Monosubstituted 3,3‐Difluorocyclopropenes as Bench‐Stable Reagents: Scope and Limitations

Nosik, Pavel S.; Pashko, Mykola O.; Poturai, Andrii S.; Kvasha, Denys A.; Pashenko, Alexander; Роженко, А. Б.; Suikov, S. Yu.; Volochnyuk, Dmitriy M.; Yagupolskii, Yurii L.

doi:10.1002/ejoc.202100921

Cited by 6 publications

(5 citation statements)

References 56 publications

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“…Our investigations began by studying the strain-release Doyle–Kirmse reaction using tert -butyl diazoacetate ( 1a ) and ((3,3-difluorocycloprop-1-en-1-yl)methyl)(phenyl)sulfane ( 2a ), which is readily obtained by the reaction of phenyl propargyl sulfide with TMSCF 3 . 13 First, we evaluated metal catalysts used for both metallocarbene formation and Lewis acid activation. Pleasingly, in the presence of Rh 2 (OAc) 4 catalyst, the desired F2MCP 3a was obtained in 22% yield with excellent diastereoselectivity along with a large amount of C–H insertion product 4 (Table 1, entry 1).…”

Section: Resultsmentioning

confidence: 99%

A highly diastereoselective strain-release Doyle–Kirmse reaction: access to functionalized difluoro(methylene)cyclopropanes

Midya,

Hari

2023

Chem. Sci.

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Section: Resultsmentioning

confidence: 99%

A highly diastereoselective strain-release Doyle–Kirmse reaction: access to functionalized difluoro(methylene)cyclopropanes

Midya,

Hari

2023

Chem. Sci.

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“…Monosubstituted cyclopropenones 3a–3d were synthesized according to an effective, two-step sequence from corresponding acetylenes. The first step, difluorocyclopropenation of triple bond with TMSCF 3 as a source of difluorocarbene, has limitations such as the absence of certain functional groups ( e.g. , −O H , −CON H R, and amines) in the acetylene substrates.…”

Section: Resultsmentioning

confidence: 99%

Indolizin-1-ols with Charged Electron Acceptors: A Direct Way to 3H-Indolizinium-1-olates with Donor Functions

Nechaev

Cherkaev

2022

J. Org. Chem.

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The reaction of cyclopropenones with pyridines, having an attached integer-charged electron-withdrawing group (pyridinium, imidazolium, and phosphonium) was discovered to afford novel indolizin-1-ol derivatives in high yields with no chromatographic purification required. While being stable as solids, these indolizin-1-ols have a limited lifetime in solution. The study of reasons for such instability uncovered an aerobic oxidative pathway, eventually resulting in indolizine-1,7-dione dimers. The exploration of N-(1-hydroxyindolizin-7-yl)pyridinium salts’ chemistry led to a reaction discovery, affording a new type of rare pseudo-cross-conjugated mesomeric betaines (3H-indolizin-4-ium-1-olates with an electron-donating function at C7 position) inaccessible by other means. In this reaction, a sequential introduction of nucleophiles takes place: the first one (Nu1) is represented by simple anilines, whereas Nu2 extends to primary, secondary, aliphatic, aromatic amines, and phenols. For the obtained betaines having unsymmetrical aliphatic amino groups at C7 position an increased order of the C7−Nu2 bond resulting in existence of amide type E/Z-forms (∼1:1 at room temperature) was demonstrated. For aryl amino groups, with typically reduced nitrogen’s lone-pair donation, the barrier of rotation around the C7–Nu2 bond was lower, and for the C7-oxy betaines, no such E/Z-isomerism was revealed. Although primary amines (as Nu2) introduce a hydrogen atom in the conjugated betaine system, allowing prototropic tautomerism in this way, non-zwitterionic tautomers (3-amino-7-iminoindolizin-1-ones) were rejected by nuclear Overhauser effect spectroscopy experiments.

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“…The authors have cited additional references within the Supporting Information. [25][26][27][28][29][30][31][32][33]…”

Section: Supporting Informationmentioning

confidence: 99%

[3+2]‐Cycloaddition Reactions of gem‐Difluorocyclopropenes with Azomethine Ylides – Access to Novel Fluorinated Scaffolds

Donnelly

Singh

Tuttle

et al. 2023

Chemistry A European J

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The introduction of fluorinated moieties into drugs as well as the increase of their overall three‐dimensionality have become key strategies amongst medicinal chemists to generate sets of compounds with favorable drug‐like properties. However, the introduction of fluorinated cyclopropane ring systems which combines both strategies is not widely exploited to date. This paper reports synthetic strategies exploiting the reactivity of gem‐difluorocyclopropenes in dipolar cycloaddition reactions with azomethine ylides to afford sets of new fluorine‐containing 3‐azabicyclo[3.1.0]hexanes. In addition, the unexpected formation of complex trifluorinated scaffolds arising from proline esters and gem‐difluorocyclopropenes is highlighted along with computational studies to elucidate the underlying mechanism. This study presents new avenues towards pharmaceutically relevant fluorinated 3‐azabicyclo[3.1.0]hexanes that are accessible via robust and short synthetic sequences.

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Monosubstituted 3,3‐Difluorocyclopropenes as Bench‐Stable Reagents: Scope and Limitations

Cited by 6 publications

References 56 publications

A highly diastereoselective strain-release Doyle–Kirmse reaction: access to functionalized difluoro(methylene)cyclopropanes

A highly diastereoselective strain-release Doyle–Kirmse reaction: access to functionalized difluoro(methylene)cyclopropanes

Indolizin-1-ols with Charged Electron Acceptors: A Direct Way to 3H-Indolizinium-1-olates with Donor Functions

[3+2]‐Cycloaddition Reactions of gem‐Difluorocyclopropenes with Azomethine Ylides – Access to Novel Fluorinated Scaffolds

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