Radical Chlorodifluoromethylation: Providing a Motif for (Hetero)arene Diversification

McAtee, Rory C.; Beatty, Joel W.; McAtee, Christopher C.; Stephenson, Corey R. J.

doi:10.1021/acs.orglett.8b01249

Cited by 66 publications

(45 citation statements)

References 65 publications

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“…Through a collaboration with Eli Lilly this scale was increased to 1.2 kg in a continuous flow system (50 % yield) . The methodology was later on expanded to radical perfluoroalkylation and chloro‐difluoromethylation of (hetero)arenes …”

Section: C–c Bond: Sp2‐sp3 Disconnectionmentioning

confidence: 99%

A Retrosynthetic Approach for Photocatalysis

et al. 2020

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Visible‐light‐mediated chemical reactions have become very popular within the last 15 years. Many excellent reviews have summarized reaction principles and recent results in photochemistry and photocatalysis. However, despite their popularity photochemistry and photoredox catalysis are not regular parts of the bachelor and master curriculum of chemistry education. As a consequence, most chemists will use in synthesis planning classic retrosynthetic disconnections and only rarely consider photocatalytic steps. The aim of this article is to be a useful tool for synthetic chemists, that are interested in the synthetic aspects of photocatalysis and looking for a specific retrosynthetic disconnection. Not only are informative schemes provided but also are the availability of the catalysts and reagents as well as the functional group tolerance of the respective method briefly discussed.

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Section: C–c Bond: Sp2‐sp3 Disconnectionmentioning

confidence: 99%

A Retrosynthetic Approach for Photocatalysis

et al. 2020

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“…McAtee, Stephenson, and colleagues [35] have informed the chloro-difluoromethylation of (hetero)arenes. While the difluoromethyl radical CF 2 H exhibits nucleophilic behavior, the chlorodifluoromethyl CF 2 Cl radical may be characterized as an electrophilic radical.…”

Section: (Het) -H Difluoromethylation Of (Hetero)aromatic Compoundsmentioning

confidence: 99%

“…Therefore, the CF 2 Cl radical can be considered as an attractive surrogate to the difluoromethyl radical and a means to efficiently prepare electron-rich difluoromethylated (hetero)arenes and other high-value, fluorinated heterocycles. The authors in [35] employed commercially available chlorodifluoroacetic anhydride as a source of CF 2 Cl radicals and found that with benzene as the substrate, a combination of pyridine-N-oxide, chlorodifluoroacetic anhydride, photocatalyst Ru(bpy) 2 Scheme 1. Selected examples of chlorodifluoromethylation of (hetero)arenes.…”

Section: (Het) -H Difluoromethylation Of (Hetero)aromatic Compoundsmentioning

confidence: 99%

Photocatalytic Difluoromethylation Reactions of Aromatic Compounds and Aliphatic Multiple C–C Bonds

Barata‐Vallejo

Postigo

2019

Molecules

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Among the realm of visible light photocatalytic transformations, late-stage difluoromethylation reactions (introduction of difluoromethyl groups in the last stages of synthetic protocols) have played relevant roles as the CF2X group substitutions exert positive impacts on the physical properties of organic compounds including solubility, metabolic stability, and lipophilicity, which are tenets of considerable importance in pharmaceutical, agrochemical, and materials science. Visible-light-photocatalyzed difluoromethylation reactions are shown to be accomplished on (hetero)aromatic and carbon–carbon unsaturated aliphatic substrates under mild and environmentally benign conditions.

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“…Stephenson's group achieved the radical chloro‐difluoromethylation of arenes and heteroarenes ( 190 ) by in situ formation of a redox‐active complex resulting from the combination of heterocyclic N ‐oxides (pyridine N ‐oxide and 4‐phenylpyridine N ‐oxide) with the commercially available chlorodifluoroacetic anhydride [(ClCF 2 CO) 2 O, CAS number: 2834‐23‐3], in the presence of [Ru(bpy) 3 ]Cl 2. Electron‐rich heteroarenes and other pharmaceutically valuable agents with diverse functional groups were competent substrates for the desired organic transformation under both batch and flow conditions ( 191 , Scheme : 19 examples, 25–84% yields). Interestingly, the chlorodifluoromethyl group‐containing compounds ( 191 ) can be used as synthetic percursors to access electron‐rich difluoromethylated arenes and heteroarenes.…”

Section: General Introductionmentioning

confidence: 99%

Progress in Difluoroalkylation of Organic Substrates by Visible Light Photoredox Catalysis

2019

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Thes electivei ncorporation of fluorinated motifs, in particularC F 2 FG (FG = af unctional group) and CF 2 Hg roups,i ntoo rganic compounds has attrracted increasing attention since organofluorine molecules are of the utmost importance in the areas of nuclear imaging,pharmaceutical, agrochemical, and material sciences.Avariety of synthetic approachesh as been employed in late-stage difluoroalkylationr eactions.V isible light photoredox catalysis for the production of CF 2 FG and CF 2 Hr adicalsh as providedamore sustainable alternative to other conventional radical-triggered reactions from the viewpoint of safety,c ost, availability,a nd "green"c hemistry.Awide range of difluoroalkylating reagents has been successfully implemented in these organic transformationsi nt he presence of transitionm etal complexes or organic photocatalysts.I nmost cases, upon excitation via visible light irradiation with fluorescent light bulbs or blue light-emitting diode (LED) lamps,t hese photocatalysts can act as both reductivea nd oxidative quenchers,t hus enabling the applicationo fe lectron-donoro re lectron-acceptor difluoroalkylating reagents for the generation of CF 2 FG andC F 2 Hr adicals.S ubsequent radical addition to substrates and additional organic transformations affordt he corresponding difluoroalkylatedd erivatives.T he presentr eview describes the distinct strategies for the transitionm etal-and organic-pho-tocatalyzed difluoroalkylation of ab road range of organic substrates by visible light irradiationr eported in the literature since 2014.

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Radical Chlorodifluoromethylation: Providing a Motif for (Hetero)arene Diversification

Cited by 66 publications

References 65 publications

A Retrosynthetic Approach for Photocatalysis

A Retrosynthetic Approach for Photocatalysis

Photocatalytic Difluoromethylation Reactions of Aromatic Compounds and Aliphatic Multiple C–C Bonds

Progress in Difluoroalkylation of Organic Substrates by Visible Light Photoredox Catalysis

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