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.