The manganese porphyrin-catalyzed C−H bond hydroxylation and amidation of equilenin acetate developed by Breslow and his co-worker have been investigated with density functional theory (DFT) calculations. The hydroxylation of C(sp 2 )−H bond of equilenin acetate leading to the 6-hydroxylated product is more favorable than the hydroxylation of C(sp 3 )−H bond of equilenin acetate, leading to the 11β-hydroxylation product. The computational results suggest that the C(sp 2 )−H bond hydroxylation of equilenin acetate undergoes an oxygenatom-transfer mechanism, which is more favorable than the C(sp 3 )−H bond hydroxylation undergoing the hydrogen-atomabstraction/oxygen-rebound (HAA/OR) mechanism by 1.6 kcal/ mol. That is why, the 6-hydroxylated product is the major product and the 11β-hydroxylated product is the minor product. In contrast, the 11β-amidated product is the only observed product in manganese porphyrin-catalyzed amidation reaction. The benzylic amidation undergoes a hydrogen-atom-abstraction/nitrogen-rebound (HAA/NR) mechanism, in which hydrogen atom abstraction is followed by nitrogen rebound, leading to the 11β-amidated product. The benzylic C(sp 3 )−H bond amidation at the C-11 position is more favorable than aromatic amidation at the C-6 position by 4.9 kcal/mol. Therefore, the DFT computational results are consistent with the experiments that manganese porphyrin-catalyzed C−H bond hydroxylation and amidation of equilenin acetate have different regioselectivities.
The mechanism of Pd(II)-catalyzed meta-C–H
bond olefination of arenes with a carboxyl directing group (DG)-containing
template has been investigated with density functional theory. The
reaction includes three major steps: C–H bond activation, alkene
insertion, and β-hydride elimination. The C–H activation
step, which proceeds via a concerted metalation–deprotonation
pathway, is found to be the rate- and regioselectivity-determining
step. We proposed a mono-N-protected amino acid (MPAA)/DG-assisted
C–H activation model, in which the carboxyl DG coordinates
with the Pd center and delivers it to the meta-position
of arene, and the bidentate dianionic MPAA acts as a base for deprotonation.
There is a hydrogen bonding interaction between the carboxyl DG and
the carboxylate group of MPAA. An alternative Pd(OAc)2-catalyzed
mechanism without involvement of MPAA is also operative. The template
is conformationally flexible, and multiple low-energy transition-state
conformations contribute to the regioselectivity.
We explored the mechanism and origins of chemoselectivity of manganese porphyrin-catalyzed aliphatic C–H isocyanation reaction with density functional theory (DFT) calculations. In this reaction, a diradical intermediate complex of a...
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