Multicomponent Assembly of Highly Substituted Indoles by Dual Palladium-Catalyzed Coupling Reactions

摘要

The development of new methods for the synthesis of heterocycles continues to be an important area of chemical research, and new organometallic catalytic methods are providing synthetic routes to important targets previously unavailable to the synthetic chemist. As indoles are ubiquitous in pharmaceuticals and in natural products, dozens of methods for their construction have been developed. The search for straightforward, diversity-oriented routes to indoles is of importance to both synthetic and biological researchers. Some of these synthetic strategies have involved the use of palladium catalysis and there are reports of indole syntheses using Heck and Buchwald-Hartwig assemblies. There are also reports of multicomponent reactions to form indoles. We report herein a general palladium-catalyzed multicomponent assemblies for indole synthesis that incorporates both a Buchwald-Hartwig reaction and an arene-alkene coupling reaction and requires a single catalyst/ligand system. This method involves three components and allows for easy diversification from readily available starting materials. Multicomponent reactions are advantageous in that they provide expedient methods for the construction of complex structures, minimize synthetic steps, and use relatively simple starting materials. The overall one-pot three-step multicomponent assembly reported herein is illustrated in Scheme 1.