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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

Trifluoromethylation of ketones 1 by HCF3. Yield values shown are for isolated product. [a] P4-tBu used at 30 mol %.
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sch02: Trifluoromethylation of ketones 1 by HCF3. Yield values shown are for isolated product. [a] P4-tBu used at 30 mol %.

Mentions: With suitable conditions in hand, the scope of trifluoromethylation of ketones 1 using HCF3 was explored with a variety of substrates selected in order to establish the generality of the process (Scheme 2). Aromatic rings substituted with either electron-donating or -withdrawing substituents, such as methoxy and chloro, were tolerated independent of the substituted positions on the benzene ring (2 b and 2 c–f). A heteroaromatic di(2-pyridyl) ketone was compatible with the same reaction conditions to provide 2 g in 72 % yield. The corresponding trifluoromethylated carbinols (2 h and 2 i) from cyclic ketones were obtained in good isolated yields. Furthermore, the alkyl-substituted ketones produced the desired products 2 j and 2 k in 71–76 % yield.


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

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

Trifluoromethylation of ketones 1 by HCF3. Yield values shown are for isolated product. [a] P4-tBu used at 30 mol %.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

sch02: Trifluoromethylation of ketones 1 by HCF3. Yield values shown are for isolated product. [a] P4-tBu used at 30 mol %.
Mentions: With suitable conditions in hand, the scope of trifluoromethylation of ketones 1 using HCF3 was explored with a variety of substrates selected in order to establish the generality of the process (Scheme 2). Aromatic rings substituted with either electron-donating or -withdrawing substituents, such as methoxy and chloro, were tolerated independent of the substituted positions on the benzene ring (2 b and 2 c–f). A heteroaromatic di(2-pyridyl) ketone was compatible with the same reaction conditions to provide 2 g in 72 % yield. The corresponding trifluoromethylated carbinols (2 h and 2 i) from cyclic ketones were obtained in good isolated yields. Furthermore, the alkyl-substituted ketones produced the desired products 2 j and 2 k in 71–76 % yield.

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