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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

Catalytic trifluoromethylation of ketones 1 and sulfonyl fluorides 3 by HCF3 under the organocatalytic superbase system, P4-tBu/N(SiMe3)3.
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sch01: Catalytic trifluoromethylation of ketones 1 and sulfonyl fluorides 3 by HCF3 under the organocatalytic superbase system, P4-tBu/N(SiMe3)3.

Mentions: Fluoroform (HCF3, HFC-23) is a side product in the manufacture of polytetrafluoroethylene (Teflon). In view of its attractive properties (ozone friendly, nontoxic, and inexpensive), it is not surprising that there have been many attempts to use HCF3 for trifluoromethylation reactions.6 However, taming HCF3 is quite problematic due to its low acidity (pKa=27 in H2O) and the lability of the naked trifluoromethyl carbanion generated from HCF3.7 During the last five years, the chemistry of HCF3 has made significant progress with the use of organometallics as represented by Cu (Grushin), K (Prakash), and others.8 In late 2012, we reported that a sterically demanding organic superbase, 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phosphoranylidenamino]-2λ,5,4λ,5-catenadi(phosphazene) (P4-tBu) effectively generates a trifluoromethyl carbanion from HCF3 without decomposition to difluorocarbene that undergoes successful addition to aromatic aldehydes, ketones, and disulfides.9 Our method does not require organometallics, and the corresponding trifluoromethylation products are obtained in good to high yields. However, this reaction needs a stoichiometric amount of P4-tBu. The development of efficient organocatalytic processes for HCF3 trifluoromethylation is considered to be one of the greatest challenges in fluorine chemistry. The seminal work by Langlois and co-workers6e on trifluoromethylation with HCF3 clearly illustrates the validity of this approach. Herein we disclose a catalytic version of this HCF3 trifluoromethylation. The key to this catalytic reaction is the combination of organic superbases. A wide variety of diaryl, aryl-alkyl, and dialkyl ketones 1 are nicely trifluoromethylated by HCF3 under a newly developed “superbase-organocatalysis” of P4-tBu/N(SiMe3)3 in THF to provide a wide range of trifluoromethylated carbinols 2. This superbase organocatalytic system consisting of P4-tBu and N(SiMe3)3 also realized a catalytic trifluoromethylation of arylsulfonyl fluorides 3 with HCF3 in THF or DMF to furnish biologically important fluorinated compounds of aryltriflones 4 in good yields (Scheme 1). Protonated P4-tBu (H[P4-tBu]+) is suggested to be crucial for the catalytic process.


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

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

Catalytic trifluoromethylation of ketones 1 and sulfonyl fluorides 3 by HCF3 under the organocatalytic superbase system, P4-tBu/N(SiMe3)3.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

sch01: Catalytic trifluoromethylation of ketones 1 and sulfonyl fluorides 3 by HCF3 under the organocatalytic superbase system, P4-tBu/N(SiMe3)3.
Mentions: Fluoroform (HCF3, HFC-23) is a side product in the manufacture of polytetrafluoroethylene (Teflon). In view of its attractive properties (ozone friendly, nontoxic, and inexpensive), it is not surprising that there have been many attempts to use HCF3 for trifluoromethylation reactions.6 However, taming HCF3 is quite problematic due to its low acidity (pKa=27 in H2O) and the lability of the naked trifluoromethyl carbanion generated from HCF3.7 During the last five years, the chemistry of HCF3 has made significant progress with the use of organometallics as represented by Cu (Grushin), K (Prakash), and others.8 In late 2012, we reported that a sterically demanding organic superbase, 1-tert-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)phosphoranylidenamino]-2λ,5,4λ,5-catenadi(phosphazene) (P4-tBu) effectively generates a trifluoromethyl carbanion from HCF3 without decomposition to difluorocarbene that undergoes successful addition to aromatic aldehydes, ketones, and disulfides.9 Our method does not require organometallics, and the corresponding trifluoromethylation products are obtained in good to high yields. However, this reaction needs a stoichiometric amount of P4-tBu. The development of efficient organocatalytic processes for HCF3 trifluoromethylation is considered to be one of the greatest challenges in fluorine chemistry. The seminal work by Langlois and co-workers6e on trifluoromethylation with HCF3 clearly illustrates the validity of this approach. Herein we disclose a catalytic version of this HCF3 trifluoromethylation. The key to this catalytic reaction is the combination of organic superbases. A wide variety of diaryl, aryl-alkyl, and dialkyl ketones 1 are nicely trifluoromethylated by HCF3 under a newly developed “superbase-organocatalysis” of P4-tBu/N(SiMe3)3 in THF to provide a wide range of trifluoromethylated carbinols 2. This superbase organocatalytic system consisting of P4-tBu and N(SiMe3)3 also realized a catalytic trifluoromethylation of arylsulfonyl fluorides 3 with HCF3 in THF or DMF to furnish biologically important fluorinated compounds of aryltriflones 4 in good yields (Scheme 1). Protonated P4-tBu (H[P4-tBu]+) is suggested to be crucial for the catalytic process.

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