Combined Experimental and Computational Investigations of Rhodium-Catalysed CH Functionalisation of Pyrazoles with Alkenes

Detailed experimental and computational studies have been carried out on the oxidative coupling of the alkenes C2H3Y (Y=CO2Me (a), Ph (b), C(O)Me (c)) with 3‐aryl‐5‐R‐pyrazoles (R=Me (1 a), Ph (1 b), CF3 (1 c)) using a [Rh(MeCN)3Cp*][PF6]2/Cu(OAc)2⋅H2O catalyst system. In the reaction of methyl acrylate with 1 a, up to five products (2 aa–6 aa) were formed, including the trans monovinyl product, either complexed within a novel CuI dimer (2 aa) or as the free species (3 aa), and a divinyl species (6 aa); both 3 aa and 6 aa underwent cyclisation by an aza‐Michael reaction to give fused heterocycles 4 aa and 5 aa, respectively. With styrene, only trans mono‐ and divinylation products were observed, whereas with methyl vinyl ketone, a stronger Michael acceptor, only cyclised oxidative coupling products were formed. Density functional theory calculations were performed to characterise the different migratory insertion and β‐H transfer steps implicated in the reactions of 1 a with methyl acrylate and styrene. The calculations showed a clear kinetic preference for 2,1‐insertion and the formation of trans vinyl products, consistent with the experimental results. Selective vinylation: The rhodium‐catalysed oxidative coupling of alkenes and 3‐aryl‐5‐R‐pyrazoles gives vinylated products, some of which can cyclise through intramolecular Michael reactions (see scheme). DFT calculations show a clear preference for 2,1‐insertion with β‐H elimination, calculated to favour the trans vinyl products in all cases, as found experimentally.