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Gold-catalyzed activation of alkynes towards functional molecules remains an interesting endeavor with industrial potential, yet stable, efficient catalysts are needed. Here, we report a shelf-stable tricoordinate Au(I) catalyst for the cyclization of anilino-alkyne derivatives to form C2-substituted indoles and other benzo-fused Nheterocycles. We also report the use of this Au(I) catalyst for intermolecular hydroamination of ethynylbenzene and diphenylacetylene with various aniline derivatives, forming imines. The distorted geometry of Au(I) complexes facilitates alkyne activation and demonstrates functional group tolerance of the catalyst under mild conditions. We expand the scope of previously synthesized benzo-fused N-heterocycles and demonstrate potential for tricoordinate complexes in catalytic systems.
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Thioarylation of Alkynes to Generate Dihydrothiopheniums through Gold(I)/(III)-Catalyzed Cyclization–Cross-Coupling
A thioarylation method is developed for the synthesis of 2,3-dihydrothiopheniums through an electrophilic-cyclization–cross-coupling mechanism, harnessing the gold(I)/(III) cycle of the recently developed MeDalPhosAuCl catalyst. Single-crystal X-ray crystal structural analysis of the dihydrothiophenium products characterized the anti-addition of the sulfur and Csp2 group to the alkyne and a preference for 5-endo dig cyclization. The dihydrothiophenium products are demonstrated as synthetic building blocks for stereodefined acyclic tetrasubstituted alkenes upon ring-opening reaction with amines. Intramolecular competition experiments show the favorability of Csp3 tether cyclizations over Csp2 tethers, preferentially generating dihydrothiopheniums over thiopheniums. Intermolecular competition experiments of alkyne aryl groups and an intermolecular aryl iodide competition suggest a rate-determining reductive elimination step in the gold(I)/gold(III) catalytic cycle. This rate-determining step is further supported by HRMS analysis of reaction intermediates that identify the catalyst resting state under turnover conditions. Catalyst poisoning experiments provide evidence of substrate inhibition, further consistent with these conclusions.
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- Award ID(s):
- 2102493
- PAR ID:
- 10613602
- Publisher / Repository:
- Journal of Organic Chemistry
- Date Published:
- Journal Name:
- The Journal of Organic Chemistry
- Volume:
- 89
- Issue:
- 19
- ISSN:
- 0022-3263
- Page Range / eLocation ID:
- 14384 to 14398
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.joc.4c01777
