A revised bonding model for diarylhalonium salts, that involves partial s-orbital contribution, provides new insight into periodic trends in structure and reactivity.

Arenes are broadly found motifs in societally important molecules. Access to diverse arene chemical space is critically important, and the ability to do so from common reagents is highly desirable. Aryl(TMP)iodonium tosylates provide one such access point to arene chemical space via diverse aryl intermediates. Here we demonstrate that controlling reaction pathways selectively leads to arynes with a broad scope of arenes and arynophiles (24 examples, 70% average yield) and efficient access to biologically active compounds.

Arynes offer immense potential for diversification of benzenoid rings, which occur in pharmaceuticals, agrochemicals, and liquid crystals. However, accessing these high-energy intermediates requires synthetic precursors, which involve either harsh conditions or multistep syntheses. The development of alternative methods to access arynes using simpler substrates and milder conditions is necessary for a more streamlined approach. Here, we describe a two-step formal dehydrogenation of simple arenes to generate arynes at a remote position relative to traditionally reactive groups, e.g., halides. This approach is enabled by regioselective installation and ejection of an “onium” leaving group, and we demonstrate the compatibility of simple arenes (20 examples) and arynophiles (8 examples). Moreover, through direct comparison, we show that our formal dehydrogenation method is both more functional group tolerant and efficient in generating arynes than the current state-of-the-art aryne precursors. Finally, we show that aryne intermediates offer opportunities for regioselective C–H amination that are distinct from other methods.

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. Greater 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.

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 aryne precursors has stymied their widespread use. Here, we show that generating arynes can be both efficient and mild by deprotonating aryl(TMP)iodonium salts with potassium phosphate (TMP = 2,4,6-trimethoxyphenyl) and these conditions are uniquely compatible with acyclic diaryliodonium salts. We have also performed the first comparison of functional group compatibility by the method of additives across a range of reaction conditions, including the current state-of-the-art, to generate arynes. The scope of the reaction conditions includes sensitive functional groups such as benzylic halides, ketones, alcohols, and boronate esters that are not compatible with prior methods and charts a new course forward for aryne chemistry.