An iron-catalyzed oxidative unsymmetrical biphenol coupling in 1,1,1,3,3,3-hexafluoropropan-2-ol that proceeds via a chelated radical-anion coupling mechanism was developed. Based on mechanistic studies, electrochemical methods, and density functional theory calculations, we suggest a general model that enables prediction of the feasibility of cross-coupling for a given pair of phenols.

Significant enhancement of both the rate and the chemoselectivity of iron-catalyzed oxidative coupling of phenols can be achieved in fluorinated solvents, such as 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP), 2,2,2-trifluoroethanol (TFE), and 1-phenyl-2,2,2-trifluoroethanol. The generality of this effect was examined for the cross-coupling of phenols with arenes and polycyclic aromatic hydrocarbons (PAHs) and of phenol with β-dicarbonyl compounds. The new conditions were utilized in the synthesis of 2'''-dehydroxycalodenin B in only four synthetic steps.

A bioinspired iron-catalyzed consecutive oxidative cross-coupling reaction between a single phenolic unit and nucleophilic arenes was developed. This sustainable transformation offers a selective synthetic strategy for the preparation of complex polyaryl compounds directly from readily available phenols. With the aid of electron paramagnetic resonance spectroscopy, it was demonstrated that the groups ortho to the phenolic functionality (whether hydrogen, methyl, or methoxy) direct the regioselectivity (ortho, para, or meta via dienone-phenol rearrangement) and chemoselectivity (C-C coupling or C-O coupling) in this multistep process.

Significant enhancement of both the rate and the chemoselectivity of iron-catalyzedo xidative coupling of phenols can be achieved in fluorinated solvents,such as 1,1,1,3,3,3hexafluoropropan-2-ol (HFIP), 2,2,2-trifluoroethanol (TFE), and 1-phenyl-2,2,2-trifluoroethanol. The generality of this effect was examined for the cross-coupling of phenols with arenes and polycyclic aromatic hydrocarbons (PAHs) and of phenol with b-dicarbonyl compounds.T he new conditions were utilized in the synthesis of 2'''-dehydroxycalodenin Bi n only four synthetic steps.

Synthetic and Predictive Approach to Unsymmetrical Biphenols by Iron--Catalyzed Chelated Radical-Anion Oxidative Coupling. -An interesting cross coupling of two different phenols is achieved in the presence of FeCl 3 as catalyst in hexafluoroisopropanol as solvent to give the unsymmetrical biphenol coupling products. -(LIBMAN, A.; SHALIT, H.; VAINER, Y.; NARUTE, S.; KOZUCH, S.; PAPPO*, D.; J. Am. Chem. Soc. 137 (2015) 35, 11453-11460, http://dx.doi.org/10.1021/jacs.5b06494 ; Dep. Chem., Ben-Gurion Univ. Negev, Beer Sheva 84105, Israel; Eng.) -Mais 10-044

Phenols and naphthols are regioselectively coupled with 2‐oxocyclopentanoic acid ester (II), arenes (IV) and (VII), polyaromatic hydrocarbons, e.