[22859-62-7]  · C7H7LiSe  · Phenylselenomethyllithium  · (MW 177.04)

(nucleophilic introduction of phenylselenomethyl group; used for one-carbon homologation of alkyl halides, conversion of aldehydes to terminal epoxides, oxetanes, and tetrahydrofurans; synthesis of terminal alkenes from alkyl halides or carbonyl compounds)

Solubility: sol THF-pentane or ether-pentane.

Preparative Methods: 1a,1d-1f,5 has been prepared by (i) metalation of methyl phenyl selenide with lithium amides or butyllithium-TMEDA,3,6 (ii) halogen-metal exchange from bromomethyl phenyl selenide and butyllithium,7 or (iii) Se-Li exchange from bis(phenylseleno)methane and n-Butyllithium (THF, -78 °C, method of choice).1b,2,3 The same reaction can be achieved in ether but requires the use of the more reactive s-Butyllithium.8

Handling, Storage, and Precautions: stable at 0 °C in THF for more than 10 h,2,3 but products resulting from its decomposition have been trapped in some cases at lower temperature even after a few minutes. Phenylselenomethyllithium seems to be in equilibrium with lithium benzeneselenolate and methylene.4 Use in a fume hood.

General Discussion.

Phenylselenomethyllithium reacts with alkyl halides to produce alkyl phenyl selenides,2,3 epoxides and oxetanes4 to produce 3-hydroxy- and 4-hydroxyalkyl phenyl selenides, respectively, and aldehydes and ketones to produce 2-hydroxyalkyl phenyl selenides.2,3,6-13

Alkylation has been successfully achieved with Iodomethane, primary alkyl halides, and terminal epoxides. In the latter two cases the presence of HMPA minimizes the products resulting from substitution of the electrophiles by lithium phenylselenolate (5% instead of 40%).4

Phenylselenomethyllithium adds to hindered or enolizable carbonyl compounds such as 2,2,6,6-tetramethylcyclohexanone or deoxybenzoin.13 Phenylselenomethyllithium mainly produces the alcohol resulting from equatorial attack on reaction with 4-t-butylcyclohexanone (THF, -78 °C, axial:equatorial alcohol = 85:15).11 It adds on the carbonyl group of enones if the reaction is carried out in THF and 1,4 in THF/HMPA.1,14-17 The latter conditions have been successfully used to produce a valuable intermediate in the synthesis of (+)-pederin from an a,b-unsaturated lactone.15,16

Phenylselenomethyllithium is a valuable reagent for homologation.1b Phenylselenoalkanes, prepared by alkylation of phenylselenomethyllithium, can be transformed to alkanes by reduction with Raney Nickel,18 Lithium-Ethylamine18 or, more conveniently, by Tri-n-butylstannane or Triphenylstannane (eq 1).19

The phenylseleno group can be replaced by iodide.20 The reaction proceeds through a selenonium salt, works with functionalized alkyl phenyl selenides such as 3-(hydroxy)nonyl phenyl selenide (eq 2),4 and allows the one-carbon homologation of primary alkyl halides.20 A wider range of nucleophiles (I-, Br-, Cl-, OH-, N3-, MeOH,21,22 PhS-, CN-) can be used23 if the selenide is oxidized to a selenone (eq 3).24 In the transformations reported (eqs 2 and 3), phenylselenomethyllithium has played alternatively the role of LiCH2X (X = halogen), LiCH2N3, LiCH2OH, LiCH2OMe, LiCH2SPh, and LiCH2CN, respectively.

Primary alkyl selenides are converted to 1-alkenes on oxidation to the selenoxide with Hydrogen Peroxide,25 Sodium Periodate,25 or t-Butyl Hydroperoxide,26 or by treatment with methyl fluorosulfonate and base-catalyzed elimination of the selenonium intermediate (eq 4).27

2-Hydroxyalkyl phenyl selenides, easily prepared from phenylselenomethyllithium and carbonyl compounds, are valuable precursors for the following.

Terminal Epoxides.10,13,28,29

Activation of the selenium moiety can be achieved by formation of selenonium salts (eq 5), oxidation to selenone (m-Chloroperbenzoic Acid, CH2Cl2, 20 °C)10 or treatment with thallium(I) ethoxide in chloroform, which produces a dichlorocarbene intermediate (eq 6)30

Terminal Alkenes.12

This reaction, which probably involves the intermediate formation of a seleniranium ion, is best achieved with Methanesulfonyl Chloride in the presence of Triethylamine6,12 or with p-Toluenesulfonic Acid (eq 7).31


Ketones, resulting from the rearrangement of the intermediate 2-hydroxyalkyl selenones, are obtained on reaction of 2-hydroxyalkyl selenides derived from aromatic ketones with m-CPBA (eq 8).10,28 Extension of this reaction to 1-phenyl-2-(phenylseleno)ethanol affords methyl phenylacetate in very good yield (86%) resulting from oxidation of the phenylacetaldehyde intermediate by the excess of m-CPBA used (3-5 equiv, MeOH, reflux, 3 h, eq 9).32

The processes reported above allow the synthesis of terminal epoxides and alkenes from a carbonyl compound in a way similar to that involving methylenesulfuranes and methylenetriphenylphosphorane. Phenylselenomethyllithium has the advantage that terminal epoxides and alkenes derived from hindered or enolizable carbonyl compounds, which are unavailable from ylides, can be prepared.1g

3-Hydroxyalkyl and 4-hydroxyalkyl phenyl selenides are available from phenylselenomethyllithium and terminal epoxides or oxetanes. They have been transformed to oxetanes (eq 2) and to tetrahydrofurans.4 The whole process allows the stepwise homologation of carbonyl compounds to epoxides, oxetanes, and tetrahydrofurans.4

