Lithium Di-n-propylcuprate1

n-Pr2CuLi

[43093-17-0]  · C6H14CuLi  · Lithium Di-n-propylcuprate  · (MW 156.69)

(propylating reagent; undergoes conjugate addition reactions,1a,b,e epoxide addition reactions,1a,e substitution reactions with alkyl and vinyl substrates,1a,c,e carbocupration with alkynes,1e and acylation reactions1e)

Physical Data: dark suspension in Et2O at 0 °C;2 brown-black solution in THF between -20 and -10 °C.3

Solubility: sol THF, Et2O.

Preparative Methods: prepared in situ from CuI salts (CuI or CuBr.SMe2) under N2 or argon atmosphere.4 Rate of cuprate formation is temperature- and CuI salt-dependent, and reagent prepared from CuI halides is critically dependent on the purity of the CuI salts used (see Lithium Dimethylcuprate for purification of CuI and CuBr).

Handling, Storage, and Precautions: stable in solution for several hours below -60 °C; cuprate reactions are generally carried out at -78 °C. Air- and moisture-sensitive; use in a fume hood.

Introduction.

Lithium di-n-propylcuprate displays the characteristic reactivity patterns of lithium diorganocuprates (see Lithium Di-n-butylcuprate, Lithium Dimethylcuprate, Lithium Diphenylcuprate).

Addition Reactions.

n-Pr2CuLi reacts with a,b-alkenyl ketones,1e,4,5 esters,1e,6,7,8 lactones,8 and 1,3-dioxin-4-ones (eq 1)2 with 1,4-transfer of the propyl ligand. n-Pr2CuLi undergoes 1,6-addition to dienyl amides9 and 1,8-addition to trienyl ketones and esters (eq 2).10 Conjugate addition to 2-alkynoic esters proceeds in an exclusively cis manner (eq 3).11

Substitution Reactions.

n-Pr2CuLi participates in substitution reactions with alkyl halides1a,e,12-14 and sulfonate esters.1a,e,12a,c,d,13,15-17 Several natural product syntheses employ this coupling methodology as the key step.12,13,15-17 Vinyl iodides (eq 4)11b afford good yields of substitution products with retention of configuration. 2-Trimethylsilylpentanoyl chloride1e and g-bromobutanoyl chloride react with n-Pr2CuLi to afford the corresponding propyl ketones.

a,b-Epoxysilanes (eq 5),18 alkenyl lactones,3 and alkynyl carboxylates1e participate in anti-SN2 pathways, although regio- and stereochemistry can vary.1 Reaction of a,b-unsaturated oxazolidines with n-Pr2CuLi (eq 6)19 also proceeds in an SN2 manner. The steric course can be reversed and the diastereoselectivity enhanced by salt and/or solvent effects.

Miscellaneous Reactions.

n-Pr2CuLi reacts with 9-Borabicyclo[3.3.1]nonane (9-BBN) to afford B-alkyl-9-BBN.20 This procedure can be extended to prepare mixed organoboranes.


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. Gmelin Handbook of Inorganic Chemistry; Springer: Berlin, 1983; Copper, Part 2.
2. Seebach, D.; Zimmermann, J.; Gysel, U.; Ziegler, R.; Ha, T.-K. JACS 1988, 110, 4763.
3. MacMillan, J.; Taylor, D. A. JCS(P1) 1985, 837.
4. Bertz, S. H.; Gibson, C. P.; Dabbagh, G. TL 1987, 28, 4251.
5. Takayanagi, H.; Nishino, C. J. Chem. Ecol. 1982, 8, 883.
6. Oppolzer, W.; Dudfield, P. HCA 1985, 68, 216.
7. Four, P.; Riviere, H.; Tang, P. W. TL 1977, 3879.
8. Bernardi, A.; Beretta, M. G.; Colombo, L.; Gennari, C.; Poli, G.; Scolastico, C. JOC 1985, 50, 4442.
9. Barbot, F.; Kadib-Elban, A.; Miginiac, Ph. TL 1983, 24, 5089.
10. Barbot, F.; Kadib-Elban, A.; Miginiac, Ph. JOM 1988, 345, 239.
11. (a) Bowlus, S. B.; Katzenellenbogen, J. A. TL 1973, 1277. (b) Bowlus, S. B.; Katzenellenbogen, J. A. JOC 1973, 38, 2733.
12. (a) Bernardini, A.; El Hallaoui, A.; Jacquier, R.; Pigiere, Ch.; Viallefont, Ph.; Bajgrowicz, J. TL 1983, 24, 3717. (b) Bajgrowicz, J. A.; El Hallaoui, A.; Jacquier, R.; Pigiere, C.; Viallefont, Ph. TL 1984, 25, 2231. (c) Bajgrowicz, J. A.; El Hallaoui, A.; Jacquier, R.; Pigiere, Ch.; Viallefont, Ph. TL 1984, 25, 2759. (d) Bajgrowicz, J. A.; El Hallaoui, A.; Jacquier, R.; Pigiere, Ch.; Viallefont, Ph. T 1985, 41, 1833.
13. Wistrand, L.-G.; Skrinjar, M. T 1991, 47, 573.
14. Larcheveque, M.; Petit, Y. TL 1984, 25, 3705.
15. Saliou, C.; Fleurant, A.; Celerier, J. P.; Lhommet, G. TL 1991, 32, 3365.
16. Yu, H.-M.; Becker, H.; Mangold, H. K. CI(L) 1989, 39.
17. Jain, S. C.; Dussourd, D. E.; Conner, W. E.; Eisner, T.; Guerrero, A.; Meinwald, J. E. JOC 1983, 48, 2266.
18. Hudrlik, P. F.; Peterson, D.; Rona, R. J. JOC 1975, 40, 2263.
19. Berlan, J.; Besace, Y.; Pourcelot, G.; Cresson, P. T 1986, 42, 4757.
20. Whiteley, C. G. S. Afr. J. Chem. 1982, 35, 9.

Janice W. Dieter & R. Karl Dieter

Clemson University, SC, USA



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