Synthesis of a Diaryliodonium Salt and Its Use in the Direct Arylation of Indole: A Two-Step Experiment for the Organic Teaching Laboratory

In the past decade, C-H functionalization has been a very active topic of research in both academia and industry. When a H atom is replaced by an aryl (or heteroaryl) group, the transformation is termed "direct arylation". This approach to the formation of key (hetero)aryl-(hetero)aryl bonds is complementary to traditional methods, such as the Suzuki-Miyaura and Stille reactions. Direct arylation/C-H functionalization is not represented in the majority of undergraduate chemistry laboratory curricula. An experiment is described here in which students carry out a multistep process, synthesizing a diaryliodonium salt and using it in the direct arylation of indole. Important organic and organometallic chemistry concepts are covered, including catalysis, traditional cross-coupling, C-H functionalization, multistep reaction processes, and regioselectivity. The experiment was successfully carried out by third- and fourth-year students in two universities over a two-year period (four times in total). Both high-yielding and low-yielding chemical steps were encountered, and a number of pedagogical approaches evolved.