Combined Experimental and Computational Investigations of Rhodium‐Catalysed CH Functionalisation of Pyrazoles with Alkenes

Abstract

Detailed experimental and computational studies have been carried out on the oxidative coupling of the alkenes C2 H3 Y (Y=CO2 Me (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)3 Cp*][PF6 ]2 /Cu(OAc)2 ⋅H2 O 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 Cu(I) 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.