posted on 2023-01-05, 19:41authored byFanshu Cao, Ping Wu, Yu Zhou, Ni Zhang, Zuqian Xue, Lei Shi, Guangli Zhou, Gen Luo
Benzylic C(sp3)–H alkylation of tertiary
anilines
with alkenes by an anilido-oxazoline-ligated scandium alkyl catalyst
was recently reported with C–H site selectivity and alkene-dependent
regioselectivity. Revealing the mechanism and origin of selectivity
is undoubtedly of great importance for understanding experimental
observations and developing new reactions. Herein, density functional
theory (DFT) calculations have been carried out on the model reaction
of Sc-catalyzed benzylic C(sp3)–H alkylation of N,N-dimethyl-o-toluidine
with allylbenzene. The reaction generally undergoes the generation
of active species, alkene insertion, and protonation steps. The difference
of the distortion energy of the aniline moiety in transition states,
which is related to the ring size of the forming metallacycles, accounts
for the site selectivity of C–H activation. Benzylic C(sp3)–H activation possessing less strained five-membered
metallacycle compared to the ortho-C(sp2)–H and α-methyl C(sp3)–H activation
results in benzylic C(sp3)–H alkylation observed
experimentally. Both steric and electronic factors are responsible
for the 1,2-insertion regioselectivity for alkyl-substituted alkenes,
while electronic factors control the 2,1-insertion manner for vinylsilanes.
The analysis of original alkene substrates further strengthens the
understanding of the alkene-dependent regioselectivity. These results
help us to obtain the mechanistic understanding and are expected to
be conducive to the development of new C–H functionalization
reactions.