Lithium Di-n-butylcuprate1


[24406-16-4]  · C8H18CuLi  · Lithium Di-n-butylcuprate  · (MW 184.75)

(butylating reagent; undergoes conjugate addition reactions,1a,b,e,f 1,2-addition reactions,1e,2 substitution reactions with alkyl, vinyl, aryl, and allylic substrates,1a,c,e reduction of carbon-heteroatom bonds,3 oxidative dimerization,4a and oxidative coupling with amines4b)

Physical Data: 1H NMR (Et2O) d -6.99 to -7.14 ppm (t, J = 7.0 Hz, 2 H, -60 to +20 °C); (C5H12) d -7.29 to -7.32 ppm (-50 to +35 °C).5

Solubility: sol THF, Et2O.

Preparative Methods: prepared in situ from CuI salts under N2 or argon atmosphere.1a Rate of cuprate formation is temperature- and CuI salt-dependent; reagent prepared from CuI halides may contain free BuLi.6a Dark-colored solutions are indicative of decomposition (see Lithium Dimethylcuprate for purification of CuI and CuBr). Colorless solutions of Bu2CuLi can be prepared from BuCu obtained by low-temperature centrifugation.1b Polymer-bound n-Bu2CuLi can be prepared.7

Handling, Storage, and Precautions: stable in solution for several hours below 0 °C (10% decomposition at 0 °C for 30 min)6b and is very sensitive to O2. Use in a fume hood.

Addition Reactions.

Reaction of Bu2CuLi with a,b-alkenyl ketones (eq 1),1,8 aldehydes,9 esters,1 lactones,1 sulfoxides,10a sulfones,10b sulfoximines,10c N-tosylamides,11a nitriles,11b N-nitroso11c and nitro11d compounds, phosphonates,12a phosphine oxides,12b phosphinates,1a and phosphonium salts (eq 2)12c results in conjugate addition of the butyl ligand; ligand transfer can be facilitated by bis-activation1,13 of the alkene (e.g. alkylidene malonates). Bis-activated cyclopropanes1d afford products of homoconjugate addition, and dienyl systems14,15 generally yield 1,6-addition products. Byproducts consistent with an equilibrium presence of n-BuLi6a are sometimes observed.15 The reagent is compatible with transition metal carbonyls (eq 1)8 and nitroalkanes16 under appropriate conditions.

Exploitation of the anion resulting from conjugate addition17 provides for powerful synthetic opportunities (eq 2).12c b-Nucleofuge-substituted a,b-unsaturated systems undergo substitution with varying degrees of stereoselectivity (eq 3).18 Procedures for achieving absolute asymmetric conjugate addition of Bu2CuLi are available.19

Although Bu2CuLi effects carbocupration of alkynes more readily than Me2CuLi, copper-catalyzed Grignard additions are more efficient and widely employed.1a

Addition of Chlorotrimethylsilane facilitates 1,2-addition of Bu2CuLi to ketones2 and to aldehydes with increased Cram selectivity,2,20a while addition of crown ethers favors formation of anti-Cram20b products. 1,2-Addition of Bu2CuLi to N-silylformamides affords imines.20c

Substitution Reactions.

Bu2CuLi participates in substitution reactions with alkyl (e.g. halides (eq 4),21 carboxylates, sulfonate esters) and alkenyl substrates (e.g. enol triflates and phosphates); the reaction is very general.1a,c Substitution reactions occur with b-lactones22 and often proceed with good regio- and stereocontrol with oxiranes1 (eq 5)23 and tosylated aziridines.24 Acylation of Bu2CuLi with thiol esters provides a good route to ketones.25

Although the preference of allylic substrates (e.g. halides, sulfonimides, carboxylates, oxiranes, sulfones, carbamates, and nitro compounds26) for anti-SN2 pathways is synthetically useful, steric effects, leaving groups, and substrate structure can alter regiochemistry and stereochemical integrity can be lost by isomerization pathways.27 Propargyl substrates generally give substitution with rearrangement (eq 6).28

Miscellaneous Reactions.

Bu2CuLi will reduce a variety of carbon-heteroatom bonds, and the reaction can be exploited synthetically.1a,d Reduction of cyclopropyl halides gives an intermediate copper species that can be alkylated or acylated (eq 7)3 with some stereocontrol. Oxidative dimerization4a of Bu2CuLi affords octane; an oxidative coupling reaction can be used to prepare butylated amines (eq 8).4b

Related Reagents.

Lithium Diethylcuprate; Lithium Dimethylcuprate; Lithium Diphenylcuprate; Lithium Di-n-propylcuprate.

