posted on 2024-03-13, 11:38authored byVictor
O. Nyagilo, Sharath Chandra Mallojjala, Jennifer S. Hirschi
A combination
of inter- and intramolecular 13C kinetic
isotope effects and density functional theory analysis is used to
evaluate the key mechanistic events of sequentially operating catalytic
cycles in the dual photoredox-cobalt-catalyzed elimination of alkyl
bromides. The results point to a mechanism proceeding via irreversible
halogen-atom transfer (XAT) from the alkyl halide, resulting in an
alkyl radical, which undergoes hydrogen-atom transfer (HAT) to a Co(II)
intermediate to deliver the product olefin. Alternative pathways involving
nucleophilic substitution by a Co(I) species and by β-hydride
elimination are discounted based on the poor agreement of experimental
and predicted 13C KIEs. This mechanistic understanding
is used to evaluate the origins of regioselectivity in the elimination
step for an unsymmetrical alkyl halide catalyzed by electronically
and sterically distinct cobaloxime catalysts. This study represents
the experimental validation of the key features of the transition
state structure of XAT by α-aminoalkyl radicals, an important
class of atom transfer reactions that generate carbon-centered radicals
from alkyl and aryl halides. Furthermore, it illustrates the power
of 13C KIEs in probing complex mechanisms in metallaphotoredox
catalysis.