Rearrangements accompanying fluorination of 2-amino alcohols and 1,2-diols with Deoxo-Fluor™

Ye, Chengfeng; Shreeve, Jean’ne M.

doi:10.1016/j.jfluchem.2004.06.013

Cited by 33 publications

(17 citation statements)

References 16 publications

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“…Selective fluorination of multiple alcohols, especially the symmetrical diols, using common deoxyfluorination reagents such as DAST, is a challenging synthetic task4647. To date, available examples for selective deoxyfluorination of 1,2- and 1,3-diols mainly depend on the employment of sterically hindered reagents or reagents that can in situ generate stable hydroxyl protection groups1718224849.…”

Section: Resultsmentioning

confidence: 99%

Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

Wang

et al. 2016

Nat Commun

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Aromatic cation activation is a useful strategy to promote deoxyfunctionalization; however, the deoxyfluorination of alcohols with cyclopropenium cation remains an unsolved problem due to the weak nucleophilicity of fluoride ion. Here we report the use of 3,3-difluoro-1,2-diarylcyclopropenes (CpFluors) as easily accessible and reactivity-tunable deoxyfluorination reagents. The electronic nature of CpFluors is critical for fluorination of monoalcohols via alkoxycyclopropenium cations, and CpFluors with electron-rich aryl substituents facilitate the transformation with high efficiency; however, selective monofluorination of 1,2- and 1,3-diols, which proceeds via cyclopropenone acetals, is less dependent on the electronic nature of CpFluors. Moreover, CpFluors are more sensitive to the electronic nature of alcohols than many other deoxyfluorination reagents, thus fluorination of longer diols can be achieved selectively at the relatively electron-rich position. This research not only unveils the first example of deoxyfluorination reagents that contain an all-carbon scaffold, but also sheds light on the divergent reactivity of cyclopropenium cation in deoxyfunctionalization of alcohols.

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Section: Resultsmentioning

confidence: 99%

Deoxyfluorination of alcohols with 3,3-difluoro-1,2-diarylcyclopropenes

Wang

et al. 2016

Nat Commun

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“…The synthesis of piperidines A2, B2 and A3, B3, has been envisaged from 4-aminoprolinols C through aziridinium intermediates D, which would lead, after a nucleophilic attack, to the desired piperidines E or F (Scheme 1). [12] To be successful in synthesizing 3-substituted piperidines by ring enlargement of prolinols, the nitrogen of these latter has to be substituted by an alkyl group (PG 1 ). We have to point out that the synthesis of difluoropiperidines A3 and B3 has been envisaged from aminoprolinols C by ring expansion through aziridinium intermediates D, oxidation of the obtained piperidines F followed by difluorination of ketopiperidines G (Scheme 1).…”

Section: Synthesis Of Piperidines a And Bmentioning

confidence: 99%

Enantioselective Synthesis and Physicochemical Properties of Libraries of 3‐Amino‐ and 3‐Amidofluoropiperidines

Orliac

Routier

Charvillon

et al. 2014

Chemistry A European J

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The enantioselective syntheses of 3-amino-5-fluoropiperidines and 3-amino-5,5-difluoropiperidines were developed using the ring enlargement of prolinols to access libraries of 3-amino- and 3-amidofluoropiperidines. The study of the physicochemical properties revealed that fluorine atom(s) decrease(s) the pKa and modulate(s) the lipophilicity of 3-aminopiperidines. The relative stereochemistry of the fluorine atoms with the amino groups at C3 on the piperidine core has a small effect on the pKa due to conformationnal modifications induced by fluorine atom(s). In the protonated forms, the C-F bond is in an axial position due to a dipole-dipole interaction between the N-H(+) and C-F bonds. Predictions of the physicochemical properties using common software appeared to be limited to determine correct values of pKa and/or differences of pKa between cis- and trans-3-amino-5-fluoropiperidines.

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“…It has been reported that b-hydroxy-a-amino acid esters rearrange to afluoro-b-amino acid esters [7] and that 2-alkyl-2-amino alcohols rearrange to 2-alkyl-2-fluoro amines upon treatment with Deoxo-Fluor. [8] Other examples consist of the neighbouring group participation of the indole nucleus in the 3,4-migration of 4-indolyl-3-hydroxypiperidines, [9] the ring expansion of bicyclic epoxy alcohols toward fluorovinyl ethers, [10] the rearrangement of 2-azabicycloA C H T U N G T R E N N U N G [2.2.0]hexan-6-ols to 5-fluoro-2-azabicyclo-[2.1.1]hexanes [11] and the rearrangement of b-methoxy homoallyl alcohols to a,bunsaturated aldehydes. [12] The DAST-mediated 1,2-migrations, 1,4-migrations and 1,6-migrations of the anomeric substituent of saccharides, with or without ring contraction, are of special importance in biological studies of deoxofluorinated analogues of carbohydrates.…”

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confidence: 99%