1. (a) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (b) Posner, G. H. OR 1972, 19, 1. (c) Posner, G. H. OR 1975, 22, 253. (d) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents; Wiley: New York, 1980. (e) Faust, J.; Froböse, R. In Gmelin Handbook of Inorganic Chemistry; Springer: Berlin, 1983; Copper, Part 2. (f) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon: Oxford, 1992.
2. Matsuzawa, S.; Isaka, M.; Nakamura, E.; Kuwajima, I. TL 1989, 30, 1975.
3. Kitatani, K.; Hiyama, T.; Nozaki, H. BCJ 1977, 50, 1600.
4. (a) Whitesides, G. M.; San Filippo, J. Jr.; Casey, C. P.; Panek, E. J. JACS 1967, 89, 5302. (b) Yamamoto, H.; Maruoka, K. JOC 1980, 45, 2739.
5. San Filippo, J. Jr. IC 1978, 17, 275.
6. (a) Bertz, S. H.; Gibson, C. P.; Dabbagh, G. TL 1987, 28, 4251. (b) Bertz, S. H.; Dabbagh, G. CC 1982, 1030.
7. Schwartz, R. H.; San Filippo, J. Jr. JOC 1979, 44, 2705.
8. Uemura, M.; Oda, H.; Minami, T.; Hayashi, Y. TL 1991, 32, 4565.
9. (a) Chuit, C.; Foulon, J. P.; Normant, J. F. T 1980, 36, 2305. (b) Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.; Kuwajima, I. TL 1986, 27, 4029.
10. (a) Sugihara, H.; Tanikaga, R.; Tanaka, K.; Kaji, A. BCJ 1978, 51, 655. (b) Simpkins, N. S. T 1990, 46, 6951. (c) Pyne, S. G. JOC 1986, 51, 81.
11. (a) Nagashima, H.; Ozaki, N.; Washiyama, M.; Itoh, K. TL 1985, 26, 657. (b) Fang, J.-M.; Chang, H.-T. JCS(P1) 1988, 1945. (c) Kupper, R.; Michejda, C. J. JOC 1980, 45, 2919. (d) Bowlus, S. B. TL 1975, 3591.
12. (a) Bodalski, R.; Michalski, T. J.; Monkiewicz, J. PS 1980, 9, 121. (b) Pietrusiewicz, K. M.; Zablocka, M.; Monkiewicz, J. JOC 1984, 49, 1522. (c) Just, G.; O'Connor, B. TL 1985, 26, 1799.
13. Yamamoto, Y.; Nishii, S.; Ibuka, T. CC 1987, 1572.
14. Corey, E. J.; Chen, R. H. K. TL 1973, 1611.
15. Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Ishihara, Y.; Maruyama, K. JOC 1982, 47, 119.
16. Tamura, R.; Tamai, S.; Katayama, H.; Suzuki, H. TL 1989, 30, 3685.
17. (a) Taylor, R. J. K. S 1985, 364. (b) Chapdelaine, M. J.; Hulce, M. OR 1990, 38, 225.
18. Dieter, R. K.; Silks, L. A., III JOC 1986, 51, 4687.
19. Rossiter, B. E.; Swingle, N. M. CRV 1992, 92, 771.
20. (a) Arai, M.; Nemoto, T.; Ohashi, Y.; Nakamura, E. SL 1992, 309. (b) Yamamoto, Y.; Maruyama, K. JACS 1985, 107, 6411. (c) Feringa, B. L.; Jansen, J. F. G. A. S 1988, 184.
21. Barluenga, J.; Llavona, L.; Yus, M.; Concellon, J. M. JCS(P1) 1991, 2890.
22. Kawashima, M.; Sato, T.; Fujisawa, T. T 1989, 45, 403.
23. Shimizu, N.; Imazu, S.; Shibata, F.; Tsuno, Y. BCJ 1991, 64, 1122.
24. Tanner, D.; Birgersson, C.; Dhaliwal, H. K. TL 1990, 31, 1903.
25. Kim, S.; Lee, J. I. JOC 1983, 48, 2608.
26. Ono, N.; Hamamoto, I.; Kaji, A. CC 1984, 274.
27. Underiner, T. L.; Paisley, S. D.; Schmitter, J.; Lesheski, L.; Goering, H. L. JOC 1989, 54, 2369.
28. Yoneda, R.; Inagaki, N.; Harusawa, S.; Kurihara, T. CPB 1992, 40, 21.

R. Karl Dieter

Clemson University, SC, USA

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