Phenylselenomethyllithium is the first member of the series of a-selenoalkyllithiums. These can be prepared on reaction of butyllithiums with selenoacetals, which are readily available from carbonyl compounds and phenyl- or methylselenols. The reactions reported above can be advantageously extended to the higher homologs of selenides, but some further examples must be given (eqs 10-12).1a,1c,1e-i,33 The synthesis of the most strained or hindered alkenes is best achieved from methylseleno derivatives using Phosphorus(III) Iodide as reagent.1g,34 Methylseleno derivatives are also more appropriate for the synthesis of epoxides.1g,29,34 In such cases best results are obtained by using the two-step sequence involving the intermediate formation of b-hydroxyalkylselenonium salts. This allows the synthesis of the whole range of epoxides including those derived from a,b-unsaturated or hindered carbonyl compounds as well as those derived from selenoalkyllithiums bearing two alkyl groups on their carbanionic center. The latter compounds cannot be produced using the dichlorocarbene method since pinacol-type rearrangement leads instead to a ketone.35-38

Related Reagents.

Bis(phenylthio)methane; Dibromomethane-Zinc-Titanium(IV) Chloride; Methylenetriphenylphosphorane; Phenylthiomethyllithium.

1. (a) Krief, A. T 1980, 36, 2531. (b) Uemura, S.; Ohe, K. Yuki Gosei Kagaku Kyokaishi 1990, 48, 974 (CA 1991, 114, 121 580v). (c) Nicolaou, K. C.; Petasis, N. A. Selenium In Natural Products Synthesis; CIS: Philadephia, 1984; p 1. (d) Reich, H. J. Oxidation in Organic Chemistry; Academic: New York, 1978; Vol. 5, p 1. (e) Reich, H. J. Organoselenium Chemistry; Wiley: New York, 1987; p 243. (f) Krief, A. The Chemistry of Organic Selenium and Tellurium Compounds; Wiley: New York, 1987; Vol. 2, p 675. (g) Krief, A. COS 1991, 1, 629. (h) Krief, A. COS 1991, 3, 85. (i) Krief, A. Top. Curr. Chem. 1987, 135, 1.
2. Seebach, D.; Peleties, N. AG(E) 1969, 8, 450.
3. Seebach, D.; Peleties, N. CB 1972, 105, 511.
4. Sevrin, M.; Krief, A. TL 1980, 21, 585.
5. Reich, H. J. ACR 1979, 12, 22.
6. Reich, H. J.; Chow, F.; Shah, S. K. JACS 1979, 101, 6638.
7. Dumont, W.; Sevrin, M.; Krief, A. AG(E) 1977, 16, 541.
8. Krief, A.; Dumont, W.; Clarembeau, M.; Bernard, G.; Badaoui, E. T 1989, 45, 2005.
9. Krief, A.; Dumont, W.; Laboureur, J. L. TL 1988, 29, 3265.
10. Uemura, S.; Ohe, K.; Sugita, N. CC 1988, 111.
11. Labar, D.; Krief, A.; Norberg, B.; Evrard, G.; Durant, F. BSB 1985, 94, 1083.
12. Reich, H. J.; Chow, F. CC 1975, 790.
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14. Wartski, L.; El Bouz, M.; Seyden-Penne, J.; Dumont, W.; Krief, A. TL 1979, 1543.
15. Jarowicki, K.; Kocienski, P.; Marczak, S.; Willson, T. TL 1990, 31, 3433.
16. Willson, T.; Kocienski, P.; Faller, A.; Campbell, S. CC 1987, 106.
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18. Sevrin, M.; Van Ende, D.; Krief, A. TL 1976, 2643.
19. Clive, D. L. J.; Chittattu, G. J.; Farina, V.; Kiel, W. A.; Menchen, S. M.; Russell C. G.; Singh, A.; Wong, C. K.; Curtis, N. J. JACS 1980, 102, 4438.
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21. Uemura, S.; Fukuzawa, S.; Toshimitsu, A. CC 1983, 1501.
22. Uemura, S.; Fukuzawa, S. JCS(P1) 1985, 471.
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25. Sharpless, K. B.; Young, M. W. JOC 1975, 40, 947.
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27. Halazy, S.; Krief, A. TL 1979, 4233.
28. Uemura, S.; Ohe, K.; Sugita, N. J. Chem. Soc. Pakistan 1990, 1697.
29. Krief, A.; Dumont, W.; Van Ende, D.; Halazy, S.; Labar, D.; Laboureur, J-L.; Lê, T. Q. H 1989, 28, 1203.
30. Laboureur, J. L.; Dumont, W.; Krief, A. TL 1984, 25, 4569.
31. Remion, J.; Dumont, W.; Krief, A. TL 1976, 1385.
32. Uemura, S.; Ohe, K; Yamauchi, T.; Mizutaki, S.; Tamaki, K. JCS(P1) 1990, 907.
33. Calverley, M. J. TL 1987, 28, 1337.
34. Labar, D.; Krief, A. CC 1982, 564.
35. Krief, A.; Laboureur, J. L.; Dumont, W.; Labar, D. BSF(2) 1990, 681.
36. Schmit, C.; Sahraoui-Taleb, S.; Differding, E.; Dehasse-De Lombaert, C. G.; Ghosez, L. TL 1984, 25, 5043.
37. Fitjer, L.; Scheuermann, H-J.; Wehle, D. TL 1984, 25 2329.
38. Glover, J. R. Proceedings of the Symp. on Selenium-Tellurium Env., Ind. Health Found; Pittsburgh, PA, 1976.

Alain Krief

Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium

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