Lithium Cyclopropyl(phenylthio)cuprate1

[84180-46-1]  · C9H10CuLiS  · Lithium Cyclopropyl(phenylthio)cuprate  · (MW 220.72)

(heterocuprate useful in 1,4-addition-elimination reactions2 and annulations3)

Solubility: sol THF; less sol ether.

Analysis of Reagent Purity: an assay to determine relative thermal stabilities4 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 cyclopropyl phenyl ketone is measured by GC, the response of which is calibrated using authentic product and n-dodecane as internal standard.

Preparative Method: cyclopropyllithium5,6 is prepared by cooling a 0.25 M THF solution of bromocyclopropane under Ar to -78 °C; dropwise addition of 1.0 equiv of a solution of s-Butyllithium is followed by stirring for 2 h; this cyclopropyllithium solution is transferred by cannula to a stirred, -78 °C THF slurry of Phenylthiocopper(I)7 under Ar; the resultant mixture is warmed to -20 °C; a clear, light brown solution of cuprate forms after stirring for 20 min; it is cooled to -78 °C and is used directly.8

Handling, Storage, and Precautions: best results are obtained with PhSCu prepared from high purity CuI salts,9 dry, O2-free solvents, and alkyllithium solutions free of contaminating alkoxides or hydroxides;10 s-BuLi is pyrophoric;11 care must be exercised in its handling, and a fume hood should be used; the reagent is more stable than lithium dicyclopropylcuprate, which decomposes upon prolonged standing at -78 °C.5

This cyclopropyl organometal reagent is representative of the heterocuprate class of organocopper reagents.12 The cyclopropyl group is nucleophilically reactive, whereas the SPh group is not. The nontransferable SPh group, or dummy ligand,13 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 higher reaction temperatures are required, or when the organolithium used to form the cuprate is difficult or expensive to prepare.

Lithium cyclopropyl(phenylthio)cuprate has been used in 1,4-addition-elimination reactions with a-oxoketene dithioacetals14 and 3-halo-2-alkenones.8,15 The latter substrates yield 3-cyclopropyl-2-alkenones which undergo high-yield thermal ring expansions, providing a two-step, five-membered ring annulation method.8 Bicyclo[4.3.0]-1-nonen-2-ones (eq 1) and bicyclo[3.3.0]-1-octen-2-ones of use in the synthesis of zizaene-type sesquiterpenoids can be prepared.8 Spiro[4.5]-1-decen-6-ones and spiro[4.4]-1-nonen-6-ones, which provide access to vetivane-type sesquiterpenoids, also can be prepared.15

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. Piers, E.; Morton, H. E.; Nagakura, I.; Thies, R. W. CJC 1983, 61, 1226.
4. Bertz, S. H.; Dabbagh, G. CC 1982, 1030.
5. Marino, J. P.; Browne, L. J. JOC 1976, 41, 3629.
6. Alternative preparations include Br-Li exchange in ether5 using t-BuLi and direct lithiation: (a) Seyferth, D.; Cohen, H. M. JOM 1963, 1, 15. (b) Gilman, H.; Cartledge, F. K. JOM 1964, 2, 447.
7. PhSCu in purities of 95->98% is commercially available. For preparation of PhSCu in THF, see Corey, E. J.; Boger, D. L. TL 1978, 39, 4597.
8. Piers, E.; Banville, J.; Lau, C. K.; Nagakura, I. CJC 1982, 60, 2965.
9. 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.
10. Corey, E. J.; Naef, R.; Hannon, F. J. JACS 1986, 108, 7114.
11. Wakefield, B. J. Organolithium Methods; Academic: New York, 1988; pp 11-15.
12. Posner, G. H.; Whitten, C. E.; Sterling, J. J. JACS 1973, 95, 7788.
13. Lipshutz, B. H. SL 1990, 119.
14. Dieter, R. K.; Silks, L. A., III; Fishpaugh, J. R.; Kastner, M. E. JACS 1985, 107, 4679.
15. Piers, E.; Lau, C. K.; Nagakura, I. CJC 1983, 61, 288.

Martin Hulce

Creighton University, Omaha, NE, USA

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