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Organocatalyzed Trifluoromethylation of Ketones and Sulfonyl Fluorides by Fluoroform under a Superbase System.

Okusu S, Hirano K, Tokunaga E, Shibata N - ChemistryOpen (2015)

Bottom Line: The superbase organocatalytic system can also be applied to the trifluoromethylation of arylsulfonyl fluorides for biologically important aryl triflones in THF or DMF in good yields.Protonated P4-tBu, H[P4-tBu](+), is suggested to be crucial for the catalytic process.This new catalytic methodology using HCF3 is expected to expand the range of synthetic applications of trifluoromethylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Nanopharmaceutical Sciences, Department of Frontier Materials, Nagoya Institute of Technology Gokiso, Showa-ku, Nagoya, 466-8555, Japan.

ABSTRACT
Fluoroform (HCF3, HFC-23) is a side product in the manufacture of polytetrafluoroethylene (Teflon). Despite its attractive properties, taming HCF3 for trifluoromethylation is quite problematic owing to its low acidity and the lability of the naked trifluoromethyl carbanion generated from HCF3. Herein we report the organic-superbase-catalyzed trifluoromethylation of ketones and arylsulfonyl fluorides by HCF3. The reactions were carried out by using a newly developed "superbase organocatalyst system" consisting of catalytic amounts of P4-tBu and N(SiMe3)3. A series of aryl and alkyl ketones were converted into the corresponding α-trifluoromethyl carbinols in good yields under the organocatalysis conditions in THF. The superbase organocatalytic system can also be applied to the trifluoromethylation of arylsulfonyl fluorides for biologically important aryl triflones in THF or DMF in good yields. Protonated P4-tBu, H[P4-tBu](+), is suggested to be crucial for the catalytic process. This new catalytic methodology using HCF3 is expected to expand the range of synthetic applications of trifluoromethylation.

No MeSH data available.


Related in: MedlinePlus

Proposed catalytic process for the trifluoromethylation of 3 with HCF3 to aryl triflones 4 under the P4-tBu/N(SiMe3)3 system.
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fig02: Proposed catalytic process for the trifluoromethylation of 3 with HCF3 to aryl triflones 4 under the P4-tBu/N(SiMe3)3 system.

Mentions: We next extended the organocatalyzed trifluoromethylation reaction using HCF3 for the synthesis of aryl triflones, i.e., trifluoromethyl aryl sulfones.14 Aryl triflones are recognized as important structural units in bioactive molecules, chiral catalysts, and functional materials15 because of the unique properties of the SO2CF3 moieties, such as high electronegativity (σm=0.96) with moderate lipophilicity (π=0.55).16 To generate an optimal catalytic process, a new working hypothesis for the transformation should first be considered, as shown in Figure 2. The key to this transformation is the use of aryl fluorides 3. Specifically, after the initial formation of aryl triflones 4 from 3 and HCF3 with P4-tBu, H[P4-tBu]+ is formed as an ion pair with the fluoride ion, F−, which spontaneously attacks the silicon atom of N(SiMe3)3 to form F-SiMe3 and [N(SiMe3)2]−. Regeneration of P4-tBu by [N(SiMe3)2]− should be difficult (route a); thus [N(SiMe3)2]− should remove the proton of HCF3 with the help of H[P4-tBu]+ to regenerate the ion pair of H[P4-tBu]+ and F−. H[P4-tBu]+ acts directly as a true catalyst on the reaction cycle (route b), as predicted for the trifluoromethylation of ketones in Figure 1.


Organocatalyzed Trifluoromethylation of Ketones and Sulfonyl Fluorides by Fluoroform under a Superbase System.

Okusu S, Hirano K, Tokunaga E, Shibata N - ChemistryOpen (2015)

Proposed catalytic process for the trifluoromethylation of 3 with HCF3 to aryl triflones 4 under the P4-tBu/N(SiMe3)3 system.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608523&req=5

fig02: Proposed catalytic process for the trifluoromethylation of 3 with HCF3 to aryl triflones 4 under the P4-tBu/N(SiMe3)3 system.
Mentions: We next extended the organocatalyzed trifluoromethylation reaction using HCF3 for the synthesis of aryl triflones, i.e., trifluoromethyl aryl sulfones.14 Aryl triflones are recognized as important structural units in bioactive molecules, chiral catalysts, and functional materials15 because of the unique properties of the SO2CF3 moieties, such as high electronegativity (σm=0.96) with moderate lipophilicity (π=0.55).16 To generate an optimal catalytic process, a new working hypothesis for the transformation should first be considered, as shown in Figure 2. The key to this transformation is the use of aryl fluorides 3. Specifically, after the initial formation of aryl triflones 4 from 3 and HCF3 with P4-tBu, H[P4-tBu]+ is formed as an ion pair with the fluoride ion, F−, which spontaneously attacks the silicon atom of N(SiMe3)3 to form F-SiMe3 and [N(SiMe3)2]−. Regeneration of P4-tBu by [N(SiMe3)2]− should be difficult (route a); thus [N(SiMe3)2]− should remove the proton of HCF3 with the help of H[P4-tBu]+ to regenerate the ion pair of H[P4-tBu]+ and F−. H[P4-tBu]+ acts directly as a true catalyst on the reaction cycle (route b), as predicted for the trifluoromethylation of ketones in Figure 1.

Bottom Line: The superbase organocatalytic system can also be applied to the trifluoromethylation of arylsulfonyl fluorides for biologically important aryl triflones in THF or DMF in good yields.Protonated P4-tBu, H[P4-tBu](+), is suggested to be crucial for the catalytic process.This new catalytic methodology using HCF3 is expected to expand the range of synthetic applications of trifluoromethylation.

View Article: PubMed Central - PubMed

Affiliation: Department of Nanopharmaceutical Sciences, Department of Frontier Materials, Nagoya Institute of Technology Gokiso, Showa-ku, Nagoya, 466-8555, Japan.

ABSTRACT
Fluoroform (HCF3, HFC-23) is a side product in the manufacture of polytetrafluoroethylene (Teflon). Despite its attractive properties, taming HCF3 for trifluoromethylation is quite problematic owing to its low acidity and the lability of the naked trifluoromethyl carbanion generated from HCF3. Herein we report the organic-superbase-catalyzed trifluoromethylation of ketones and arylsulfonyl fluorides by HCF3. The reactions were carried out by using a newly developed "superbase organocatalyst system" consisting of catalytic amounts of P4-tBu and N(SiMe3)3. A series of aryl and alkyl ketones were converted into the corresponding α-trifluoromethyl carbinols in good yields under the organocatalysis conditions in THF. The superbase organocatalytic system can also be applied to the trifluoromethylation of arylsulfonyl fluorides for biologically important aryl triflones in THF or DMF in good yields. Protonated P4-tBu, H[P4-tBu](+), is suggested to be crucial for the catalytic process. This new catalytic methodology using HCF3 is expected to expand the range of synthetic applications of trifluoromethylation.

No MeSH data available.


Related in: MedlinePlus