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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 1 with HCF3 under the P4-tBu/N(SiMe3)3 system.
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fig01: Proposed catalytic process for the trifluoromethylation of 1 with HCF3 under the P4-tBu/N(SiMe3)3 system.

Mentions: Figure 1 shows a proposed catalytic cycle for the trifluoromethylation of 1 with HCF3. As mentioned in our previous report,9 the CF3 adducts RCCF3(O−)R’ are initially formed as ion pairs with H[P4-tBu]+. Next, delivery of the trimethylsilyl group of N(SiMe3)3 to the alkoxides RCCF3(O−)R’ proceeds, providing trimethylsilyl ethers accompanied with the same amount of [N(SiMe3)2]−. The [N(SiMe3)2]− species might extract a proton from H[P4-tBu]+ to activate P4-tBu for a catalytic process (route a). However, activation of P4-tBu by deprotonation of H[P4-tBu]+ with [N(SiMe3)2]− should be difficult, given their basicity (P4-tBu pKBH: 28.0 (THF), 30.3 (DMSO); HN(SiMe3)2 pKa=25.8 (THF), 26 (DMSO)).13 Another possibility is that [N(SiMe3)2]− directly deprotonates HCF3, allowing a shunt catalytic cycle to provide the ion pairs of RCCF3(O−)R’ and H[P4-tBu]+ (route b). The alkoxides RCCF3(O−)R’ should attack the silyl group of N(SiMe3)3 to furnish products of trimethylsilyl ethers accompanied by the same amount of [N(SiMe3)2]− as an ion pair with H[P4-tBu]+. Hence, H[P4-tBu]+ should play an important role in this catalytic cycle. The H[P4-tBu]+ species forms a stabilized ion pair with the alkoxides RCCF3(O−)R’. This stabilization should be a driving force for the catalytic cycle mediated by [N(SiMe3)2]−, because no reaction was observed with the use of CsF instead of P4-tBu (Table 1, run 11).


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 1 with HCF3 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

fig01: Proposed catalytic process for the trifluoromethylation of 1 with HCF3 under the P4-tBu/N(SiMe3)3 system.
Mentions: Figure 1 shows a proposed catalytic cycle for the trifluoromethylation of 1 with HCF3. As mentioned in our previous report,9 the CF3 adducts RCCF3(O−)R’ are initially formed as ion pairs with H[P4-tBu]+. Next, delivery of the trimethylsilyl group of N(SiMe3)3 to the alkoxides RCCF3(O−)R’ proceeds, providing trimethylsilyl ethers accompanied with the same amount of [N(SiMe3)2]−. The [N(SiMe3)2]− species might extract a proton from H[P4-tBu]+ to activate P4-tBu for a catalytic process (route a). However, activation of P4-tBu by deprotonation of H[P4-tBu]+ with [N(SiMe3)2]− should be difficult, given their basicity (P4-tBu pKBH: 28.0 (THF), 30.3 (DMSO); HN(SiMe3)2 pKa=25.8 (THF), 26 (DMSO)).13 Another possibility is that [N(SiMe3)2]− directly deprotonates HCF3, allowing a shunt catalytic cycle to provide the ion pairs of RCCF3(O−)R’ and H[P4-tBu]+ (route b). The alkoxides RCCF3(O−)R’ should attack the silyl group of N(SiMe3)3 to furnish products of trimethylsilyl ethers accompanied by the same amount of [N(SiMe3)2]− as an ion pair with H[P4-tBu]+. Hence, H[P4-tBu]+ should play an important role in this catalytic cycle. The H[P4-tBu]+ species forms a stabilized ion pair with the alkoxides RCCF3(O−)R’. This stabilization should be a driving force for the catalytic cycle mediated by [N(SiMe3)2]−, because no reaction was observed with the use of CsF instead of P4-tBu (Table 1, run 11).

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