Adding nitrogen beads to indole bracelets

The joy (and pain) of teaching undergraduate organic chemistry escalates when grading exams. In particular, being asked to propose plausible sequences to synthesise target compounds prompts some students to suggest many bold ideas. In their answer sheets, important selectivity issues, such as chemoselectivity (preferentially transforming one functional group over another) and regioselectivity (preferentially functionalising one position over another), are sidelined in a rush to obtain the final products. Acyclic carbon chains easily decrease or increase in length without due cause. However, even the most hasty students remain cautious about reducing and enlarging ring sizes, particularly in the case of heteroaromatic rings, which are notoriously very difficult to transform.

In fact, developing a simple way to transform heteroarenes to another class of heteroarenes is high on the wish lists of many organic chemists. Heteroarenes are ubiquitous in drug discovery as their size, shape and electronic properties vary widely and they enable molecular interactions such as hydrogen bonding and π-π interactions. Therefore, chemists carefully select heterocyclic cores, as well as the type and position of the functional groups bound to them, to provide exquisite control over drug–target interactions and physicochemical properties.