A Change in C–H Activation Mechanism: Experimental and Computational Investigations of Rh-Catalyzed Disubstituted Benzene Functionalization

We report the ethenylation of 1,3- and 1,2-disubstituted benzenes using [(η²-C₂H₄)₂Rh-(μ-OAc)]₂ as a catalyst precursor and Cu-(OPiv)₂ as the oxidant. The regioselectivity of alkenylation for 1,3-disubstituted benzenes produces 3,5-disubstituted styrene products, while the alkenylation of 1,2-disubstituted benzenes produces 3,4-disubstituted styrene products. The rate of alkenylation is influenced by steric and electronic factors based on the substituents of the benzene unit. In all cases, 1,2-disubstituted benzenes react faster than 1,3-disubstituted benzenes, with a rate difference that is from 2 times up to >70 times more rapid for 1,2-disubstituted substrates. This is likely due to the difference in the number of accessible C-H bonds based on the steric protection of C-H bonds adjacent to functionality. Furthermore, the rate of alkenylation is influenced by the arene substituent electronics. The rates of alkenylation for 1,2-disubstituted benzenes follow the trend OMe > Me > CF₃ > Cl, while for 1,3-disubstituted benzenes the trend is CF₃ > Cl > Me > OMe. Using quantum mechanics DFT calculations, we found that the C-H activation step can occur by two different mechanisms. The electronic properties of substituents on the arene ring change the preferred C-H bond-breaking mechanism for 1,2-disubstituted and 1,3-disubstituted benzenes.