Room Temperature, Metal-Free Synthesis of Diaryl Ethers with Use of Diaryliodonium Salts

Abstract

Diaryl ethers are common structural features in numerous natural products and biologically active compounds. Despite more than a century of immense focus on finding efficient synthetic routes to this compound class, diaryl ethers remain difficult to obtain. Routes that are catalytic in copper have been developed, but high catalyst loadings, excess reagents, elevated temperatures and long reaction times are still needed. Pd-catalyzed cross-couplings of phenols and aryl halides at temperatures up to 100 °C have recently been reported to give high yields of diaryl ethers. Diaryliodonium salts are non-toxic alternatives to transition metals in the synthesis of diaryl ethers and we have recently developed effective synthetic routes to these salts.Herein we report a fast, high-yielding synthesis of diaryl ethers. The reaction conditions are mild, metal-free, and avoid the use of halogenated solvents, additives, or excess reagents. Precautions to avoid air or moisture are not needed. The scope includes ortho-and halo-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols . Monday,

Copper(II)‐Catalyzed Monoarylation of Vicinal Diols with Diaryliodonium Salts

“…[9] While the cross-coupling reaction of phenol derivatives with diA C H T U N G T R E N N U N G aryl-A C H T U N G T R E N N U N G iodonium salts has been known as an effective synthetic method towards diaryl ethers, [10,11] the synthesis of alkyl-aryl ethers with diaryliodonium salts requires an excess of alkoxides. [12] We envisaged that diaryliodonium salts could achieve high efficiency in the C À O bond formation with diols and the coupling of alcohols with this type of reagents has not been widely explored.…”

Diaryliodonium Salts in Organic Syntheses: A Useful Compound Class for Novel Arylation Strategies

“…In 2011, they reported an O-arylation procedure for the preparation of diaryl ethers (4) from phenols (3) under mild conditions in short reaction time (Scheme 3). 14 The products were isolated in 72-99% yields with a number of diaryliodonium salts containing tetrafluoroborate or triflate anion. Sterically crowded, ortho-substituted phenol derivatives were also transformed to the desired products.…”

Synthesis of New Chiral Diaryliodonium Salts

“…Indeed, no racemisation was observed after hydrolysis of the methoxymethyl ester (ee >99%, as determined by chiral HPLC). Arylation with diphenyliodonium triflate 25 or alkylation with iodomethane provided model systems 12a and 12b to study the oxidation and salt forming steps.…”