Allyl Phenyl Sulfide1

[5296-64-0]  · C9H10S  · Allyl Phenyl Sulfide  · (MW 150.24)

(metalated derivatives are ambident nucleophiles; undergo reductive lithiation; precursors to sulfonium salts and sulfur ylides which undergo rearrangement)

Physical Data: bp 48-49 °C/0.43 mmHg; d 1.0220 g cm-3.

Solubility: insol water; sol most organic solvents.

Form Supplied in: colorless liquid of 98% purity as obtained commercially.

Preparative Method: from Allyl Bromide and sodium thiophenolate in ethanol.2

Purification: distillation in vacuo prior to use.

Handling, Storage, and Precautions: must be handled in a fume hood due to stench caused by contamination with Thiophenol. The pure sulfide has a more agreeable odor with a sweet overtone. No special precautions are necessary when handling in the atmosphere for weighing and transferring. In order to avoid autoxidation the sulfide should be stored in a well sealed vessel with exclusion of oxygen and moisture at 4 °C.

Metalation.

Treatment of allyl and alkylallyl phenyl sulfides with n-Butyllithium in THF gives lithiated reagents which predominantly react with alkyl halides in THF at C-a although substantial g-alkylation takes place in certain cases.1 a-Regioselectivity is enhanced by replacing phenyl with 2-pyridyl, thiazolyl, N-methylimidazolyl and others.1a,1d Hexamethylphosphoric Triamide decreases regioselectivity of alkylation.1a Lithiated prenyl phenyl sulfide adds to acetone primarily through C-a in the presence of [2.2.2]cryptate, whereas predominant addition through C-g takes place in the absence of additives; 1,4-Diazabicyclo[2.2.2]octane and N,N,N,N-Tetramethylethylenediamine have no effect on this regiochemistry.3 Transmetalation may also be used to enhance regioselectivity in carbonyl addition.1d Lithiated allyl phenyl sulfide upon transmetalation with Titanium Tetraisopropoxide adds through C-a with carbonyl compounds,4 and to a proline derivative (eq 1),5 although the lithiated reagent alone reacts in the same way with indene oxide.6 While the lithiated sulfide reacts with enones in THF at -78 °C to give mixtures of a- and g-carbonyl (or 1,2) adducts, HMPA (1.5 equiv.) induces kinetically controlled conjugate (or 1,4) addition through C-a.7 This observation has been exploited in syntheses of prostaglandins,8 and estra-1,3,5(10)-triene-6,11,17-trione.9 The conjugate addition of the lithiated sulfide to 3-methylbutenenitrile in the presence of HMPA proceeds through C-a.10 Stereoselectivity is rarely observed in addition reactions involving lithiated allyl phenyl sulfide, with exceptions being provided by the reactions involving 3-methylbutenenitrile10 and the transmetalated sulfide with carbonyl compounds4 and proline.5

Reductive Metalation.

Reductive lithiation with Lithium Naphthalenide or Lithium 1-(Dimethylamino)naphthalenide provides an efficient means of replacing the phenylthio group in a wide variety of substituted allyl phenyl sulfides with lithium to give allyllithium reagents not readily obtainable by other methods.11

Allylic Displacement.

Allyl phenyl sulfide undergoes displacement by Grignard reagents catalyzed by nickel phosphine complexes.12 However, regioselectivity in alkylallyl cases is poor. Treatment of allylic sulfides bearing a thiazoline substituent with Iodomethane generates allylic iodides, a reaction driven by formation of methyliminium intermediates (eq 2).13 Addition of alkyl radicals, generated from alkyl halides by a mixture of a cobalt(III) complex and zinc, to C-g of allyl phenyl sulfide (and sulfone, see Allyl Phenyl Sulfone) followed by loss of a phenylthio radical produces the alkylated product in high yield.14

Sigmatropic Rearrangements.

When the phenyl group is replaced by methylene attached to a charge-stabilizing group15 or a group capable of undergoing transmetalation with lithium,16 lithiation generates an a-lithiated species which undergoes [2,3]-thia-Wittig rearrangement to homoallylic thiols (eq 3). The use of sulfur cation radicals in organic synthesis is rare. However, the cation radical derived from allyl phenyl sulfide and Cerium(IV) Ammonium Nitrate couples with silyl enol ethers to give a sulfonium adduct which rearranges to g,d-alkenyl-a-phenylthio ketones in high yields (eq 4).17 Rearrangement of sulfonium ylides generated by the addition of carbenes to allyl sulfides proceeds to give (E)-homoallylic sulfides;1b,1c,18 chirality in relevant cases is thereby transferred from C-1 to C-3 (eq 5).19 Allyl phenyl sulfide undergoes Lewis acid-catalyzed conjugate addition to propiolic esters to give sulfonium allenes which rearrange to a-allyl-b-phenylthiovinyl esters.20 The sulfide and related compounds also undergo a catalyzed [3,3]-thio-Claisen rearrangement to give o-allylbenzenethiols.1b,21

Related Reagents.

