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Abstract Diaryliodonium salts continue to emerge as versatile arylation reagents. This is especially true for unsymmetrical aryl(TMP)iodonium salts (TMP = 2,4,6-trimethoxyphenyl) because they undergo highly selective aryl transfer across diverse mechanistic settings. This account outlines our motivation for exploring the chemistry of aryl(TMP)iodonium salts and our efforts to develop streamlined synthetic methods to access them and the novel arylation reactions that use them. 

Arynes are versatile intermediates for organic synthesis and now they can be accessed from arenes in one or two-pot sequencesviaaryl thianthrenium (in situ) and aryl iodonium (isolated) intermediates, respectively. 

Diaryliodonium-amine complexes are proposed as key intermediates in C–N coupling reactions. The Lewis basicity of synthetically relevant amines are quantified on the Legault iodonium Lewis acidity scale. 

Abstract We describe the development of a C–O coupling reaction between aryl(2,4,6-trimethoxyphenyl)iodonium salts and aliphatic alcohols under weak base conditions. The scope of the reaction is presented, with 16 examples ranging in yield from moderate to high (54–96%). The limitations of the reaction are also presented. Mechanistic experiments reveal a complex network of reactions that include side reactions that generate arynes and oxidize the alcohol nucleophile. 

Halogen bonding permeates many areas of chemistry. A wide range of halogen-bond donors including neutral, cationic, monovalent, and hypervalent have been developed and studied. In this work we used density functional theory (DFT), natural bond orbital (NBO) theory, and quantum theory of atoms in molecules (QTAIM) to analyze aryl halogen-bond donors that are neutral, cationic, monovalent and hypervalent and in each series we include the halogens Cl, Br, I, and At. Within this diverse set of halogen-bond donors, we have found trends that relate halogen bond length with the van der Waals radii of the halogen and the non-covalent or partial covalency of the halogen bond. We have also developed a model to calculate ΔGof halogen-bond formation by the linear combination of the % p-orbital character on the halogen and energy of the σ-hole on the halogen-bond donor. 

Arynes hold immense potential as reactive intermediates in organic synthesis as they engage in a diverse range of mechanistically distinct chemical reactions. However, the poor functional group compatibility of generating arynes or their precursors has stymied their widespread use. Here, we show that generating arynes by deprotonation of an arene and elimination of an “onium” leaving group is mild, efficient and broad in scope. This is achieved by using aryl(TMP)iodonium salts (TMP = 2,4,6-trimethoxyphenyl) as the aryne precursor and potassium phosphate as the base, and a range of arynophiles are compatible. Additionally, we have performed the first quantitative analysis of functional group compatibility for several methods to generate arynes, including the method developed here and the current state of the art. Finally, we show that a range of “sensitive” functional groups such as Lewis and Brønsted acids and electrophiles are compatible under our conditions. 

Arylboron compounds are widely available and synthetically useful reagents in which the boron group is typically substituted. Herein, we show that the boron group and orthohydrogen atom are substituted in a formal cycloaddition reaction. This transformation is enabled by a one-pot sequence involving diaryliodonium and aryne intermediates. The scope of arylboron reagents and arynophiles is demonstrated, and the method is applied to the formal synthesis of an investigational drug candidate. 

Abstract Arynes are highly reactive intermediates that may be used strategically in synthesis by trapping with arynophilic reagents. However, ‘arynophilicity’ of such reagents is almost completely anecdotal and predicting which ones will be efficient traps is often challenging. Here, we describe a systematic study to parameterize the arynophilicity of a wide range of reagents known to trap arynes. A relative reactivity scale, based on one-pot competition experiments, is presented by using furan as a reference arynophile and 3-chlorobenzyne as a the aryne. More than 15 arynophiles that react in pericyclic reactions, nucleophilic addition, and σ-bond insertion reactions are parameterized with arynophilicity (A) values, and multiple aryne precursors are applicable.