Herein, we describe a synthetic approach for arylation that exploits the in situ formation and reaction of an unsymmetrical diaryliodonium salt. In this way, aryl iodides are used as reagents in a metal-free reaction with phenols, and a trimethoxyphenyl (TMP) group is used as a "dummy" group to facilitate transfer of a wide range of aryl moieties. The scope of aryl electrophiles and phenol nucleophiles is broad (> 30 examples) and the yields are high (52-95%, 80% avg.). One-pot coupling reactions avoid the synthesis of diaryliodonium salts and provide opportunities for sequential reactions and novel chemoselectivity.

The endochin-like quinolone (ELQ) compound class may yield effective, safe treatments for a range of important human and animal afflictions. However, to access the public health potential of this compound series, a synthetic route needed to be devised, which would lower costs and be amenable to large-scale production. In the new synthetic route described here, a substituted β-keto ester, formed by an Ullmann reaction and subsequent acylation, is reacted with an aniline via a Conrad–Limpach reaction to produce 3-substituted 4­(1H)-quinolones such as ELQ-300 and ELQ-316. This synthetic route, the first described to be truly amenable to industrial-scale production, is relatively short (five reaction steps), does not require palladium, chromatographic separation, or protecting group chemistry, and may be performed without high vacuum distillation.

Herein, we describe the discovery and development of a method to exchange the counteranion component of diaryliodonium salts, which is a critical step for their use in chemical synthesis. The method involves a reusable and readily available solid-phase column assembled from common laboratory consumables. This process avoids challenging product separation associated with other methods for anion metathesis of diaryliodonium salts, and selected examples demonstrate the scope of the method. Hazard analysis (differential scanning calorimetry) on all salts used in this study revealed exotherm initiation temperature in the range of 139−199 °C and exotherm magnitude of 60−845 J/g for a single peak.

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