Allyl Phenyl Selenide; Allyl Phenyl Sulfone; Allyl Phenyl Sulfoxide.


1. (a) Evans, D. A.; Andrews, G. C. ACR, 1974, 7, 147. (b) Trost, B. M.; Melvin, L. S. Sulfur Ylides. Emerging Synthetic Intermediates; Academic Press: New York, 1975. (c) Block, E. Reactions of Organosulfur Compounds; Academic Press: New York, 1978. (d) Biellmann, J.-F.; Ducep, J.-B. OR, 1982, 27, 1. (e) Werstiuk, N. H. T, 1983, 39, 205.
2. Hurd, C. D.; Greengard, H. JACS, 1930, 52, 3356.
3. Atlani, P. M.; Biellmann, J.-F.; Dube, S.; Vicens, J. J. TL, 1974, 2665.
4. Ikeda, Y.; Furuta, K.; Meguriya, N.; Ikeda, N.; Yamamoto, H. JACS, 1982, 104, 7663. Furuta, K.; Ikeda, Y.; Meguriya, N.; Ikeda, N.; Yamamoto, H. BCJ, 1984, 57, 2781.
5. St.-Denis, Y.; Chan, T.-H. JOC, 1992, 57, 3078.
6. Phialas, M.; Sammes, P. G.; Kennewell, P. D.; Westwood, R. JCS(P1), 1984, 687.
7. Binns, M. R.; Haynes, R. K.; Houston, T. L.; Jackson, W. R. TL, 1980, 21, 573. Binns, M. R.; Haynes, R. K. JOC, 1981, 46, 3790. Haynes, R. K.; Schober, P. A.; Binns, M. R. AJC, 1987, 40, 1223. Binns, M. R.; Haynes, R. K. AJC, 1987, 40, 937. Vasil'eva, L. L.; Mel'nikova, V. I.; Gainullina, E. T.; Pivnitskii, K. K. JOU, 1983, 19, 835.
8. Nokami, J.; Ono, T.; Iwao, A.; Wakabayashi, S. BCJ, 1982, 55, 3043. Binns, M. R.; Haynes, R. K.; Lambert, D. E.; Schober, P. A. TL, 1985, 26, 3385. Haynes, R. K.; Lambert, D. E.; Schober, P. A.; Turner, S. G.; AJC, 1987, 40, 1211. Haynes, R. K.; Schober, P. A. AJC, 1987, 40, 1249.
9. Jones, D. N.; Peel, M. R. CC, 1986, 216.
10. Lambs, L.; Singh, N. P.; Biellmann, J.-F. JOC, 1992, 57, 6301. Lambs, L.; Singh, N. P.; Biellmann, J.-F. TL, 1991, 32, 2637.
11. Guo, B.-S.; Doubleday, W.; Cohen, T. JACS, 1987, 109, 4710. Cohen, T.; Bhupathy, M. ACR, 1989, 22, 152.
12. Okamura, H.; Takei, H. TL, 1979, 3425.
13. Hirai, K.; Kishida, Y. TL, 1972, 2743. Hirai, K.; Kishida, Y. OSC, 1988, 6, 704. Hirai, K.; Kishida, Y. H, 1974, 2, 185.
14. Giese, B.; Erdmann, P.; Göbel, T.; Springer, R. TL, 1992, 33, 4545.
15. Rautenstrauch, V. HCA, 1971, 54, 739. Huynh, C.; Ratovelomanana, V. Julia, S.; CR(C), 1975, 280, 1231. Snider, B. B.; Hrib, N. J.; Fuzesi, L. JACS, 1976, 98, 7115. Huynh, C.; Julia, S. SC, 1977, 7, 103.
16. Von der Emde, H.; Brückner, R. TL, 1992, 33, 7323.
17. Narasaka, K.; Okauchi, T. CL, 1991, 515.
18. Parham, W. E.; Groen, S. H. JOC, 1964, 29, 2214. Parham, W. E.; Groen, S. H. JOC, 1965, 30, 728. Parham, W. E.; Groen, S. H. JOC, 1966, 31, 1694.
19. Hartley, R. C.; Warren, S.; Richards, I. C. TL, 1992, 33, 8155.
20. Hayakawa, K.; Kamikawaji, Y.; Wakita, A.; Kanematsu, K. JOC, 1984, 49, 1985.
21. Kwart, H. Schwartz, J. L. JOC, 1974, 39, 1575 and references cited.

Richard K. Haynes

Hong Kong University of Science and Technology, Hong Kong

Simone C. Vonwiller

The University of Sydney, NSW, Australia



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