title: Combined experimental and computational investigations of rhodium- and ruthenium-catalyzed C-H functionalization of pyrazoles with alkynes.
abstract: Detailed experimental and computational studies are reported on the mechanism of the coupling of alkynes with 3-arylpyrazoles at [Rh(MeCN)3Cp*][PF6]2 and [RuCl2(p-cymene)]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 κ(2)-κ(1) 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(H)/k(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 κ(2)-κ(1) displacement of acetate and so is still consistent with the lack of a significant experimental isotope effect (k(H)/k(D) = 1.1 ± 0.2).
authors.affiliation: Institute of Chemical Sciences, Heriot-Watt University , Edinburgh EH14 4AS, U.K.
authors.forename: Andrés G
authors.initials: AG
authors.lastname: Algarra
authors.forename: Warren B
authors.initials: WB
authors.lastname: Cross
authors.forename: David L
authors.initials: DL
authors.lastname: Davies
authors.forename: Qudsia
authors.initials: Q
authors.lastname: Khamker
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Macgregor
authors.forename: Claire L
authors.initials: CL
authors.lastname: McMullin
authors.forename: Kuldip
authors.initials: K
authors.lastname: Singh