Access to arynes from arenes via net dehydrogenation: scope, synthetic applications and mechanistic analysis

Abstract

Arynes undergo a wide range of chemical transformations making them versatile reactive intermediates for organic synthesis. Access to arynes has long been dominated by pre-functionalised reagents, e.g., the venerable o-trimethylsilylaryl triflates. However, a move toward developing methods to access arynes that are both mild and efficient has prompted research into aryl “onium” aryne precursors. Here, we leverage aryl “onium” species as in situ or isolated intermediates in a net dehydrogenation of simple arenes as a novel and efficient way to access arynes. We describe a unified strategy in which two different tactics are employed to access diversely substituted arynes from simple arenes. 1) We developed a one-pot method that converts simple arenes into aryl thianthrenium salts and uses them in situ to generate arynes. 2) We developed a two-step process to convert arenes into aryl(Mes)iodonium salts and ultimately trapped arynes to expand the scope of compatible arenes. The net transformations from arenes to trapped arynes are complete with 2-4 hours. Mechanistic analysis through competition experiments, deuterium kinetic isotope effects (DKIE) and Density Functional Theory (DFT) provide key comparisons of the two approaches described in this work and yield a user’s guide for selecting the appropriate “onium” leaving group based on the arene.