Lithium Methyl(phenylthio)cuprate1


[56831-21-1]  · C7H8CuLiS  · Lithium Methyl(phenylthio)cuprate  · (MW 194.71)

(heterocuprate, useful in 1,4-additions,2 carbocuprations,3 and substitutions4)

Solubility: sol ether, THF.

Analysis of Reagent Purity: an assay to determine relative thermal stabilities5 can be used to estimate reagent quality and concentration: a sample of known volume and temperature is quenched with excess PhCOCl; the yield of acetophenone is measured by GC, after calibration using authentic product and n-dodecane as internal standard.

Preparative Method: from Phenylthiocopper(I) prepared in situ: 1.0 equiv of n-Butyllithium is added dropwise to a 0.2 M, 0 °C THF solution of Thiophenol in a three-neck flask equipped with N2 inlet, solid addition funnel, and rubber septum. After stirring for 10 min, 1.0 equiv of Copper(I) Iodide is added via the addition funnel. Stirring for an additional 15 min provides a clear, yellow solution, to which 1.0 equiv of a solution of Methyllithium is added dropwise via syringe. After 15 min, the brown solution is ready for use.6 Alternate sources of PhSCu may be acceptable.7

Handling, Storage, and Precautions: best results are obtained with high purity CuI salts,8 dry, O2-free solvents, and methyllithium solutions free of contaminating alkoxides or hydroxides.9 MeLi is pyrophoric;10 due care must be exercised in its handling. Thermal decomposition of the reagent is minimal at or below room temperature.11 Use in a fume hood.

Lithium methyl(phenylthio)cuprate is representative of the heterocuprate class of organocopper reagents.6 The Me group is nucleophilically reactive, whereas the SPh group is not. These nontransferable groups are called dummy ligands;12 the SPh group in particular provides enhanced thermal stability and solubility compared to the analogous homocuprate. Heterocuprates generally exhibit less nucleophilic reactivity than corresponding homocuprates; however, increased thermal stabilities coupled with greater efficiency in use of the transferable ligand make them reasonable alternative reagents. This is particularly true when relatively high reaction temperatures are required, when the organolithium used to form the cuprate is difficult or expensive to prepare, or when overalkylation using the homocuprate is observed.

The reagent has been used in nucleophilic substitution reactions of allylic acetates13 and 9-BBN,14 as well as in conjugate additions to a-oxoketene dithioacetals15 and a,b-unsaturated oxazolidines16 and ketones.17 Good results have been reported in carbocupration reactions using alkynes (eq 1)18 and cyclopropenes;19 the analogous lithium methyl(methylthio)cuprate is used to synthesize tertiary thiols from dithio esters.20 On the other hand, cross coupling with organomercury reagents is unsatisfactory.11 Preferential transfer of the phenylthio group21 has been observed; this behavior is substrate dependent and should not normally be anticipated.

Related Reagents.

Lithium t-Butoxy(t-butyl)cuprate; Lithium n-Butyl(phenylthio)cuprate; Lithium Cyclopropyl(phenylthio)cuprate; Lithium (3,3-Diethoxy-1-propen-2-yl)(phenylthio)cuprate; Lithium Methyl(phenylseleno)cuprate.

1. (a) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (b) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents; Wiley: New York, 1980.
2. (a) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon: New York, 1992. (b) Kozlowski, J. A. COS 1991, 4, 169. (c) Hulce, M.; Chapdelaine, M. J. COS 1991, 4, 237. (d) Chapdelaine, M. J.; Hulce, M. OR 1990, 38, 225. (e) Taylor, R. J. K. S 1985, 364. (f) Posner, G. H. OR 1972, 19, 1.
3. Knochel, P. COS 1991, 4, 865.
4. Posner, G. H. OR 1975, 22, 253.
5. Bertz, S. H.; Dabbagh, G. CC 1982, 1030.
6. Posner, G. H.; Whitten, C. E.; Sterling, J. J. JACS 1973, 95, 7788.
7. PhSCu in purities of 95 to >98% is commercially available. For the preparation of PhSCu in THF, see Corey, E. J.; Boger, D. L. TL 1978, 39, 4597.
8. Purification methods: (a) Posner, G. H.; Sterling, J. J. JACS 1973, 95, 3076. (b) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 322. (c) Lipshutz, B. H.; Whitney, S.; Kozlowski, J. A.; Breneman, C. M. TL 1986, 27, 4273.
9. Corey, E. J.; Naef, R; Hannon, F. J. JACS 1986, 108, 7114.
10. Wakefield, B. J. Organolithium Methods; Academic: New York, 1988; pp 11-15.
11. Larock, R. C.; Leach, D. R. OM 1982, 1, 74.
12. Lipshutz, B. H. SL 1990, 119.
13. Levisalles, J.; Rudler-Chauvin, M.; Rudler, H. JOM 1977, 136, 103.
14. Whitely, C. G.; Zwane, I. JOC, 1985, 50, 1969.
15. (a) Dieter, R. K.; Silks, L. A., III; Fishpaugh, J. R.; Kastner, M. E. JACS 1985, 107, 4679. (b) Dieter, R. K.; Fishpaugh, J. R. JOC 1983, 48, 4439.
16. Berlan, J.; Besace, Y.; Prat, D.; Pourcelot, G. JOM 1984, 264, 399.
17. (a) Piers, E.; Cheng, K. F.; Nagakura, I. CJC 1982, 60, 1256. (b) Hannah, D. J.; Smith, R. A. J.; Teoh, I.; Weavers, R. T. AJC 1981, 34, 181.
18. Alexakis, A.; Commerçon, A.; Coulentianos, C.; Normant, J. F. T 1984, 40, 715.
19. Nakamura, E.; Isaka, M.; Matsuzawa, S. JACS 1988, 110, 1297.
20. Bertz, S. H.; Dabbagh, G.; Williams, L. M. JOC 1985, 50, 4415.
21. (a) Back, T. G.; Collins, S.; Krishna, M. V.; Law, K.-W. JOC 1987, 52, 4258. (b) Pearson, A. J. AJC 1977, 30, 345.

Martin Hulce

Creighton University, Omaha, NE, USA

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