Synthesis of (difluoromethyl)naphthalenes using the ring construction strategy: C–C bond formation on the central carbon of 1,1-difluoroallenes <i>via</i> Pd-catalyzed insertion

Fuchibe, Kohei; Watanabe, Shumpei; Takao, Go; Ichikawa, Junji

doi:10.1039/c9ob00540d

Cited by 4 publications

(2 citation statements)

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“…Bond-forming reactions at the position b to the fluorine substituents were facilitated by a palladium catalyst involving p-allylpalladium(II) formation. 12 Difluoroallene 16 with a bromophenyl moiety was intramolecularly carbopalladated to form the p-allylpalladium(II) species with a sixmembered ring structure, which in turn underwent b-hydrogen elimination, followed by isomerization to yield difluoromethylated naphthalene 17 in 60% yield (Scheme 6). The difluoromethyl group is a bioisostere of a hydroxy group and is attracting attention in the field of pharmaceuticals and agrochemicals as a hydrogen donor for hydrogen bonding while simultaneously exhibiting hydrophobicity.…”

Section: Bond Forming Reactions On the B-carbonmentioning

confidence: 99%

Discussion Addendum for: Preparation of 1,1-Difluoroallenes by Difluorovinylidenation of Carbonyl Compounds

Fuchibe

2022

Org. Synth.

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Section: Bond Forming Reactions On the B-carbonmentioning

confidence: 99%

Discussion Addendum for: Preparation of 1,1-Difluoroallenes by Difluorovinylidenation of Carbonyl Compounds

Fuchibe

2022

Org. Synth.

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“…The synthesis of (difluoromethyl)naphthalenes was accomplished through an intramolecular insertion of 1,1-difluoroallenes at the central carbon (Scheme 82). [63] Treatment of obromophenyls bearing tethered 1,1-difluoroallenes (284) with a Pd 0 catalyst system generated an array of (difluoromethyl) naphthalenes (285) via regioselective CÀ C bond formation at the β-position relative to the fluorine substituents. Notably, this reaction generated products bearing two fluorine atoms and did not involve a defluorination event.…”

Section: Synthesis Of Difluoromethyl Derivativesmentioning

confidence: 99%

Recent Advances in Transition Metal‐Catalyzed Functionalization of gem‐Difluoroalkenes

Koley

Altman

2020

Israel Journal of Chemistry

122

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gem-Difluorinated alkenes are readily accessible building blocks that can undergo functionalization to provide a broad spectrum of fluorinated and non-fluorinated products. Herein, we review recent (since 2017) transition metalcatalyzed transformations of these specialized alkenes and summarize general reactivity patterns of these reactions. Many transition metal-catalyzed reactions undergo net CÀ F bond functionalization reactions to deliver monofluorinated products. These reactions typically proceed through β-fluoroalkylmetal intermediates that readily eliminate a βfluoride to deliver monofluoroalkene products. A second series of reactions exploit coinage metal fluorides to add F À to the gem-difluorinated alkene, and further functionalization delivers trifluoromethyl-containing products. In stark contrast, few transition metal-catalyzed reactions proceed in net "fluorine-retentive processes" to deliver difluoromethylenebased products. Reactions Proceeding via β-Fluoride Eliminationgem-Difluoroalkenes react with a variety of transition metalbased catalyst systems (e. g. Cu, Co, Mn, Pd, Ni, Ru, Rh) in net CÀ F functionalization reactions. These reactions typically proceed through a β-fluoroalkylmetal intermediate that readily undergoes β-fluoride elimination to form a new alkene based product (Scheme 1). At first, reaction of a substrate-ligated complex (1) to the gem-difluoroalkene 2, proceeds through a four-membered transition state 3 to generate the intermediate 4. This process involves the matching of the anionic ligand (Y) with the cationic α,α-difluorinated position of the alkene, which generates an intermediate metalalkyl bearnig two βfluoride atoms. Subsequent β-fluoride elimination generates [a] S.Scheme 3. Plausible mechanism for defluoroborylation of aliphatic gem-difluoroalkenes. Scheme 4. CÀ F Bond borylation of gem-difluoroalkenes. Scheme 5. Copper-catalyzed trans-selective monodefluoroborylation of various gem-difluoroalkenes. Scheme 6. CÀ F Bond borylation of gem-difluoroalkenes. Scheme 7. Copper-catalyzed tunable multi-borylation reactions of gem-difluoroalkenes. In parentheses the ratio of 22, 23 and 24 is reported. Scheme 8. Stereoselective defluorinative borylation and silylation of gem-difluoroalkenes. Scheme 9. a) Synthesis of fluorinated vinylsilanes from gem-difluoro/ polyfluoroalkenes. b) Cross-coupling reaction of 29 b and iodobenzene. Scheme 10. Nickel-catalyzed fluoroalkenylation of unactivated alkylbromides. rr = The regioisomeric ratio of the benzylic fluoroÀ alkenylation product to the other regioisomers. DMA = N,N-Dimethylacetamide. Scheme 14. Iron-catalyzed defluorinative cross-coupling of donor alkenes with gem-difluoroalkenes. Dibm = diisobutyrylmethane. Scheme 15. Nickel-catalyzed reductive aryl monofluoroalkenylation of alkenes. Scheme 16. Plausible mechanism for reductive aryl monofluoroalkenylation of gem-difluoroalkenes. Scheme 17. Nickel-catalyzed hydroalkenylation of alkynes through oxidative cyclization and β-fluoride elimination. Scheme 28. Ruthenium-catalyzed fluoroal...

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Preparation of 1,1‐Difluoroallenes by Difluorovinylidenation of Carbonyl Compounds

Fuchibe¹,

Abe²,

Oh³

et al. 2017

Organic Syntheses

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Synthesis of (difluoromethyl)naphthalenes using the ring construction strategy: C–C bond formation on the central carbon of 1,1-difluoroallenes via Pd-catalyzed insertion

Abstract: 1,1-Difluoroallenes underwent β-selective C–C bond formation (insertion) via π-allylpalladium(ii) to facilitate aromatic ring construction, leading to biologically promising (difluoromethyl)naphthalenes.

Cited by 4 publications

References 74 publications

Discussion Addendum for: Preparation of 1,1-Difluoroallenes by Difluorovinylidenation of Carbonyl Compounds

Discussion Addendum for: Preparation of 1,1-Difluoroallenes by Difluorovinylidenation of Carbonyl Compounds

Recent Advances in Transition Metal‐Catalyzed Functionalization of gem‐Difluoroalkenes

Preparation of 1,1‐Difluoroallenes by Difluorovinylidenation of Carbonyl Compounds

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