Lithium Dimethylcuprate-Boron Trifluoride1


[15681-48-8]  · C2H6CuLi  · Lithium Dimethylcuprate-Boron Trifluoride  · (MW 100.57) (BF3)

[7637-07-2]  · BF3  · Lithium Dimethylcuprate-Boron Trifluoride  · (MW 67.81) (BF3.Et2O)

[109-63-7]  · C4H10BF3O  · Lithium Dimethylcuprate-Boron Trifluoride  · (MW 141.95)

(methylating reagent that undergoes accelerated conjugate addition reactions,1 1,2-addition reactions,2 substitution reactions with alkyl1,3 and allylic substrates,1,4 and reduction reactions4)

Physical Data: clear solution in THF; 1H NMR data for Me2CuLi + 2 BF3.Et2O at -80 °C is suggestive of a four-component system: Me2CuLi (d -1.57 ppm) + Me3Cu2Li (d -1.31 and -0.35 ppm) + MeLi.BF3 (d 0.16 ppm) + BF3.1b

Solubility: sol THF, Et2O

Preparative Methods: addition of 2 equiv of Boron Trifluoride Etherate to Lithium Dimethylcuprate prepared from CuI salts and Methyllithium at -78 °C gives a clear solution in THF; warming the solution from -78 to -60 °C over 10 min generates a solution of Me3Cu2Li + BF3 + MeLi.BF3.1b The reagent can also be prepared by addition of Boron Trifluoride to Me2CuLi, although use of BF3.Et2O is more convenient and affords identical results.3b

Handling, Storage, and Precautions: air- and moisture-sensitive; handle under inert atmosphere in a fume hood.

Addition Reactions.

Addition of BF3.Et2O to solutions of Me2CuLi affords a reagent and reaction conditions in which conjugate transfer of the methyl ligand to a,b-alkenyl ketones (eq 15b),5 enoates,6 lactones5b,7 and alkylidenemalonates6a,8 is accelerated relative to Me2CuLi. The reagents MeCu.BF3 and Me2Cu(CN)Li2/BF3 can also be used, and the relative effectiveness of each reagent is generally substrate dependent. g-Silyloxy- (eq 2)6a and g-amino-a,b-enoates6b as well as g-alkoxyalkylidenemalonates6a undergo conjugate addition reactions with these reagents with varying degrees of stereoselectivity and yield. The reagent has often been used on substrates with reduced reactivity resulting from substitution and steric factors. This reagent combination has been effectively used in a homoconjugate addition reaction with a cyclopropyl ketone (eq 3).9

1,2-Addition of Me2CuLi/BF3.Et2O to chiral imines provides a synthetic route to chiral amines that is stereodivergent relative to the 1,2-addition reactions of organolithium and organocerium reagents (eq 4).2

Substitution Reactions.

Addition of BF3.Et2O to solutions of Me2CuLi provides a reagent and reaction conditions that can effect substitution reactions on substrates, such as aziridines (eq 5)10 and acetals,3 that are normally unreactive toward Me2CuLi alone. Although Titanium(IV) Chloride can also be employed, superior yields are generally obtained with BF3.Et2O (eq 6).3b A b-bromobutenolide undergoes a substitution reaction with varying combinations of Me2CuLi, MeLi, and BF3.Et2O (eq 7).11

Allylic acetals12 and oxazolidines13 undergo reaction with Me2CuLi/BF3 to afford mixtures of rearranged (SN2) and unrearranged (SN2) substitution products, while allylic acetals12 afford, exclusively, substitution products via SN2 pathways. Chiral allylic oxazolidines give substitution products with very modest asymmetric induction.13 Good asymmetric induction has been achieved with chiral g-sulfonyloxy-a,b-enoates, which undergo preferential allylic substitution (eq 8).4

Reduction Reactions.

g-Acyloxy-a,b-enoates4 undergo reduction upon treatment with Me2CuLi/BF3, in contrast to the g-alkoxy derivatives,6a which undergo conjugate addition, and the g-mesyloxy derivatives,4 which undergo allylic substitution. BF3.Et2O as an additive attenuates the electron transfer properties of Me2CuLi.14

Related Reagents.

Lithium Cyano(methyl)cuprate; Lithium Dimethylcuprate; Methylcopper; Methylcopper-Boron Trifluoride Etherate.

1. (a) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (b) Lipshutz, B. H.; Ellsworth, E. L.; Siahaan, T. J. JACS 1989, 111, 1351.
2. Ukaji, Y.; Watai, T.; Sumi, T.; Fujisawa, T. CL 1991, 1555.
3. (a) Normant, J. F.; Alexakis, A.; Ghribi, A.; Mangeney, P. T 1989, 45, 507. (b) Ghribi, A.; Alexakis, A.; Normant, J. F. TL 1984, 25, 3083.
4. Ibuka, T.; Nakao, T.; Nishii, S.; Yamamoto, Y. JACS 1986, 108, 7420.
5. (a) Smith, A. B., III; Jerris, P. J. JOC 1982, 47, 1845. (b) Still, W. C.; Galynker, I. T 1981, 37, 3981. (c) Mehta, G.; Murthy, A. N.; Reddy, D. S.; Reddy, A. V. JACS 1986, 108, 3443. (d) Banik, B. K.; Chakraborti, A. K.; Ghatak, U. R. JCR(S) 1986, 406. (e) Banik, B. K.; Ghosh, S.; Ghatak, U. R. T 1988, 44, 6947. (f) Cha, J. K.; Lewis, S. C. TL 1984, 25, 5263.
6. (a) Yamamoto, Y.; Chounan, Y.; Nishii, S.; Ibuka, T.; Kitahara, H. JACS 1992, 114, 7652. (b) Reetz, M. T.; Röhrig, D. AG(E) 1989, 28, 1706.
7. Still, W. C.; Galynker, I. JACS 1982, 104, 1774.
8. Ibuka, T.; Aoyagi, T.; Yamamoto, Y. CPB 1986, 34, 2417.
9. Adams, J.; Belley, M. TL 1986, 27, 2075.
10. Eis, M. J.; Ganem, B. TL 1985, 26, 1153.
11. Olsen, R. K.; Hennen, W. J.; Wardle, R. B. JOC 1982, 47, 4605.
12. Ghribi, A.; Alexakis, A.; Normant, J. F. TL 1984, 25, 3079.
13. Berlan, J.; Besace, Y.; Prat, D.; Pourcelot, G. JOM 1984, 264, 399.
14. Smith, R. A. J.; Vellekoop, A. S. T 1989, 45, 517.

R. Karl Dieter

Clemson University, SC, USA

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