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

Fluoroalkenes.

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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