Phenol-arene cross-coupling

Phenol-Arene Cross-Coupling and Nonsymmetrical Coupling Products... 

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 selective electrochemical oxidation of one reaction partner gave rise to the first anodic phenol-arene cross-coupling (Scheme 4) [4]. The presence of additional water or methanol in the electrolyte turned out to be beneficial for the yield as well as selectivity [18]. In many cases, the ratio for the mixed biaryl (AB) vs. biphenyl (BB) exceeded 100 1. Since no leaving functionalities are required, simple starting materials can be employed, and the 1,1,1,3,3,3-hexafluoroisopropanol is almost quantitatively recovered. Biaryls 8-10 with different substitution patterns are feasible in good isolated yields. The transformation is compatible with a variety of functional groups and tolerates sulfide and tertiary alkyl moieties in the substrates. Compound 11 and 12 were the only observed mixed biaryls in the reaction mixture. Products originating... 

The observed chemoselectivity is unique. Anodic treatment on BDD of 3,4,5-trimethoxy toluene results in the exclusive formation of the mixed biaryl 56. This method can be further performed with benzo[l,3]dioxole-containing arenes as reaction partners, giving biaryls 57 and 58 in acceptable yields. Furthermore, naphthalene moieties can be directly located onto 4-methyl guaiacol as the products 59 and 60 reveal. This novel cross-coupling can be expanded to other phenolic reaction partners as well [28]. The displayed selection of mixed biaryls 53-60 is accessible in a single step. In the workup protocol, HFIP is almost quantitatively recovered since it represents the most volatile component in the electrolyte. In addition, nonconverted starting materials can be recycled by short path distillation with approximately 80% efficiency (Scheme 23). 

The ready availability of arylboronates by an aromatic C-H borylation provides a synthetic link to the well-established palladium-catalyzed cross-coupling reactions, rhodium-catalyzed 1,4-addition to a,p-unsaturated carbonyl compounds, and other bond forming reactions using arylboronic esters (Scheme 2.12). Borylation of 1,3-dichlorobenzene with pinacolborane is followed directly by a cross-coupling reaction with methyl p-bromobenzoate for the synthesis of a biaryl product in 91% yield [60]. Pinacol esters of arylboronic acids react much slower than the free acids [62], but both derivatives achieve high isolated yields and comparable enantioselectivities (91% ee) in asymmetric 1,4-addition to N-benzyl crotonamides [63]. Borylation of arenes followed by oxidation of the C-B bond is synthetically equivalent to an aromatic C-H oxidation to phenols [64]. Oxidation of the resulting arylboronates with Oxone in a 1 1 acetone-water solution is completed within 10 min at room temperature. 

In addition to the synthesis of phenols through metal-catalyzed cross-coupling chemistry between aryl halides and hydroxide sources, the C—H hydroxylation of arenes has also been used to prepare phenols. This is an attractive approach to the synthesis of these valuable compounds since it does not require prior functionalization of the arene. 

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