Synthesis of <i>gem‐</i>Difluorinated Cyclopropanes and Cyclopropenes: Trifluoromethyltrimethylsilane as a Difluorocarbene Source

Wang, Fei; Luo, Tao; Hu, Jinbo; Wang, Ying; Krishnan, Hema S.; Jog, Parag V.; Ganesh, Sivagini; Prakash, G. K. Surya; Oláh, George A.

doi:10.1002/anie.201101691

Cited by 308 publications

(220 citation statements)

References 45 publications

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“…During the course of our studies, we noticed that 3,3-difluorocyclopropenes can be hydrolyzed to cyclopropenones upon prolonged storage in a wet atmosphere and that their stability towards water is closely related to their molecular structures353637. On the basis of these findings, we have initiated a program aiming to use the safe and readily available difluorocarbene reagents for deoxyfluorination by virtue of 3,3-difluorocyclopropenes.…”

Section: Resultsmentioning

confidence: 93%

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: 93%

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

Wang

et al. 2016

Nat Commun

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“…Thus, the treatment of the Sondheimer diyne 2a or 2,9-dibutoxy-substituted DIBOD ( 2b ) with 1 equivalent of trifluoromethyltrimethylsilane 15 and sodium iodide in dilute THF, followed by silica gel - promoted hydrolysis afforded the mono-caged diyne in 70% yield (Scheme 3). …”

Section: Resultsmentioning

confidence: 99%

Sequential Photochemistry of Dibenzo[a,e]dicyclopropa[c,g][8]annulene-1,6-dione: Selective Formation of Didehydrodibenzo[a,e][8]annulenes with Ultrafast SPAAC Reactivity

Sutton

Popik

2016

J. Org. Chem.

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An order of magnitude difference in photo-reactivity between bis- (photo-DIBOD, 1) and mono-cyclopropenone - caged dibenzocyclooctadiynes (MC-DIBOD, 5) allows for selective mono-decarbonylation of 1. Alternatively, 5 is prepared by selective mono-cyclopropanation of dibenzo[a, e]cyclooctadiyne. MC-DIBOD (5) permits efficient sequential SPAAC cross-linking of azide-derivatized substrates. Cycloaddition to 5 converts an azide moiety into a photo-caged form of triazole-fused dibenzo[a, e]cyclooctyne (3). While azide reactivity MC-DIBOD (5) and dibenzo[a, e] cyclooctadiyne (DIBOD, 2) is similar to other cyclooctynes, fusion of triazole to dibenzocyclooctyne system in 3 results in three orders of magnitude enhancement in SPAAC rates. In methanol, 3 reacts with butyl azide at an astonishing rate of 34 M−1s−1, thus representing the most reactive cyclooctyne analog reported so far. MC-DIBOD (5) was utilized in the preparation of mixed bis-triazoles and derivatization of the protein (BSA) with fluorescent dye and polyethylene glycol.

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“…14,27 Standard protocols for the generation of difluorocarbene require elevated temperature and harsh conditions 28 that are not compatible with the highly sensitive diynes 2a–c . The milder conditions of the recently developed Hu-Prakash reaction 29 allow for the efficient formation of difluorocarbene without significant decomposition of the substrate. Treatment of diynes 2a,b,d with TMSCF 3 resulted in the formation of the bis-difluorocyclopropenes 4a,b,d , which were subsequently hydrolyzed on wet silica gel to afford the target bis-cyclopropenones 1a–c (Scheme 2).…”

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confidence: 99%

Cyclopropenone-caged Sondheimer diyne (dibenzo[a,e]cyclooctadiyne): a photoactivatable linchpin for efficient SPAAC crosslinking

Sutton

Steet

et al. 2016

Chem. Commun.

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The first fully conjugated bis-cyclopropenone (photo-DIBOD), a derivative of dibenzo[a,e][8]annulene, has been synthesized. 350–420 nm irradiation of this robust compounds results in the efficient formation of dibenzo [a, e] cyclooctadiyne, an unstable, but useful SPAAC cross-linking reagent. Since photo-DIBO doesn’t react with organic azides, this method allows for the spatiotemporal control of the ligation of two azide-tagged substrates.

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Synthesis of gem‐Difluorinated Cyclopropanes and Cyclopropenes: Trifluoromethyltrimethylsilane as a Difluorocarbene Source

Cited by 308 publications

References 45 publications

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

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

Sequential Photochemistry of Dibenzo[a,e]dicyclopropa[c,g][8]annulene-1,6-dione: Selective Formation of Didehydrodibenzo[a,e][8]annulenes with Ultrafast SPAAC Reactivity

Cyclopropenone-caged Sondheimer diyne (dibenzo[a,e]cyclooctadiyne): a photoactivatable linchpin for efficient SPAAC crosslinking

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