Catalytic C–F bond activation of geminal difluorocyclopropanes by nickel(<scp>i</scp>) complexes via a radical mechanism

Wenz, Jan; Rettenmeier, Christoph; Wadepohl, Hubert; Gade, Lutz H.

doi:10.1039/c5cc08950f

Cited by 79 publications

(45 citation statements)

References 48 publications

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“…51 These compounds catalyse hydrodehalogenation reactions, such as the dehalogenation of geminal dihalogenides, 51 and defluorination of geminal difluorocyclopropanes to fluoroalkenes. 52 Such reactions are regarded as a promising route to partially halogenated compounds from readily available perhalogenated species. 53 Both reactions are stereoselective, with moderate ee (enantiomeric excess) values for the monohalides of 20-74%, 51 and high Z-selectivity in the formation of alkenes from cyclopropanes.…”

Section: Scheme 3 Synthesis Of Ni Nhc Complexes For Kumada and Suzukimentioning

confidence: 99%

“…53 Both reactions are stereoselective, with moderate ee (enantiomeric excess) values for the monohalides of 20-74%, 51 and high Z-selectivity in the formation of alkenes from cyclopropanes. 52 Reactions with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) resulted in catalyst inhibition, suggesting that the mechanism is radical in nature. 51,52 This was further supported by reactions with radical clock reagents.…”

Section: Scheme 3 Synthesis Of Ni Nhc Complexes For Kumada and Suzukimentioning

confidence: 99%

“…52 Reactions with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) resulted in catalyst inhibition, suggesting that the mechanism is radical in nature. 51,52 This was further supported by reactions with radical clock reagents. 51 The proposed catalytic cycle for the dehalogenation of geminal dihalogenides is shown in Scheme 7b.…”

Section: Scheme 3 Synthesis Of Ni Nhc Complexes For Kumada and Suzukimentioning

confidence: 99%

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Low-coordinate first-row transition metal complexes in catalysis and small molecule activation

Taylor

Kays

2019

Dalton Trans.

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Section: Scheme 3 Synthesis Of Ni Nhc Complexes For Kumada and Suzukimentioning

confidence: 99%

Section: Scheme 3 Synthesis Of Ni Nhc Complexes For Kumada and Suzukimentioning

confidence: 99%

Section: Scheme 3 Synthesis Of Ni Nhc Complexes For Kumada and Suzukimentioning

confidence: 99%

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Low-coordinate first-row transition metal complexes in catalysis and small molecule activation

Taylor

Kays

2019

Dalton Trans.

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“…Diverse applications of fluorinated cyclopropanes promoted the development of general methods for their synthesis . Recently, we performed the difluorocyclopropanation of cyclic N ‐Boc protected enamides (activated alkenes) with CF 2 ClCO 2 Na or Dolbier reagent (FSO 2 CF 2 CO 2 TMS).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery

Bychek

Levterov

Sadkova

et al. 2018

Chemistry A European J

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“…It is not our aim Phenofluor 15 31 , PyFluor 16 32 and nickel-fluorido complexes 17a and 17b 33 together with (diethylamino)difluorosulfonium tetrafluoroborate 18 (XtalFluor-E). 34 .…”

Section: Figure 1 Structures Of Atorvastatin Fluoxetin and Ciproflomentioning

confidence: 99%

Fluorination methods in drug discovery

2016

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Fluorination reactions of medicinal and biologically-active compounds will be discussed. Late stage fluorination strategies of medicinal targets have recently attracted considerable attention on account of the influence that the fluorine atom can impart to targets of medicinal importance, such as a modulation of lipophilicity, electronegativity, basicity and bioavailability, this latter as a consequence of membrane permeability. Therefore, the recourse to late-stage fluorine substitution on compounds with already known and relevant biological activity can provide the pharmaceutical industry with new leads with improved medicinal properties. The fluorination strategies will take into account different fluorinating reagents, nucleophilic, electrophilic and of radical nature. Diverse families of organic compounds such as (hetero)aromatic rings, and aliphatic substrates (sp 3 , sp 2 , and sp carbon atoms) will be studied in late-stage fluorination reaction strategies. The omniphobicity/lipophilicity and electrostatic interactions can be considered among the most prominent effects. Thus, introducing fluorine into an organic compound can significantly alter its biological properties.One other subtle but important effect of introducing fluorine into the backbone of a medicinal target is the inflection of acidity and basicity of the parent compound 4 , which can change, inter alia, the binding affinity, and bioavailability. Highly basic groups can have a detrimental effect on the bioavailability of a drug. Thus introducing a fluorine atom next to a basic group can reduce its basicity, enhancing its membrane permeability, and increasing bioavailability. Although the replacement of hydrogen for fluorine does not have a profound steric influence, electrostatic interactions with other groups can change conformations significantly. The replacement of hydrogen for fluorine on aromatic rings is a well-known strategy to decelerate oxidative metabolic processes by Cytochrome P450 monooxygenases. In this respect, the electron-withdrawing properties of fluorine on aromatic rings, which can slow down hydrolytic metabolism, alter reaction rates and stability of intermediates. Fluorine substitution on aromatic rings is also known to increase binding affinity, as a result of enhancing electrostatic interactions.However, it is difficult to predict the influence of fluorine substitution on the overall profile in a given situation.As numerous reports attest 1 , the number of marketed drugs that contain a fluorine atom has increased rapidly. As of 2009, the FDA-had approved >140 fluorine-containing drugs. This review article is intended to present new synthetic methodologies 9 for accomplishing fluorination reactions on molecules (drugs/prodrugs) with pharmacological activity. It is not our aim (Figure 3). would be beneficial to the syntheses. 3a.-Conversion of C Ar -H into C Ar -F BondsXu and co-workers 38 have developed an ortho C-H bond fluorination of 2-phenoxyl pyridine derivatives through a palladium-catalyzed reaction v...

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Catalytic C–F bond activation of geminal difluorocyclopropanes by nickel(i) complexes via a radical mechanism

Cited by 79 publications

References 48 publications

Low-coordinate first-row transition metal complexes in catalysis and small molecule activation

Low-coordinate first-row transition metal complexes in catalysis and small molecule activation

Synthesis of Functionalized Difluorocyclopropanes: Unique Building Blocks for Drug Discovery

Fluorination methods in drug discovery

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