Lithium n-Butyl(phenylthio)cuprate1


[53128-68-0]  · C10H14CuLiS  · Lithium n-Butyl(phenylthio)cuprate  · (MW 236.80)

(primary heterocuprate capable of nucleophilic additions and substitutions2)

Solubility: sol THF, ether.

Analysis of Reagent Purity: an assay to determine relative thermal stabilities3 can be used to estimate reagent quality and concentration: a sample of known volume and temperature is quenched with excess PhCOCl, and the yield of PhCO(n-Bu) is measured by GC, the response of which is calibrated using authentic product and n-dodecane as internal standard.

Preparative Methods: 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 which is cooled to -78 °C; 1.0 equiv of n-BuLi is then added dropwise via syringe;4,5 after 1 h, the light brown, opaque solution is ready for use. Alternate sources of PhSCu may be acceptable; PhSCu in purities of 95->98% is commercially available.6

Handling, Storage, and Precautions: use in a fume hood; best results are obtained with high-purity copper(I) salts,7 dry, O2-free solvents, and alkyllithium solutions free of contaminating alkoxides or hydroxides;8 n-BuLi is pyrophoric,9 and due care must be exercised in its handling; the reagent has greater stability in THF than in ether; thermal decomposition is minimal at or below -25 °C but is substantial at 0 °C.3b

This primary alkyl organometal reagent is representative of the heterocuprate class of organocopper reagents.10 The n-Bu group is nucleophilically reactive, whereas the SPh group is not. Such nontransferable groups are called dummy ligands;11 the SPh dummy ligand in particular provides enhanced thermal stability and solubility compared with the analogous homocuprate. Heterocuprates generally exhibit less nucleophilic reactivity than the 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, or when the organolithium used to form the cuprate is difficult or expensive to prepare.

Lithium n-butyl(phenylthio)cuprate has been used in nucleophilic substitution reactions of arenesulfonyl fluorides,12 allylic acetates,13 9-BBN,14 propargylic carbamates,15 and bromoalkenes,16 as well as in nucleophilic additions to acetoxyepoxides.17 It is a good choice for 1,4-addition of an n-Bu group, having been used in 1,4-addition-elimination reactions of a-oxoketene dithioacetals4 and 3-halo-2-cycloalkenones,18 and in tandem vicinal dialkylation reactions of 5-methyleneoxazolones19 and alkynes.20 A typical example is the use of the reagent in the stereospecific synthesis of (Z)-2-heptenoic acid from acetylene (eq 1).20a

Related Reagents.

For related heterocuprates, see Lithium Methyl(phenylthio)cuprate; for discussion of lithium dialkylcuprates, see Lithium Dimethylcuprate.

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) Posner, G. H. OR 1975, 22, 253. (f) Posner, G. H. OR 1972, 19, 1.
3. (a) Bertz, S. H.; Dabbagh, G. CC 1982, 1030. (b) Bertz, S. H.; Dabbagh, G.; Villacorta, G. M. JACS 1982, 104, 5824.
4. Dieter, R. K.; Silks, L. A., III; Fishpaugh, J. R.; Kastner, M. E. JACS 1985, 107, 4679.
5. (a) Posner, G. H.; Brunelle, D. J.; Sinoway, L. S 1974, 662. (b) For a detailed preparation of the corresponding t-Bu heterocuprate, see Posner, G. H.; Whitten, C. E. OSC 1988, 6, 248.
6. Corey, E. J.; Boger, D. L. TL 1978, 39, 4597.
7. 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.
8. Corey, E. J.; Naef, R.; Hannon, F. J. JACS 1986, 108, 7114.
9. Wakefield, B. J. Organolithium Methods; Academic: New York, 1988; pp 11-15.
10. Posner, G. H.; Whitten, C. E.; Sterling, J. J. JACS 1973, 95, 7788.
11. Lipshutz, B. H. SL 1990, 119.
12. Frye, L. L.; Sullivan, E. L.; Cusack, K. P.; Funaro, J. M. JOC 1992, 57, 697.
13. Kal'yan, Yu. B.; Krimer, M. Z.; Smit, V. A.; Moiseenkov, A. M.; Lutsenko, A. I. IZV 1985, 2092 (CA 1986, 105, 97 193n).
14. Whiteley, C. G.; Zwane, I. JOC 1985, 50, 1969.
15. Pirkle, W. H.; Boeder, C. W. JOC 1978, 43, 1950.
16. Miller, R. B.; McGarvey, G. JOC 1979, 44, 4623.
17. Amos, R. A.; Katzenellenbogen, J. A. JOC 1977, 42, 2537.
18. (a) Piers, E.; Cheng, K. F.; Nagakura, I. CJC 1982, 60, 1256. (b) Christie, R. M.; Gill, M.; Rickards, R. W. JCS(P1) 1981, 593.
19. Schulz, G.; Gruber, P.; Steglich, W. CB 1979, 119, 3221.
20. (a) Alexakis, A.; Normant, J.; Villiéras, J. TL 1976, 3461. (b) Furber, M.; Taylor, R. J. K.; Burford, S. C. TL 1985, 26, 2731.

Martin Hulce

Creighton University, Omaha, NE, USA

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