Fluorination by sulfur tetrafluoride

Main functional group conversions

Carboxylic acids, amides, esters, and carboxylate salts convert to the trifluoromethyl derivatives, although conditions vary widely: : For carboxlic acids, the first step gives the acyl fluorides, in keeping with the tendency of SF4 to fluorinate acidic hydroxyl groups: : Similarly SF4 converts sulfonic acids to sulfonyl fluorides: : Aldehydes and ketones convert to geminal difluorides: : Alcohols convert to alkyl fluorides, although this conversion works best with acidic alcohols, such as fluorinated alcohols: :

Mechanism

The mechanism of fluorination by SF4 is assumed to resemble chlorination by phosphorus pentachloride. Hydrogen fluoride, a useful solvent for these reactions, activates SF4: : Species of the type ROSF3 are often invoked as intermediates. In the case of aldehydes and ketones, SF4 is thought to initially add across the double bond to give R2CFOSF3.

Examples

A solution of sulfur tetrafluoride in hydrogen fluoride converts hydroxy-containing amino acids to the fluoro amino acids:

When vicinal diols are combined with SF4, difluorination occurs with inversion of configuration at only one of the alcohols. This was demonstrated in the synthesis of meso-difluorosuccinate from (L)-tartrate and the synthesis of (D)- and (L)-difluorosuccinate from meso-tartrate.

Carbonyl compounds generally react with SF4 to yield geminal difluorides. Reaction times tend to be on the order of hours and yields are moderate. Fluorination of lactones can provide heterocyclic fluorides, although ring opening has been observed for γ-butyrolactone. The six-membered lactide does not experience ring opening.

Fluorination opens epoxides to give either geminal or vicinal difluorides in most cases. Monoarylepoxides give geminal products with migration of the aryl group. Yields are low for sterically hindered di- and trisubstituted epoxides. Epoxides substituted with an ester group give vicinal difluorides via an alkoxysulfur trifluoride intermediate.

Carboxylic acids react with SF4 to afford trifluoromethyl compounds:{{OrgSynth | author = Hasek, W. R. : The formation of the trifluoromethyl derivative sometimes competes with formation of tetrafluoroalkyl ethers, which arise from the reaction between difluoromethyl cation and acyl fluoride.

Sulfur tetrafluoride can be used to fluorinate polymers efficiently. This often has a profound effect on polymer properties—fluorination of polyvinyl alcohol, for instance, improves its resistance to strong acids and bases.

A prostaglandin bearing a trifluoromethyl group at C-16 is prepared using sulfur tetrafluoride.

Related reagents

For small scale reactions, SF4 can be inconvenient since it is a gas and stainless steel reaction vessels are required. Many transformations require elevated temperatures. The reaction generates hydrogen fluoride. These concerns have led to interest in alternative fluorinating reagents. Selenium tetrafluoride, a liquid at room temperature, behaves similarly to SF4. Diethylaminosulfur trifluoride (DAST) is a derivative of SF4 that is easier to handle, albeit more expensive.

References

References

1. (1985). "Organic Reactions".
2. (2011). "Organic Reactions".
3. (1975). "Selective Fluorination of Hydroxy Amines and Hydroxy Amino Acids with Sulfur Tetrafluoride in Liquid Hydrogen Fluoride". The Journal of Organic Chemistry.
4. Bell, M.; Hudlicky, M. ''J. Fluorine Chem.'' '''1980''', ''15'', 191.
5. Mobbs, H. ''J. Fluorine Chem.'' '''1971''', ''1'', 361.
6. Muratov, N.; Burmakov, I.; Kunshenko, V.; Alekseeva, A.; Yagupol'skii, M. ''J. Org. Chem. USSR (Engl. Transl.)'' '''1982''', ''18'', 1220.
7. Yagupol'skii, M.; Golikov, I.; Alekseeva, A.; Aleksandrov, M. ''J. Org. Chem. USSR (Engl. Transl.)'' '''1971''', ''7'', 737.
8. Dmowski, W.; Kolinski, A. ''Rocz. Chem.'' '''1974''', ''48'', 1697.
9. Dmowski, W.; Kolinski, A. ''Pol. J. Chem.'' '''1978''', ''52'', 547.
10. Bezsolitsen, P.; Gorbunov, N.; Nazarov, A.; Khardin, P. ''Vysokomol. Soedin., Ser. A'' '''1972''', ''14'', 950 [C.A., 77, 75710e (1972)].
11. Holland, G. W.; Jernow, J. L.; Rosen, P. U.S. Pat. 4,256,911 (1981) [C.A., 89, 146500x (1978)].
12. {{March6th
13. (2006). "Encyclopedia of Reagents for Organic Synthesis".