1,5-Dilithiopentane1

[2223-58-7]  · C5H10Li2  · 1,5-Dilithiopentane  · (MW 84.02)

(constructing block agent: transformations of carboxyl groups and metal halides into cyclohexane and metallacyclohexane synthetic intermediates, and a,o-bifunctional compounds; in presence of CuI ion, the reagent is transformed into an organobiscuprate)

Alternate Name: 1,5-pentanediyldilithium.

Solubility: sol ether, THF, hydrocarbons.

Form Supplied in: prepared in ether and used in solutions which usually range from 0.5 to 1.2 M.

Analysis of Reagent Purity: titration;2 1H NMR a-CH2 signal d -0.81 (t, J = 9 Hz);3 quenching with chlorotrimethylsilane;3,4 GLC.5

Preparative Methods: was first prepared by direct reaction of 1,5-dibromopentane with Lithium metal at 0 °C in anhydrous ether.4,8 This method was later improved by using lithium metal (4 equiv) containing 1% Na with 1,5-dichloropentane (1 equiv).5 The optimum procedure9 uses a 12.5% excess of lithium and maintains the temperature at 0 °C (eq 1). Yields up to 90% can be obtained by this method, which may also serve to prepare lower analogs.

The Barbier procedure, under ultrasonic irradiation, may also be used. In a particular case, 1,5-dibromopentane (2 equiv), methyl R(-)-2-methyloctanoate (1 equiv) and lithium (8 equiv) were reacted in THF at -25 °C for 25 min (see eq 3).10

1,5-Dilithiopentane can also be prepared by lithium-iodine exchange between t-Butyllithium and 1,5-diiodopentane (eq 2).3 This method requires a temperature of -78 °C and 4 equiv of t-BuLi.2 The excess of reagent is important, as a stoichiometric amount leads to the corresponding cycloalkane almost quantitatively.

The procedure also generates, in excellent yields, lithio compounds from homoallylic-type iodides. Alkyl bromides and secondary iodides may also be used, but yields are lower.

Handling, Storage, and Precautions: solutions are highly flammable; must be stored and handled in the absence of proton sources, carbon acids, and oxygen. Flasks and Schlenk tubes should be flushed with dry Ar or N2. At -20 °C, ether solutions have a useful life of one to four months.5,6 At higher temperature (~30 °C), organolithiums react readily with ethers.7

Synthetic Applications.

1,5-Dilithiopentane converts various electrophiles and bis(electrophiles) into cyclohexane and spirobicyclic compounds. It is also useful for the preparation of a,o-bifunctional compounds and other organobimetallic reagents.

Cyclohexane Derivatives.

1,5-Dilithiopentane reacts as a bis(nucleophile) with geminal bis(electrophile), providing cyclohexane derivatives, as is exemplified in eq 3, with a chiral ester as substrate.10

Cyclohexanone can also be prepared in modest yield from 1,5-dilithiopentane and Carbon Monoxide.11

Unlike smaller rings, six-membered metallacycles are not available through cycloaddition reactions. They are formed by the reaction of metal dihalides with appropriate organobismetallic reagents such as 1,5-dilithiopentane.12 The deuterated 1,5-dilithiopentane in eq 4 was used in a mechanistic study of the thermal decomposition of metallacycles.13

a,o-Bifunctional Compounds.

1,5-Dilithiopentane reacts readily with Chlorotrimethylsilane to produce 1,5-bis(trimethylsilyl)pentane. This reaction has been used to titrate the reagent (eq 5).3,4 1,5-Bis(trimethylstannyl)pentane was produced in a like manner (80%) from Chlorotrimethylstannane.3

1,5-Dilithiopentane is less prone to cyclization than 1,4-dilithiobutane, as is shown by the reactions of the two compounds with Chlorotriphenylsilane.14 Thus 1,5-dilithiopentane gives mainly (75%) 1,5-bis(triphenylsilyl)pentane (eq 6) while the parent compound, under the same conditions, furnishes 1,4-bis(triphenylsilyl)butane in only 19%, the main product of the reaction being the cyclic product 1,1-diphenyl-1-silacyclopentane (see also 1,4-Dilithiobutane).

a,o-Diketones can be easily produced by the reaction of an organobiscuprate with an acyl chloride.15 Thus 1,5-dilithiopentane, in the presence of Phenylthiocopper(I),16 reacts with benzoyl chloride to give 1,7-diphenylheptane-1,7-dione (eq 7).17

The yield of open chain products resulting from the addition of 1,n-dilithioalkane to at least 2 equiv of substrate may be optimized by performing the reaction in dilute solution.18

Heterobimetallic zinc and copper reagents have been prepared from 1,5-diiodopentane.19 The interesting point with this reagent is that the two organometallic moieties have quite different reactivities. It is thus possible to prepare bis(functionalized) compounds by successively reacting the reagent with two different electrophiles. Very good yields (60-80%) have been obtained with various substrates (eq 8) (see also 1,4-Dilithiobutane).

