Palladium-Catalyzed Aryl Amination–Heck Cyclization Cascade: A One-Flask Approach to 3-Substituted Indoles (original) (raw)
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Multicomponent Assembly of Highly Substituted Indoles by Dual Palladium-Catalyzed Coupling Reactions
Angewandte Chemie International Edition, 2012
The development of new methods for the synthesis of heterocycles [1] continues to be an important area of chemical research, and new organometallic catalytic methods [2] are providing synthetic routes to important targets previously unavailable to the synthetic chemist. As indoles are ubiquitous in pharmaceuticals and in natural products, [3] dozens of methods for their construction have been developed. [4] The search for straightforward, diversity-oriented routes to indoles is of importance to both synthetic and biological researchers. [5] 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. [6] There are also reports of multicomponent reactions to form indoles. [7] We report herein a general palladium-catalyzed multicomponent assemblies for indole synthesis that incorporates both a Buchwald-Hartwig [8] reaction and an arene-alkene coupling [9] 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. [10] The overall one-pot three-step multicomponent assembly reported herein is illustrated in Scheme 1. Reaction optimization established that the use of the dppf ligand (1,1'-bis(diphenylphosphanyl)ferrocene; Scheme 2) and Cs 2 CO 3 as base (Table 1, entry 4) gave the best yields. When Xphos, tBuXphos, and Xantphos (entries 1, 2, and 3, [**] We thank the National Institute of Health (GM089153), the National Science Foundation (CHE-0910870 and CHE-030089 with the Pittsburgh Supercomputer Center) for their generous financial support. We also thank Prof. Annaliese Franz (UC Davis) and Prof. Tomislav Rovis (Colorado State) for helpful discussions. Supporting information (including experimental, spectral and computational data) for this article is available on the WWW under
Palladium-catalyzed amination and cyclization to heteroannellated indoles and carbazoles
Tetrahedron, 2003
New ortho-bromodiarylamines in the benzo[b]thiophene series were prepared by palladium-catalyzed amination, either in the benzene or in the thiophene ring. These were submitted to palladium-catalyzed cyclization, under different required conditions, to give several differently substituted thieno[3,2-c] or [2,3-b]carbazoles and indolo[3,2-b]benzo[b]thiophenes. This constitutes a novel synthetic route to both tetracyclic systems.
Angewandte Chemie International Edition, 2009
Dedicated to Professor Gerd Meyer on the occasion of his 60th birthday Palladium-catalyzed transformations are of immense importance in modern organic synthesis, especially for C À C bond formation. Prominent examples are, among many others, the Heck reaction [2] and the Stille cross-coupling, [3] which both enjoy frequent application in the synthesis of complex organic molecules. In the course of our research aimed at the synthesis of the antibiotic pestalone (1), we recently attempted to prepare compound 3 from the iodobromobenzaldehyde 2 by palladium-catalyzed Stille cross-coupling using allyltributylstannane (Scheme 1). However, the NMR data of the sole product did not correspond to those expected for 3. Instead, the isomeric indanol rac-4 had formed as was unambiguously confirmed by X-ray crystallography ).