Metal-free oxidative aromatization of 2-aryloxycyclohex-2-en-1-ones to 2-aryloxyphenols using DDQ/Amberlyst-15

Abstract

Efficient metal-free oxidative aromatization of 2-aryloxycyclohex-2-en-1-ones was achieved by a combination of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and Amberlyst-15. The conditions for oxidative aromatization are mild and applicable for a variety of substrates, and Amberlyst-15 can be successfully recovered and recycled. 2-Aryloxyphenols constitute an important structural motif in medicinal chemistry, which shows a wide spectrum of therapeutic applications. For example, 2-phenoxyphenol (I) and Triclosan (II) are antibacterial drugs [1], while 2-aryloxyphenol containing biologically active peptides viz. vancomycin family member isodityrosine (III) [2], K-13, [3] OF-4949-I-IV [4], Bouvardin [5], and RA I-IV [6] exhibit antitumor activity. Besides these important applications, 2-aryloxyphenols are important building blocks for the synthesis of polycyclic furans like IV [7].above methods suffer from such drawbacks as the use of metals, high temperatures, complex reaction systems, poor yields, and limited scope of substrates.Oxidative aromatization of cyclohexenones to phenols is an important transformation in organic synthesis, so metal-free oxidative aromatization is highly desirable. The best choice of reagents for oxidative aromatization of substituted cyclohexenones would be iodine and DDQ (2,3-dichloro-5,6-dicyano-p-benzoquinone). However, oxidative aromatization of substituted cyclohexenones with iodine in methanol afforded directly aryl phenyl ethers instead of 2-aryloxyphenols [17]. DDQ has been investigated as a powerful oxidant by several research groups [18] and was proved to be useful for a wide range of reactions. This prompted us to use DDQ for oxidative aromatization of 2-aryloxycyclohex-2-en-1-ones to 2-aryloxyphenols. DDQ can be activated by Brønsted acids like concd. HCl, concd. H 2 SO 4 , and TsOH, but these acids are corrosive. Replacement of these acids by solid acids is always desirable.Herein we report for the first time the use of a combination of DDQ and a solid acid, Amberlyst-15, for efficient and metal-free oxidative aromatization of 2-aryloxycyclohexenones to 2-aryloxyphenols. Amberlyst-15 has been recovered and recycled successfully. The reaction conditions are mild, and 2-aryloxyphenols are obtained in good yield. 2-Aryloxycyclohex-2-en-1-ones Va-Vj were prepared by ring opening of 2,3-epoxycyclohexanone with phenols using K 2 CO 3 in acetonitrile under reflux.Oxidative aromatization was attempted in the presence of various well known oxidants. Oxidative aro-

Visible Light Photocatalysis of 6π Heterocyclization

“…[11] This principle has been elegantly applied to the energy transfer mediated [2+ +2] cycloaddition of olefins [12] and other processes. [13] Consequently,w ep repared at est 2aryloxyketone substrate 1a through treatment of the epoxide derived from 3-methylcyclohexenone with phenol in the presence of potassium carbonate in acetonitrile, [14] and examined its reactivity in the presence of ar ange of photocatalysts under irradiation with blue LED light ( Table 1). [15] Ruthenium(II) catalysts proved to be ineffective (entries 1a nd 2), [16] and hence we examined photocatalysts with significantly higher triplet energies.…”

UV-light induced domino type reactions: synthesis and photophysical properties of unreported nitrogen ring junction quinazolines

“…31 Many literature reports record either the synthesis of ring junction nitrogen compounds without aromatization or two step procedures were necessary to get the aromatized ring junction nitrogen compound. [32][33][34] To aromatize the compound, DDQ 35 /toluene, PhCl/p-chloranil 36 or CAN/ acetone 37 were used. However, these methodologies require a longer time for the completion of the reaction and provide a lower yield.…”

Tandem Thien- and Benzannulations of α-Alkenoyl-α-alkynyl Ketene Dithioacetals with Cyanoacetates: Synthesis of Functionalized Benzo[b]thiophenes

“…Subsequently, Michael addition of the anion of ethyl 2-cyanoacetate to the double bond of 4 followed by protonation formed intermediate IV . Deprotonation of IV triggered an intramolecular nucleophilic displacement of the labile thioether furnishing VII , which underwent ester elimination followed by oxidative aromatization to produce the desired benzo­[ b ]­thiophenes 2 . Existence of intermediates IV and VII were supported by HRMS analysis…”