Spiroannulation.

The first published reaction of 1,5-dilithiopentane involved a cyclization. Thus the preparation of 6-silaspiro[5.5]undecane was realized from 1,5-dilithiopentane and 1,1-dichloro-1-silacyclohexane (eq 9).8

1,5-Dilithiopentane and parent dilithio compounds such as 1-lithio-3-(2-lithiophenyl)propane and 1,5-dilithiohex-5-ene can also be used in their bis(heterocuprate) form. In this manner, various spiroketones have been obtained in good to excellent yields.6,15 For example, spiro[5.5]undecan-2-one was synthesized with a 74% yield from 3-chlorocyclohex-2-en-1-one and the bis(heterocuprate) prepared by adding, at -78 °C, a THF solution of 1,5-dilithiopentane to phenylthiocopper, also in THF (eq 10) (see also 1,4-Dilithiobutane).

The direct and stereoselective synthesis of a known key intermediate of the sesquiterpenes b-vetivane, hinesol, and epihinesol was achieved using this methodology.20 The desired cis stereochemistry was obtained, as expected, based on related work (eq 11).21

Related Reagents.

1,4-Bis(bromomagnesio)butane; 1,5-Bis(bromomagnesio)pentane; 1,4-Dilithiobutane.


1. (a) Streitwieser, A. Jr. ACR 1984, 17, 353. (b) Maercker, A.; Theis, M. Top. Curr. Chem. 1987, 138, 1: (c) Wardell, J. L. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed.; Pergamon: Oxford, 1982; Vol. 1, Chapter 2.
2. (a) Gilman, H.; Cartledge, F. K. JOM 1964, 2, 447. (b) Watson, S. C.; Eastham, J. F. JOM 1967, 9, 165. (c) Whitesides, G. M.; Casey, C. P.; Krieger, J. K. JACS 1971, 93, 1379.
3. Negishi, E.; Swanson, D. R.; Rousset, C. J. JOC 1990, 55, 5406.
4. West, R.; Rochow, E. G. JOC 1953, 18, 1739.
5. McDermott, J. X.; Wilson, M. E.; Whitesides, G. M. JACS 1976, 98, 6529.
6. Wender, P. A.; White, A. W. JACS 1988, 110, 2218.
7. Bates, R. B.; Kroposki, L. M.; Potter, D. E. JOC 1972, 37, 560.
8. West, R.; Rochow, E. G. N 1953, 40, 142.
9. Wender, P. A.; White, A. W.; McDonald, F. E. OS 1992, 70, 204.
10. de Souza-Barboza, J. C.; Luche, J.-L.; Pétrier, C. TL 1987, 28, 2013.
11. Ryang, M.; Sawa, Y.; Hasimoto, T.; Tsutsumi, S. BCJ 1964, 37, 1704.
12. Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Applications of Organotransition Metal Chemistry; University Science Books: Mill Valley, CA, 1987; Chapter 9.
13. Grubbs, R. H.; Miyashita, A. JACS 1978, 100, 7418.
14. Wittenberg, D.; Gilman, H. JACS 1958, 80, 2677.
15. (a) FF 1986, 13, 345-50. (b) Kim, S.; Lee, J. I. JOC 1983, 48, 2608.
16. (a) Posner, G. H.; Whitten, C. E.; Sterling, J. J. JACS 1973, 95, 7788: (b) Posner, G. H.; Brunelle, D. J.; Sinoway, L. S 1974, 662.
17. Wender, P. A.; Eck, S. L. TL 1977, 1245.
18. Dietrich-Buchecker, C. O.; Sauvage, J.-P. TL 1983, 24, 5095.
19. AchyuthaRao, S.; Knochel, P. JOC 1991, 56, 4591.
20. Canonne, P; Boulanger, R.; Angers, P. TL 1991, 32, 5861.
21. (a) Lafontaine, J.; Mongrain, M.; Sergent-Guay, M.; Ruest, L.; Deslongchamps, P., CJC 1980, 58, 246. (b) Canonne, P.; Bernatchez, M. JOC 1987, 52, 4025.

Persephone Canonne & Paul Angers

Université Laval, Sainte-Foy, Québec, Canada



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