Phenols, anilines, and malonates have been arylated under metal-free conditions with twelve aryl(phenyl)iodonium salts in a systematic chemoselectivity study. A new “anti-ortho effect” has been identified in the arylation of malonates. Several “dummy groups” have been found that give complete chemoselectivity in the transfer of the phenyl moiety, irrespective of the nucleophile. An aryl exchange in the diaryliodonium salts has been observed under certain arylation conditions. DFT calculations have been performed to investigate the reaction mechanism and to elucidate the origins of the observed selectivities. These results are expected to facilitate the design of chiral diaryliodonium salts and the development of catalytic arylation reactions that are based on these sustainable and metal-free reagents.

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,

Phenols and carboxylic acids are efficiently arylated with diaryliodonium salts. The reaction conditions are mild, metal free, and avoid the use of halogenated solvents, additives, and excess reagents. The products are obtained in good-to-excellent yields after short reaction times. Steric hindrance is very well tolerated, both in the nucleophile and diaryliodonium salt. The scope includes ortho- and halo-substituted products, which are difficult to obtain by metal-catalyzed protocols. Many functional groups are tolerated, including carbonyl groups, heteroatoms, and alkenes. Unsymmetric salts can be chemoselectively utilized to obtain products with hitherto unreported levels of steric congestion. The arylation has been extended to sulfonic acids, which can be converted to sulfonate esters by two different approaches. With recent advances in efficient synthetic procedures for diaryliodonium salts the reagents are now inexpensive and readily available. The iodoarene byproduct formed from the iodonium reagent can be recovered quantitatively and used to regenerate the diaryliodonium salt, which improves the atom economy.

Diaryliodonium salts are demonstrated as efficient arylating agents of aliphatic alcohols under metal-free conditions. The reaction proceeds at room temperature within 90 min to give alkyl aryl ethers in good to excellent yields. Aryl groups with electron-withdrawing substituents are transferred most efficiently, and unsymmetric iodonium salts give chemoselective arylations. The methodology has been applied to the formal synthesis of butoxycaine.

PostprintThis is the accepted version of a paper published in Tetrahedron. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. Design and asymmetric synthesis of chiral diaryliodonium salts

This is the accepted version of a paper published in Tetrahedron Letters. This paper has been peerreviewed but does not include the final publisher proof-corrections or journal pagination.

One-pot synthesis of diaryliodonium salts using toluenesulfonic acid -a fast entry to electronrich diaryliodonium tosylates and triflates. Abstract: A direct synthesis of symmetric and unsymmetric electron-rich diaryliodonium salts is described. The use of mCPBA and toluenesulphonic acid delivers diaryliodonium tosylates in high yields. An in situ anion exchange has also been developed, giving access to the corresponding triflate salts. Synlett: Accounts and Rapid Communications in Synthetic Organic

3‐Iodobenzotrifluoride p ‐Toluenesulfonic acid monohydrate m ‐Chloroperbenzoic acid 2,2,2‐Trifluoroethanol 1‐[Hydroxy(tosyloxy)iodo]‐3‐trifluoromethylbenzene