Ethyllithium1

EtLi

[811-49-4]  · C2H5Li  · Ethyllithium  · (MW 36.01)

(organometallic reagent used in 1,2-2 and 1,4-additions;2a,b,3 synthesis of various transition metal complexes;4 used as a base in the preparation of 2-bromofuran,5a with phenylallene to form terminal alkynes,5b as a catalyst in conjunction with TMEDA in the alkylation of amines with alkenes;5c used for the in situ preparation of lithium diethylcuprate,2a,3b,6 and EtCu(CN)Li.BF36)

Physical Data: mp 95 °C; sublimes at 80 °C/10-3 mmHg.

Solubility: sol hydrocarbons, THF, Et2O.

Form Supplied in: approx. 1 M light brown solution in benzene.

Preparative Methods: prepared from alkyl halides and elemental lithium.8a-e

Purification: recrystallized from hexane8e or cyclohexane8c,d under argon at 4 °C to give a white solid.

Handling, Storage, and Precautions: the dry solid is extremely pyrophoric on exposure to air. Solutions are flammable, corrosive and react violently with water and should be used immediately. Storage for as little as one week at low temperatures can lead to up to one-half of the reagent being converted to ethane, ethylene, and the enolate of acetaldehyde.3a,8a,d,e

Nucleophilic Addition.

Ethyllithium is known to add as a nucleophile to a,b-unsaturated ketones in both a 1,2- and 1,4-manner. Addition of Hexamethylphosphoric Triamide (HMPA) enhances selectivity of 1,4-addition, as illustrated in eq 1. This selectivity is also affected by coordinating ability of the solvent. A general order for increasing 1,4-selectivity is EtLi (pet. ether) <= EtLi (Et2O) <= EtLi (1 equiv HMPA) <= EtLi (2 equiv HMPA).2a Similar results were obtained for reactions with MVK, 2-cyclohexen-1-one, and 2-cycloocten-1-one.

Ethyllithium undergoes nucleophilic addition with pyridine to afford exclusively the 1,2-adduct. When used in conjunction with diethylmagnesium, however, significant amounts of 1,4-adducts are observed (eq 2). This mixed organometallic system also provides enhanced 1,4-selectivity when reacted with 2-cyclohexen-1-one.2b

1,2-Addition of ethyllithium to triethyl phosphate is known to generate precursors for Horner reagents, as shown in eq 3.2c,d

Addition to benzoquinone is exclusively 1,2- with the second addition favoring the cis isomer by a 4:1 ratio.2e Also noted is 1,2-addition to amides followed by dehydration of the resulting aminal.2f Ethyllithium acts first as a base and then as a nucleophile in its reaction with aldehyde-O-alkyloximes. Ethyl ketones are prepared by their reaction with ethyllithium followed by hydrolysis of the imine (eq 4).2g

Azophilic 1,2-addition has been observed for the addition of ethyl- and n-butyllithium to fluorenimines.2h Superior diastereoselectivity to titanium and copper reagents is exhibited by EtLi in its 1,2-addition to acrolein dimer during chelation-free formation of the dihydropyranols illustrated in eq 5. Complementary selectivity is possible when other reagents are employed.2i

Metal-mediated asymmetric 1,2-nucleophilic attack by ethyllithium at C-2 (eqs 6 and 7) occurs exclusively exo to the Fe(CO)3 group of (vinylketenimine)tricarbonyliron(0) complexes to give chiral quaternary centers of high optical purity.2j

On the contrary, chelation-controlled 1,4-addition of ethyllithium to acylketene acetals with diastereoselective enolate trapping has been reported (eq 8).3a,b

Similarly, tandem 1,4-additions of alkyllithium reagents to chiral aromatic and unsaturated oxazolines followed by electrophilic trapping with Iodomethane proceed in good yield and with excellent diastereoselectivity (eq 9).3c

Synthesis of Organometallic Complexes.

Ethyllithium has been employed in the synthesis of ethylenic organometallic compounds,4 including a Ziegler-Natta polymerization precursor complex that contains both an alkyl ligand and a coordinated alkene (eq 10),4a and a hydridobis(ethylene)rhenium(I) complex (eq 11).4d

Use as a Base.

A clean procedure for the preparation of 2-bromofuran involves the lithiation of furan in diethyl ether followed by treatment with elemental Bromine (eq 12).5a Solutions of other alkyllithium reagents are impractical for this procedure due to the necessity of removal of less volatile solvents prior to their subsequent replacement by Et2O.

