Nickel-Catalyzed Cross-Electrophile Coupling of the Difluoromethyl Group for Fluorinated Cyclopropane Synthesis

Lucas, Erika L.; McGinnis, Tristan M.; Castro, Anthony J.; Jarvo, Elizabeth R.

doi:10.1055/s-0040-1706013

Cited by 9 publications

(2 citation statements)

References 22 publications

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“…12 Recently, Jorvo's lab took advantage of this method to synthesize the methoxydifluoromethylation compounds as starting material for the preparation of the interesting fluorinated cyclopropane products through Ni-catalyzed cross-electrophile coupling (Scheme 7). 13 As indole motifs are very common in bioactive molecules and natural products, the difluoromethylation of indole is an attractive transformation. We found that under Ir(ppy) 3 catalysis and using KI as the additive, the corresponding products 9 were obtained in 44−91% yields (Scheme 8).…”

Section: From Difluorocarbene Precursor To Radical Difluoromethyl Rea...mentioning

confidence: 99%

Photoredox Catalyzed Radical Fluoroalkylation with Non-Classical Fluorinated Reagents

Ouyang,

Qing

2024

J. Org. Chem.

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The emergence of photocatalysis has greatly advanced radical fluoroalkylation reactions. Central to this advancement is the introduction and refinement of radical reagents, which play a pivotal role in driving these reactions forward. Intriguingly, some of these reagents, previously not recognized for their radical properties, have emerged as key players in this area. In this Perspective, we provide an overview of four representative reagents pioneered by our laboratory, which have subsequently garnered extensive application in broader research contexts, including difluorocarbene precursors bromodifluoromethylphosphonium bromide, electrophilic sulfonylation reagent triflic anhydride, and nucleophilic trifluoromethylation reagent methyl fluorosulfonyldifluoroacetate (Chen's reagent). The integration of phosphonium reagents, triflic anhydride, and methyl fluorosulfonyldifluoroacetate into photocatalysis has enabled some unexpected reactivities and now notably expanded the capabilities in radical difluoromethylation, trifluoromethylation, and difluoroalkylation. Our discussion highlights how these atypical reagents have enriched the toolkit available for radical fluoroalkylations, offering insights that could inspire future research and application in this area.

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Section: From Difluorocarbene Precursor To Radical Difluoromethyl Rea...mentioning

confidence: 99%

Photoredox Catalyzed Radical Fluoroalkylation with Non-Classical Fluorinated Reagents

Ouyang,

Qing

2024

J. Org. Chem.

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“…For example, trisubstituted alkenyl fluorides serve as peptide bond mimics . One strategy for the synthesis of complex fluorinated moieties involves cross-coupling (XC) or cross-electrophile coupling (XEC) reactions of perfluorinated starting materials where one C–F bond is cleaved and others remain . For example, trifluoromethyl alkenes undergo XEC reactions, providing access to highly substituted difluorinated alkenes (Scheme a). − These reactions typically employ a radical precursor and proceed via radical addition to the alkene followed by radical-polar crossover and β-fluoride elimination.…”

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confidence: 99%

Stereospecific Nickel-Catalyzed Cross-Electrophile Coupling Reaction of Alkyl Mesylates and Allylic Difluorides to Access Enantioenriched Vinyl Fluoride-Substituted Cyclopropanes

et al. 2023

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Cross-electrophile coupling reactions involving direct C−O bond activation of unactivated alkyl sulfonates or C−F bond activation of allylic gem-difluorides remain challenging. Herein, we report a nickelcatalyzed cross-electrophile coupling reaction between alkyl mesylates and allylic gem-difluorides to synthesize enantioenriched vinyl fluoridesubstituted cyclopropane products. These complex products are interesting building blocks with applications in medicinal chemistry. Density functional theory (DFT) calculations demonstrate that there are two competing pathways for this reaction, both of which initiate by coordination of the electron-deficient olefin to the low-valent nickel catalyst. Subsequently, the reaction can proceed by oxidative addition of the C−F bond of the allylic gem-difluoride moiety or by directed polar oxidative addition of the alkyl mesylate C−O bond.

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Synthesis of Fluoromethyl‐Substituted Cyclopropanes by Electrophilic Cyclization of Homoallylic Boronate Intermediates

Oyama

Ito

2023

Adv Synth Catal

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The electrophilic cyclization via the boronate complex between various homoallylic boronates and Selectfluor® is reported. This reaction provides a fluoromethylated cyclopropane ring that was difficult to synthesize by previous methods. The use of phenyl lithium, which activates the homoallylic boronate, is important for the reaction. The intermediate boronate species in this reaction was observed through <sup>11</sup>B NMR experiments. We also demonstrate the synthesis of a building block including fluoromethyl‐substituted cyclopropane for a bioactive compound.

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Nickel-Catalyzed Cross-Electrophile Coupling of the Difluoromethyl Group for Fluorinated Cyclopropane Synthesis

Cited by 9 publications

References 22 publications

Photoredox Catalyzed Radical Fluoroalkylation with Non-Classical Fluorinated Reagents

Photoredox Catalyzed Radical Fluoroalkylation with Non-Classical Fluorinated Reagents

Stereospecific Nickel-Catalyzed Cross-Electrophile Coupling Reaction of Alkyl Mesylates and Allylic Difluorides to Access Enantioenriched Vinyl Fluoride-Substituted Cyclopropanes

Synthesis of Fluoromethyl‐Substituted Cyclopropanes by Electrophilic Cyclization of Homoallylic Boronate Intermediates

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