o-QM formation and the subsequent consumption reaction. The overall transformation was initiated by the addition of the organometallic reagent, usually a Grignard reagent, which resulted in the formation of a benzyloxy alkoxide. Boc migration from the neighboring phenol produced a magnesium phenoxide that we supposed underwent β-elimination of the transferred Boc residue to form an o-QM for immediate further reactions. Moreover, the cascade proved controllable through careful manipulation of metallic and temperature levers so that it could be paused, stopped, or restarted at various intermediates and stages. This new level of domestication enabled us to deploy o-QMs for the first time in a range of applications including diastereocontrolled reactions.This sequence ultimately could be performed in either multipot or single pot processes. The subsequent reaction of the fleeting o-QM intermediates included the 1,4-conjugate additions that led to unbranched or branched ortho-alkyl substituted phenols and Diels–Alder reactions that provided 4-unsubstituted or 4-substituted benzopyrans and chroman ketals. The latter cycloadducts were obtained for the first time with outstanding diastereocontrol. In addition, the steric effects of the newly created stereocenters in subsequent reactions of chroman ketals and acetals were studied and proved predictable. Through the use of a chiral auxiliary, Diels–Alder products were deployed in numerous enantioselective reactions including several complex natural products syntheses. In this Account, we summarize our efforts, which we hope have contributed to the synthetic renaissance for this venerable species.

We report the synthesis of diinsininone (33), the aglycone of (±)-diinsinin (2). Thereby, we complete the first construction of a proanthocyanidin (PA) type-A compound incorporating a [3.3.1]-bicyclic ketal as its characteristic core. Our strategy utilizes a coupling between a benzopyrilium salt and a flavanone that proves applicable to other PA type-A compounds. During this undertaking, treatment of naringenin (9) with 2-iodoxybenzoic acid (IBX) followed by reductive work-up affords eriodictyol (10). This reactivity mirrors that of catechol hydroxylase (F3H) found in the flavonoid pathway. Other interesting transformations include the formation of flavonoids through an ortho-quinone methide (o-QM) cycloaddition-oxidation sequence and regioselective β-glycosidations of several unprotected flavanones suggesting a likely synthesis of 2 from the aglycone 33.