Synthetic and Mechanistic Implications of Chlorine Photoelimination in Nickel/Photoredox C(sp³)–H Cross-Coupling

Journal Article · Fri Jan 29 00:00:00 EST 2021 · Accounts of Chemical Research

DOI:https://doi.org/10.1021/acs.accounts.0c00694· OSTI ID:1776559

Kariofillis, Stavros K. ^[1]; Doyle, Abigail G. ^[2]

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1. Princeton Univ., NJ (United States); Princeton University
2. Princeton Univ., NJ (United States)

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 investigations, including computational, spectroscopic, emission quenching, and stoichiometric oxidation studies, of Ni(II) aryl halide complexes common to Ni/photoredox reactions. These studies indicate that chlorine radical generation from excited Ni(III) is operative in the described C(sp³)–H functionalization methods. More generally, the studies illustrate that the photochemistry of cross-coupling catalysts cannot be ignored in metallaphotoredox reactions. We anticipate that further mechanistic understanding should facilitate catalyst design and lead to the development of new synthetic methods.

• Research Organization: Princeton Univ., NJ (United States)
• Sponsoring Organization: National Science Foundation (NSF); USDOE Office of Science (SC); USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division
• Grant/Contract Number: SC0019370
• OSTI ID: 1776559
• Alternate ID(s): OSTI ID: 1784549
• Journal Information: Accounts of Chemical Research, Journal Name: Accounts of Chemical Research Journal Issue: 4 Vol. 54; ISSN 0001-4842
• Publisher: American Chemical Society
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Anions
Chlorine
Cross coupling reaction
Functionalization
Organic reactions