1,4-Dilithiobutane1

[2123-72-0]  · C4H8Li2  · 1,4-Dilithiobutane  · (MW 69.99)

(converts various functional groups into cyclopentanes and synthetic metallacyclopentane intermediates; useful synthon for preparing a,o-bifunctional compounds; precursor of other organobimetallic reagents)

Alternate Name: 1,4-butanediyldilithium.

Solubility: sol ether, THF, hydrocarbons.

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

Analysis of Reagent Purity: titration;2,3 1H NMR: a-CH2 signals at d -0.8 to -1.1 ppm;4 quenching with chlorotrimethylsilane;2,3,5 GLC.6

Preparative Method: see 1,5-Dilithiopentane.

Handling, Storage, and Precautions: solutions are highly flammable and 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 1 to 4 months.5,7 At higher temperature (~30 °C), organolithiums react readily with ethers.8

Structure.

MO calculations suggest for 1,4-dilithiobutane a doubly bridged structure which is 34.6 kcal mol-1 more stable than the extended form (eq 1).9 That structure, along with others,1a would be responsible for the relative stability of the reagent.

Synthetic Applications.

Organolithium and organomagnesium bifunctional compounds usually react with various carbon electrophiles and metal halides in a comparable manner, whether as such or as biscuprates, and are often used interchangeably. However, because of a generally more convenient method of preparation, di-Grignard reagents are more widely used in organic synthesis (see 1,4-Bis(bromomagnesio)butane and 1,5-Bis(bromomagnesio)pentane).

Cyclopentane Derivatives.

1,4-Butanediyldilithium can directly lead to cyclopentane derivatives by consecutive additions to dielectrophiles such as esters, lactones, and anhydrides, to give 1-substituted cyclopentanols. This annulation strategy has been successfully used for the synthesis of spiro compounds. Thus a spirobutenolide is readily prepared from 1-ethoxy-2,5-dihydrofuran-2-one and 1,4-dilithiobutane (eq 2).10

Organobiscuprates.11

1,4-Dilithiobutane, as organobiscuprate, reacts directly with Carbon Monoxide to give cyclopentanone, but yields are low (eq 3).12 For the formation of cycloalkanones, the reaction between a metallacycle and carbon monoxide is much more efficient (see eq 5, below).

In presence of Phenylthiocopper(I) (2 equiv),13 1,4-dilithiobutane affords the corresponding organobis(heterocuprate), as formulated in eq 4, which reacts with b-bromocyclopent-2-en-1-one, 3-chlorocyclohex-2-en-1-one, and 3-chloro-5,5-dimethylcyclohex-2-en-1-one to form spiro[4.4]nonan-2-one, spiro[4.5]decan-7-one, and 9,9-dimethylspiro[4.5]decan-7-one (eq 4), respectively, in excellent yields.14 This annulation methodology was applied to 3-bromo-2-methylcyclopent-2-en-1-one and 3-chloro-2-methylcyclohex-2-en-1-one to form 1-methylspiro[4.4]nonan-2-one and 6-methylspiro[4.5]decan-7-one with similar results.

Metallacyclopentanes.15

The synthesis of various metallacyclopentanes starting with metal halides constitutes an important and useful application of 1,4-dilithiobutanes.16 These metallacycles readily produce cyclopentanones via carbonylation. The formation of hexahydroindan-3-one illustrates such an approach (eq 5).5

The reaction of 1,4-dilithiobutane with Chlorotriphenylsilane provides, as major product, the corresponding silacyclopentane rather than the expected 1,4-bis(triphenylsilyl)butane (eq 6).17

a,o-Bifunctional Compounds.

1,4-Dilithiobutane has also been used for the preparation of a,o-bifunctional compounds such as 1,6-hexanedioic acid and 1,6-hexanedial (see 1,5-Dilithiopentane). This procedure is typified by the transformation of 1,10-phenanthroline to 1,4-bis(1,10-phenanthrolinyl)butane, which was further transformed to a molecular trefoil knot (eq 7).18

Organocopper/Zinc Reagents.19

1,4-Heterobimetallic reagents of zinc and copper were prepared by reaction of 1,4-diiodobutane with Zinc dust in THF and subsequent transmetalation with CuCN.2LiCl (see Copper(I) Cyanide) (eq 8). This reagent, which contains two different metals, undergoes selective coupling with electrophiles (E1) such as aldehydes, iodoalkynes, enones, and nitroalkenes, leading to a monocoupled zinc and copper organometallic compound. Exposure of this intermediate to a second electrophile (E2) provides the corresponding polyfunctional compound. The second electrophile may be Allyl Bromide, 3-iodocyclohex-2-en-1-one, Chlorotrimethylstannane, or benzaldehyde.20 Less than 5% of symmetrical dicoupling adducts are observed as byproducts.

A typical example of this type of coupling involves the use of this reagent with cyclohex-2-en-1-one (E1) and a-(bromomethyl)acrylate (E2) (eq 9).

Related Reagents.

The quaternization methodology based on organobis(heterocuprates) is fairly general. Thus spiroannulation can be achieved with a variety of unsaturated organodilithio reagents such as 1,4-dilithiopent-4-ene (eq 10), 1-lithio-2-(2-lithiophenyl)ethane (eq 11), and 2,2-dilithiobiphenyl (eq 12) providing, respectively, 1-methylenespiro[4.5]decan-7-one, spiro[cyclohexane-1,1-indan]-3-one, and spiro[cyclohexane-1,9-fluoren]-3-one.12

See also 1,4-Bis(bromomagnesio)butane, 1,5-Bis(bromomagnesio)pentane, and 1,5-Dilithiopentane.


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14. Wender, P. A.; Eck, S. L. TL 1977, 1245.
15. Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. In Principles and Applications of Organotransition Metal Chemistry; University Science Books: Mill Valley, Ca, 1987; pp 459-520.
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17. Wittenberg, D.; Gilman, H. JACS 1958, 80, 2677.
18. Dietrich-Buchecker, C. O.; Sauvage, J. P. AG(E) 1989, 28, 189.
19. (a) FF 1990, 15, 229. (b) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. JOC 1988, 53, 2390.
20. AchyuthaRao, S.; Knochel, P. JOC 1991, 56, 4591.

Persephone Canonne & Paul Angers

Université Laval, Sainte-Foy, Québec, Canada



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