Cross coupling reactions phenols

Novel heteroquaterphenoquinones were synthesized by a stepwise cross-coupling reaction or by a more convenient one-pot oxidative homocoupling reaction of the heterocycle-substituted phenols (Scheme 20, <96JOC4784 see also 95TL8055>). 

The use of enol- and phenol-esters in cross-coupling reactions is a valuable protocol, as it gives an indirect way to involve readily available phenols and carbonyl compounds as the electrophilic components of cross-couplings (Equation (22)) ... 

Disubstituted 4-chloro-2-cyclobutenones 75 undergo the palladium-catalyzed cross-coupling reaction with vinyl- and arylstannanes 76 or vinylzir-conium reagents to give the 4-R sa,-2-cyclobutenones 77. Without isolation, these cyclobutenones 77 are rearranged to the substituted phenols 78 on thermolysis [38], Application of this method to the stannylated heteroaromatics 79 provides a synthetic route to the aromatic benzoheterocycles 80 [39]. (Scheme 27 and 28)... 

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

The 4- and 6-positions of pyrrolo[2,3-3]pyridines can be substituted via palladium-catalyzed cross-coupling reactions with the 4- or 6-halo-substituted derivatives (Scheme 3) <2001SL609>. Nucleophilic displacement of the 4-substituent of 6-chloro-4-nitro- and 4,6-dichloro-pyrrolo[2,3-/ ]pyridines takes place with phenols. Protection of the pyrrole nitrogen with a /3-trimethylsilylethoxymethyl (SEM) group affords good yields of the aryl ethers (Equation 3) <2006TL2069>. 

We recently reported the synthesis of a perfluoroalkylsulfonyl linker attached to TentaGel resin 13 (Fig. 6), which proves to act in a fashion similar to triflates as we had hoped, and demonstrated its application for the traceless cleavage of phenols using palladium-catalyzed reduction and Suzuki cross-coupling reactions.3,4... 

Saa, J. M. Martorell, G. Garda-Raso, A. Palladium-catalyzed cross-coupling reactions of highly hindered, electron-rich phenol triflates and organostannanes./. Org. Chem. 1992, 57, 678-685. 

Kirste A, Schnakenburg G, Stecker F, Fischer A, Waldvogel SR (2010) Anodic phenol-arene cross-coupling reaction on boron-doped diamond electrodes. Angew Chem Int Ed 49 971-975... 

The Suzuki cross-coupling reaction is recognized as a novel, abbreviated method for the synthesis of 2-hydroxychrysene, 2-hydroxy-5-methylchrysene, and 8-hydroxy-5-methyl-chrysene from easily accessible reactants (Eq. (8)) [23]. These phenolic compounds constitute precursors for the synthesis of dihydrodiol and bay-region diol epoxide derivatives of chrysene and 5-methylchrysene, which are implicated as the active forms of carcinogenic polynuclear aromatic hydrocarbons. 

Using peroxidases in the presence of hydrogen peroxide, phenolic substrates are converted catalytically to phenoxy radicals (Fig. 8.1). The phenoxy radicals produced in the enzymatic reaction step can then, in postenzymatic reactions, couple with each other or with other reactive substances present in the system [28-32]. Self-coupling of phenol molecules with each other dominates in systems that lack appropriate substrates to participate in cross-coupling reactions with phenol, leading to formation of precipitated polymeric products [9, 33] that can be readily removed from water. 

Finally, ortho- 2,2-dibromovinyl)-aniline or -acetanilide can successfully be applied in a sequential cyclizing amination-cross coupling reaction with diethyl phosphonate to furnish the indolyl phosphonic ester 136 or the N-acetyl 2-aryl indole 137 as recently shown by Bisseret and coworkers [ 105] (Scheme 50). This sequence can be also performed with corresponding phenol derivatives furnishing benzofurans. For the N-acetyl 2-aryl indole 137 it can be shown that the Suzuki coupling occurs prior to the intramolecular animation as a consequence of the gradual difference in reactivity between trans-and czs-carbon-bromine bonds. 

When two different phenols having almost the same oxidation potentials are used, both dimerization and cross-coupling reactions may take place. Coniferyl alcohol (298) was first oxidized alone with H2O2, catalyzed by horseradish peroxidase (HRP) in a 20% buffer solution (pH 3.5) in acetone (room temp., 1 h) to afford three dimers (301, 302 and 303) in 12, 24 and 16% yields, respectively, as shown in Scheme 65, wherein the remaining starting phenol (36%) was further oxidized to ohgomers (12%). In the case of a 1 1 mixture of 298 and apocynol (304), small amounts of cross-coupled products (305 and 306) were obtained in 5-10 and 0-1.5% yields, respectively, in addition to four dimers (301, 302, 303 and 307). Here, 45% of 304 remained (Scheme 65). On chemical oxidation of a 1 1 mixture of 298 and 304 with Mn(OAc)3 in AcOH (room temp., 30 min), the yield of 305 increased to 18%. 

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