Fluoromethyl Phenyl Sulfoxide1

[65325-68-0]  · C7H7FOS  · Fluoromethyl Phenyl Sulfoxide  · (MW 158.21)

(synthesis of fluoro ketones,1b,2 fluoroalkenes,2,3 and aziridines4)

Physical Data: bp 75 °C/0.3 mmHg; n22D 1.5375.

Solubility: sol THF, CH2Cl2, CHCl3.

Preparative Methods: by the oxidation of Fluoromethyl Phenyl Sulfide with either N-Bromosuccinimide or m-Chloroperbenzoic Acid (eq 1).1c-f Studies of the structure of fluoro(phenylsulfinyl)methyllithium, investigated by NMR, suggest that lithium is bound to oxygen, rather than to the a-carbon atom.5

Purification: pure compound is obtained either by distillation or column chromatography on silica using hexane-ethyl acetate (1:4).

Handling, Storage, and Precautions: use in a fume hood.

Fluoro Ketones.

The reaction of fluoro(phenylsulfinyl)methyllithium, generated with Lithium Diisopropylamide, with aldehydes gives the corresponding a-fluoro-b-hydroxy sulfoxides, which upon pyrolysis give fluoromethyl ketones (eq 2).1b,2

a-Fluoro-1,3-keto sulfoxides, prepared from the addition of alkylated a-fluoromethyl phenyl sulfoxide carbanion to aldehydes followed by Swern oxidation (Dimethyl Sulfoxide-Oxalyl Chloride), undergo desulfinylation with Ethylmagnesium Bromide to give a-fluoro ketones (eq 3).6 Pyrolysis of the a-fluoro-1,3-keto sulfoxides gives a-fluoro-a,b-unsaturated ketones (eq 3).6 Dienones can be prepared by this procedure and the product undergoes the Nazarov cyclization to give 2-fluoro-2-cyclopenten-1-one (eq 4).6b


Fluoro(phenylsulfinyl)methyllithium can be alkylated with alkyl iodides or reactive alkyl bromides to give monoalkylated products which upon pyrolysis afford vinyl fluorides (eq 5).2 The addition of the a-fluoromethyl-N-methyl(phenyl)sulfoximine carbanion, derived from a-fluoromethyl phenyl sulfoxide, to carbonyl compounds gives a-fluoro-b-hydroxy(phenyl)sulfoximine adducts, which upon reductive desulfinylation with Aluminum Amalgam yield fluoroalkenes (eqs 6 and 7).3c

a-Substituted a-fluoro phenyl sulfoxides, prepared from thioacetals (eq 8)3b or from the corresponding sulfoxides, are used in the synthesis of fluoroalkenes (eqs 9 and 10).3d,7

Fluoro(phenylsulfinyl)methyllithium adds to aryl imines to give phenylsulfinylaziridines as a mixture of isomers (eq 11). This method is complementary to the reaction employing chloro(phenylsulfinyl)methyllithium.4

1. (a) Schlosser, M. T 1978, 34, 3. (b) Rozen, S.; Filler, R. T 1985, 41, 1111. (c) More, K. M.; Wemple, J. S 1977, 791. (d) McCarthy, J. R.; Peet, N. P.; LeTourneau, M. E.; Inbasekaran, M. JACS 1985, 107, 735. (e) Wnuk, S. F.; Robins, M. J. JOC 1990, 55, 4757. (f) Robins, M. J.; Wnuk, S. F. JOC 1993, 58, 3800.
2. Reutrakul, V.; Rukachaisirikul, V. TL 1983, 24, 725.
3. (a) Burton, D. J.; Greenlimb, P. E. JOC 1975, 40, 2796. (b) Purrington, S. T.; Pittman, J. H. TL 1987, 28, 3901. (c) Boy, M. L.; Collington, E. W.; Finch, H.; Swanson, S.; Whitehead, J. F. TL 1988, 29, 3365. (d) Satoh, T.; Itoh, N.; Onda, K. I.; Kitoh, Y.; Yamakawa, K. TL 1992, 33, 1483.
4. Mahidol, C.; Reutrakul, V.; Prapansiri, V.; Panyachotipun, C. CL 1984, 969.
5. Nájera, C.; Yus, M.; Hässig, R.; Seebach, D. HCA 1984, 67, 1100.
6. (a) Satoh, T.; Onda, K.; Itoh, N.; Yamakawa, K. TL 1991, 32, 5599. (b) Satoh, T.; Itoh, N.; Onda, K. I.; Kitoh, Y.; Yamakawa, K. BCJ 1992, 65, 2800.
7. (a) Krishnan, G.; Sampson, P. TL 1990, 31, 5609. (b) McCarthy, J. R.; Jarvi, E. T.; Matthews, D. P.; Edward, M. L.; Prakash, N. J.; Bowlin, T. L.; Mehdi, S.; Sunkara, P. S.; Bey, P. JACS 1989, 111, 1127. (c) Jarvi, E. T.; McCarthy, J. R.; Mehdi, S.; Matthews, D. P.; Edwards, M. L.; Prakash, N. J.; Bowlin, T. L.; Sunkara, P. S.; Bey, P. JMC 1991, 34, 647.

Vichai Reutrakul & Manat Pohmakotr

Mahidol University, Bangkok, Thailand

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