Efficient and versatile synthesis of indoles from enamines and imines by cross-dehydrogenative coupling.

The indole unit is one of the most abundant and relevant heterocycles in natural products and pharmaceuticals. The synthesis of indoles has been a topic of research for over 100 years, and a variety of well-established classical methods are now available. The venerable Fischer indole synthesis, discovered in 1883, remains one of the most powerful and versatile routes to the indole heterocycle, although this method suffers from several drawbacks. A variety of synthetic modifications have been introduced to increase the practicality and lessen the environmental impact of the Fischer cyclization such as using mild acids, reusable catalysts, and ionic liquids. However, it is important to note that hydrazines are carcinogenic and that certain hydrazines are difficult to prepare, are unstable, or display only moderate functional-group tolerance under acidic conditions (Scheme 1a).