Conspectus
In recent years, the development of light-driven
reactions has
contributed numerous advances in synthetic organic chemistry. A particularly
active research area combines photoredox catalysis with nickel catalysis
to accomplish otherwise inaccessible cross-coupling reactions. In
these reactions, the photoredox catalyst absorbs light to generate
an electronically excited charge-transfer state that can engage in
electron or energy transfer with a substrate and the nickel catalyst.
Our group questioned whether photoinduced activation of the nickel
catalyst itself could also contribute new approaches to cross-coupling.
Over the past 5 years, we have sought to advance this hypothesis for
the development of a suite of mild and site-selective C(sp3)–H cross-coupling reactions with chloride-containing coupling
partners via photoelimination of a Ni–Cl bond.
On the
basis of a report from the Nocera laboratory, we reasoned
that photolysis of a Ni(III) aryl chloride species, generated by single-electron
oxidation of a typical Ni(II) intermediate in cross-coupling, might
allow for the catalytic generation of chlorine atoms. Combining this
with the ability of Ni(II) to accept alkyl radicals, we hypothesized
that photocatalytically generated chlorine atoms could mediate hydrogen
atom transfer (HAT) with C(sp3)–H bonds to generate
a substrate-derived alkyl radical that is captured by the Ni center
in cross-coupling. A photoredox catalyst was envisioned to promote
the necessary single-electron oxidation and reduction of the Ni catalyst
to facilitate an overall redox-neutral process. Overall, this strategy
would offer a visible-light-driven mechanism for chlorine radical
formation enabled by the sequential capture of two photons.
As an initial demonstration, we developed a Ni/photoredox-catalyzed
α-oxy C(sp3)–H arylation of cyclic and acyclic
ethers. This method was extended to a mild formylation of abundant
and complex aryl chlorides through selective 2-functionalization of
1,3-dioxolane. Seeking to develop a suite of reactions that introduce
carbon at all different oxidation states, we explored C(sp3)–H cross-coupling with trimethyl orthoformate, a common laboratory
solvent. We found that trimethyl orthoformate serves as a source of
methyl radical for a methylation reaction via β-scission from
a tertiary radical generated upon chlorine-mediated HAT. Since chlorine
radical is capable of abstracting unactivated C(sp3)–H
bonds, our efforts have also been directed at cross-coupling with
a range of feedstock chemicals, such as alkanes and toluenes, along
with late-stage intermediates, using chloroformates as coupling partners.
Overall, this platform enables access to valuable synthetic transformations
with (hetero)aryl chlorides, which despite being the most ubiquitous
and inexpensive aryl halide coupling partners, are rarely reactive
in Ni/photoredox catalysis.
Little is known about the photophysics
and photochemistry of organometallic
Ni complexes relevant to cross-coupling. We have conducted mechanistic
investig...