Lithium Diethylamide


[816-43-3]  · C4H10LiN  · Lithium Diethylamide  · (MW 79.09)

(strong base; nitrogen nucleophile)

Physical Data: pKa = 31.7.1

Solubility: sol THF, Et2O, Et2O-hexane mixtures, Et2O-benzene mixtures; insol hydrocarbon solvents.

Form Supplied in: white solid.

Preparative Methods: by treating diethylamine with Phenyllithium or n-Butyllithium or, alternatively, by treating diethylamine with Lithium metal in the presence of Hexamethylphosphoric Triamide2 or an electron acceptor.3

Handling, Storage, and Precautions: reacts with water vigorously and ignites spontaneously in air. When heated to decomposition, it emits toxic fumes of NOx. Should be kept and handled under argon. Use in a fume hood.

Lithium Diethylamide as Base.

Lithium diethylamide is a strong base whose use may be complementary to Lithium Diisopropylamide. For example, LiNEt2 serves to abstract the o-proton of sorbic acid to generate a lithium trienolate which undergoes regioselective condensation with aldehydes and ketones (eq 1),4 and to prepare carbocyclic nitriles by a sequential inter- and intramolecular alkylation route (eq 2).5 LiNEt2 has been employed with a sterically hindered lactam for an a-deprotonation-cyclization reaction as part of the synthesis of (-)-d-N-normethylskytanthine, an alkaloid from Tecoma arequipensis (eq 3).6 LiNEt2 may be a superior base to LDA for enolate formation.7

Lithium diethylamide is widely used for base-induced epoxide opening to allylic alcohols and rearrangement via carbenoids.8 Two reaction pathways are observed: b-syn-elimination8c to afford an allylic alcohol (eq 4) and a-elimination to generate a carbenoid followed by C-H insertion (eqs 5 and 6). Allylic deprotonation followed by intramolecular epoxide ring opening has been observed (eq 6). The b-elimination process is often highly stereoselective and therefore has synthetic value.8h

LiNEt2 is sufficiently basic to effect a-deprotonation of allenic ethers. Subsequent reaction with ketones followed by acid treatment affords 3-furanones (eq 7).9

Treatment of tetraphenylphosphonium bromide with LiNEt2 leads to 9-phenyldibenzophosphole10 which may be further transformed into Wittig-Horner reagents (eq 8), useful for highly stereoselective synthesis of alkenes.

Lithium Diethylamide as Nucleophile.

Treatment of aldehydes with a LiNEt2-Titanium Tetraisopropoxide complex generates a-amino alkoxides which undergo reaction with Grignard reagents to afford tertiary amines (eq 9).11 LiNEt2 attacks THP ethers of 2,4-alkadien-1-ols regioselectively at C-5 to furnish amino dienes with predominately (E,E) stereochemistry (eq 10).12 Treatment of perfluorinated alkanes with LiNEt2 results in b-elimination to provide terminal alkenes (eq 11).13 Further treatment with LiNEt2 leads to addition and fluoride elimination to give enamines which, after hydrolysis, produce perfluorinated amides. Similarly, chloroalkynes lead to ynamines (eq 12).14

Related Reagents.

Lithium Diisopropylamide; Lithium Hexamethyldisilazide; Lithium Piperidide; Lithium Pyrrolidide; Lithium 2,2,6,6-Tetramethylpiperidide.

1. Ahlbrecht, H.; Schneider, G. T 1986, 42, 4729.
2. Normant, H.; Cuvigny, T.; Reisdorf, D. CR(C) 1969, 268, 521.
3. Gaudemar-Bardone, F.; Gaudemar, M. S 1979, 463.
4. Ballester, P.; Costa, A.; Garcia-Raso, A.; Gomez-Solivellas, A.; Mestres, R. TL 1985, 26, 3625.
5. Larcheveque, M.; Mulot, P.; Cuvigny, T. JOM 1973, 57, C33.
6. Cid, M. M.; Eggnauer, U.; Weber, H. P.; Pombo-Villar, E. TL 1991, 32, 7233.
7. Seebach, D.; Wasmuth, D. AG(E) 1981, 20, 971.
8. (a) Crandall, J. K.; Chang, L.-H. JOC 1967, 32, 435. (b) Rickborn, B.; Thummel, R. P. JOC 1969, 34, 3583. (c) Thummel, R. P.; Rickborn, B. JACS 1970, 92, 2064. (d) Thummel, R. P.; Rickborn, B. JOC 1972, 37, 3919. (e) McDonald, R. N.; Steppel, R. N.; Cousins, R. C. JOC 1975, 40, 1694. (f) Apparu, M.; Barrelle, M. TL 1976, 2837. (g) Williams, D. R.; Grote, J. JOC 1983, 48, 134. (h) Nemoto, H.; Morizumi, M.; Nagai, M.; Fukumoto, K.; Kametani, T. JCS(P1) 1988, 885.
9. Carlson, R. M.; Jones, R. W.; Hatcher, A. S. TL 1975, 1741.
10. (a) Hoffmann, H. CB 1962, 95, 2563. (b) Cornforth, J.; Cornforth, R. H.; Gray, R. T. JCS(P1) 1982, 2289. (c) Roberts, T. G.; Whitham, G. H. JCS(P1) 1985, 1953. (d) Elliott, J.; Warren, S. TL 1986, 27, 645. (e) Vedejs, E.; Marth, C. TL 1987, 28, 3445.
11. Takahashi, H.; Tsubuki, T.; Higashiyama, K. S 1988, 238.
12. Ishii, T.; Kawamura, N.; Matsubara, S.; Utimoto, K.; Kozima, S.; Hitomi, T. JOC 1987, 52, 4416.
13. Wakselman, C.; Nguyen, T. JOC 1977, 42, 565.
14. Keyaniyan, S.; Apel, M.; Richmond, J. P.; De Meijere, A. AG(E) 1985, 24, 770.

Masao Tsukazaki & Victor Snieckus

University of Waterloo, Ontario, Canada

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.