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. 2025 May 9;27(18):4782-4787.
doi: 10.1021/acs.orglett.5c01266. Epub 2025 Apr 30.

Quinol-Enedione Rearrangement

Tomás Vieira de Castro  1 , François Richard  1 , Steven H Bennett  1 , Caspar S Lamborelle  1 , Gary S Nichol  1 , Rafał Szabla  2   3 , Andrew L Lawrence  1
Affiliations

Quinol-Enedione Rearrangement

Tomás Vieira de Castro et al. Org Lett. .

Abstract

The quinol-enedione rearrangement enables the synthesis of 2-cyclohexene-1,4-diones from readily available para-quinol substrates. Building on sporadic early reports of this transformation, we have optimized the reaction conditions and systematically investigated its substrate scope. The utility of Brønsted acid-mediated reaction conditions for a variety of quinol derivatives, including those with substituted and unsubstituted migrating termini, is highlighted. Notably, kinetic selectivity between quinol-enedione and dienone-phenol rearrangements is demonstrated. The synthetic potential of the enedione products is showcased through a range of transformations, leading to the formation of complex polycyclic structures. These findings provide a valuable framework for recognizing and applying the quinol-enedione rearrangement in synthesis, while computational studies offer valuable insights into its mechanistic underpinnings.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Dienone–Phenol and Quinol–Enedione Rearrangements, Shown Proceeding via Brønsted Acid Catalyzed Mechanisms
Scheme 2
Scheme 2. Davis’ Seminal Quinol–Enedione Rearrangement and Representative Natural Products That Contain the Enedione Framework
Scheme 3
Scheme 3. Substrate Scope for the Quinol−Enedione Rearrangement
Scheme 4
Scheme 4. Investigating Selectivity between Quinol–Enedione and Dienone–Phenol Rearrangements
1.0 equiv of p-TsOH used.
Scheme 5
Scheme 5. Failed Substrates for the Quinol–Enedione Rearrangement
Scheme 6
Scheme 6. Derivatization Studies on Model Enedione 2a
23% yield of the diketone formed from hydrolysis of enol acetate 15 was also isolated.
See this image and copyright information in PMC

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