Synthesis of Diaryl Ethers: A Long-Standing Problem Has Been Solved

Abstract

A breakthrough in the synthesis of diaryl ethers has been achieved as shown in Equation (1). The coupling of phenols with aryl boronic acids in the presence of copper(II) acetate and a base proceeds under very mild conditions (room temperature) as described simultaneously by Evans et al. and Chan et al. Examples: R(1)=2-Cl, 2-I, 2-OMe, 4-tBu, 4-CH(2)CH(NHCOOtBu)CO(2)Me, 3,5-tBu(2); R(2)=2-Me, 3-OMe, 3-NO(2), 4-H, 4-F, 4-OMe.

Tris-(2-aminoethyl) amine as a novel and efficient tripod ligand for a copper(I)-catalyzed C–O coupling reaction

“…1 This structural unit is prevalent in commercially relevant polypropylene polymers and numerous pesticides. 2 They are extremely versatile intermediates of medicinally active compounds such as Vancomycin, Piperazinomycin (antifungal), K-13 (ACE inhibitor) and others. 3 Conventionally, diaryl ethers are produced by Ullmann condensation 4 of aryl halides and phenols with copper in the form of a metal salt.…”

Aryl Carbon–Heteroatom Coupling Reactions Using Nanometal Catalyst

“…Formation of aryl C O bonds is important as diaryl ethers are structural motifs in a large number of natural products, industrial polymers, and biologically active compounds (Figure 6.3). [29][30][31][32][33][34][35][36][37][38] The most common and useful procedure for the preparation of diaryl ethers is the transitional metal-catalyzed coupling of aryl halides and phenols. Palladium has been widely used for this reaction with high efficiency; however, the high cost of palladium and the use of expensive ligands limit its industrial application.…”

Aminoarenethiolato-copper(I) as (pre-)catalyst for the synthesis of diaryl ethers from aryl bromides and sequential C–O/C–S and C–N/C–S cross coupling reactions

“…2 This structural moiety is part of various important pharmaceuticals with antibiotic activity, such as vancomycin, 3 teicoplanin, 4 the antiviral peptide K-13, 5 the antitumoral bouvardin 6 and many others. 7 Common routes for the preparation of these ethers, i.e., through CeO bond formation, involve the classical Ullmann diaryl synthesis, 8 which however has several drawbacks related to harsh reaction conditions and stoichiometric use of the copper mediator.…”