Reaction of phenylallene with two equivalents of ethyllithium followed by reaction with reactive electrophiles provides access to terminal alkynes (eq 13).5b The intermediate dianion readily undergoes alkylation exclusively at the sp3 center.

Ethyllithium serves as catalytic base in the alkylation of amines with alkenes in the presence of TMEDA.5c

Preparation of Other Reagents.

The in situ preparations of Lithium Diethylcuprate2a,6 and EtCu(CN)Li.BF37 are widely documented. A chiral mixed ethylcuprate was used to produce (R)-(+)-3-ethylcyclohexanone with high selectivity (ee >95%) only when freshly prepared and recrystallized ethyllithium was used to make the reagent. Trace alkoxide contamination lowered the ee to 9%.6b

Related Reagents.

Diethylzinc.


1. FF 1975, 5, 306. FF 1975, 5, 324. FF 1981, 9, 84. FF 1988, 13, 177.
2. (a) Ogawa, M.; Takagi, M.; Matsuda, T. T 1973, 29, 3813. (b) Richey, H. G., Jr.; Farkas, J., Jr. OM 1990, 9, 1778. (c) Tay, M. K.; About-Jaudet, E.; Collignon, N.; Teulade, M.-P.; Savignac, P. SC 1988, 18, 1349. (d) Teulade, M.-P.; Savignac, P.; About-Jaudet, E.; Collignon, N. SC 1989, 19, 71. (e) Alonso, F.; Yus, M. T 1991, 47, 7471. (f) Shibagaki, M.; Matsushita, H.; Kaneko, H. H 1986, 24, 2315. (g) Itsuno, S.; Miyazaki, K.; Ito, K. TL 1986, 27, 3033. (h) Dai, W.; Srinivasan, R.; Katzenellenbogen, J. A. JOC 1989, 54, 2204. (i) Singh, S. M.; Oehlschlager, A. C. CJC 1988, 66, 209. (j) Richards, C. J.; Thomas, S. E. TA 1992, 3, 143.
3. (a) Konopelski, J. P. TL 1991, 32, 465. (b) Eid, C. N. Jr.; Konopelski, J. P. TL 1991, 47, 975. (c) Meyers, A. I.; Schmidt, W.; McKennon, M. J. S 1993, 2, 250.
4. (a) Spencer, M. D.; Morse, P. M.; Wilson, S. R.; Girolami, G. S. JACS 1993, 115, 2057. (b) Maryin, V. P.; Petrovskii, P. V. JOM 1992, 441, 125. (c) Richards, C. J.; Thomas, S. E. TA 1992, 3, 143. (d) Komiya, S.; Baba, A. OM 1991, 10, 3105. (e) Uemura, M.; Miyake, R.; Shiro, M.; Hayashi, Y. TL 1991, 32, 4569.
5. (a) Verkruijsse, H. D.; Keegstra, M. A.; Brandsma, L. SC 1989, 19, 1047. (b) Brandsma, L.; Mugge, E. RTC 1973, 92, 628. (c) Lehmkuhl, H.; Reinehr, D. JOM 1973, 55, 215.
6. (a) Corey, E. J.; Naef, R.; Hannon, F. J. JACS 1986, 108, 7114. (b) Kant, J. JOC 1993, 58, 2296. (c) Oppolzer, W.; Mills, R. J.; Pachinger, W.; Stevenson, T. HCA 1986, 69, 1542. (d) Oppolzer, W.; Barras, J.-P. HCA 1987, 70, 1666.
7. Ibuka, T.; Akimoto, N.; Tanaka, M.; Nishii, S.; Yamamoto, Y. JOC 1989, 54, 4055.
8. (a) Gronert, S.; Streitwieser, A., Jr. JACS 1986, 108, 7016. (b) Masamune, S.; Choy, W. Aldrichim. Acta 1982, 15, 47. (c) Lewis, H. L.; Brown, T. L. JACS 1970, 92, 4664. (d) Brown, T. L.; Rogers, M. T. JACS 1957, 79, 1859. (e) Talalaeva, T. V.; Kocheskov, K. A. JGU 1953, 53, 399. (f) Ziegler, K.; Gellert, H.-G. LA 1950, 567, 179.

K. Sinclair Whitaker

Wayne State University, Detroit, MI, USA

D. Todd Whitaker

Detroit Country Day School, Beverly Hills, MI, USA



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