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Title: Combined experimental and computational investigations of rhodium- and ruthenium-catalyzed C−H functionalization of pyrazoles with alkynes
Authors: Algarra, Andrés G.
Cross, Warren B.
Davies, David L.
Khamker, Qudsia
Macgregor, Stuart A.
McMullin, Claire L.
Singh, Kuldip
First Published: 24-Feb-2014
Publisher: American Chemical Society
Citation: Journal of Organic Chemistry, 2014, 79 (5), pp. 1954-1970
Abstract: Detailed experimental and computational studies are reported on the mechanism of the coupling of alkynes with 3-arylpyrazoles at [Rh(MeCN)[subscript 3]Cp*][PF[subscript 6]][subscript 2] and [RuCl[subscript 2](p-cymene)][subscript 2] catalysts. Density functional theory (DFT) calculations indicate a mechanism involving sequential N−H and C−H bond activation, HOAc/alkyne exchange, migratory insertion, and C−N reductive coupling. For rhodium, C−H bond activation is a two-step process comprising κ²−κ¹ displacement of acetate to give an agostic intermediate which then undergoes C−H bond cleavage via proton transfer to acetate. For the reaction of 3-phenyl-5-methylpyrazole with 4-octyne k[subscript H]/k[subscript D] = 2.7 ± 0.5 indicating that C−H bond cleavage is rate limiting in this case. However, H/D exchange studies, both with and without added alkyne, suggest that the migratory insertion transition state is close in energy to that for C−H bond cleavage. In order to model this result correctly, the DFT calculations must employ the full experimental system and include a treatment of dispersion effects. A significantly higher overall barrier to catalysis is computed at {Ru(p-cymene)} for which the rate-limiting process remains C−H activation. However, this is now a one-step process corresponding to the κ²−κ¹ displacement of acetate and so is still consistent with the lack of a significant experimental isotope effect (k[subscript H]/k[subscript D] = 1.1 ± 0.2).
DOI Link: 10.1021/jo402592z
ISSN: 0022-3263
eISSN: 1520-6904
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014, American Chemical Society. Deposited with reference to the publisher’s archiving policy available on the SHERPA/RoMEO website.
Description: The file associated with this record is embargoed until 12 months after the date of publication. The final published version may be available through the links above.
Appears in Collections:Published Articles, Dept. of Chemistry

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