Electrochemical oxidation of 3-substituted indoles

2-Oxindoles are an abundant heteroaromatic motif in natural products and pharmaceuticals. An appealing method for accessing 2-oxindoles is by oxidation of the corresponding indole, a transformation currently executed using stoichiometric quantities of unsafe chemical oxidants that can also form unwanted side-products. Herein, we report that 3-substituted indoles undergo a logistically straightforward, electrochemical oxidation to the corresponding 2-oxindole in the presence of potassium bromide (>20 examples), with only traces of the oxidative dimer detected. Cyclic voltammetry and control studies infer that the reaction proceeds by electrochemical generation of elemental bromine (Br-2) that upon reaction with indole, followed by hydrolysis, delivers the 2-oxindole. This procedure is an appealing alternative to existing methods used to access 2-oxindoles by oxidation of the parent indole.

Automated summary

2-Oxindoles are commonly found heteroaromatic motifs in natural products and pharmaceuticals. A feasible method for synthesizing 2-oxindoles is by oxidizing the corresponding indoles, which currently involves the use of stoichiometric amounts of unsafe chemical oxidants and can lead to the formation of unwanted by-products. In this study, we found that 3-substituted indoles can be electrochemically oxidized to the corresponding 2-oxindoles in the presence of potassium bromide, with only minimal formation of oxidative dimers. The reaction proceeds through the electrochemical generation of bromine, which reacts with indole and undergoes hydrolysis to yield the desired 2-oxindole. This procedure offers an attractive alternative to existing methods for accessing 2-oxindoles by oxidation of indoles.