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.
A novel catalytic system for oxidative cross-coupling of readily oxidized phenols with poor nucleophilic phenolic partners based on an iron meso-tetraphenylporphyrin chloride (Fe[TPP]Cl) complex in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) was developed. The unique chemoselectivity of this reaction is attributed to the coupling between a liberated phenoxyl radical with an iron-ligated phenolic coupling partner. The conditions are scalable for preparing a long list of unsymmetrical biphenols assembled from a less reactive phenolic unit substituted with alkyl or halide groups.
The iron-catalyzed oxidative coupling
of phenols has emerged as
a powerful method for preparing complex phenolic frameworks from simple
and readily available compounds. This synopsis describes the selectivity
challenges inherent in oxidative coupling reactions while at the same
time presents our mechanistic-driven strategy employed to confront
them.
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 selectivity-driven
catalyst design approach was adopted to address
chemoselectivity issues in the oxidative coupling of phenols. This
approach was utilized for developing a Co(II)[salen]-catalyzed aerobic
oxidative cross-coupling of phenols in a recyclable 1,1,1,3,3,3-hexafluoropropan-2-ol
(HFIP) solvent. The waste-free conditions offer a sustainable entry
to nonsymmetric biphenols via a mechanistic scheme that involves coupling
of a liberated phenoxyl radical with a ligated 2-naphthoxyl radical.
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