Lithium Butyl(cyano)cuprate


[41742-63-6]  · C5H9CuLiN  · Lithium Butyl(cyano)cuprate  · (MW 153.62)

(organometallic reagent for the addition of an n-butyl group to enones, vinyl epoxides, simple epoxides, vinyl sulfones, and allylic halides)

Solubility: sol diethyl ether, THF at -78 °C.

Preparative Method: the title reagent, like other alkyl or arylcyanocuprates, is prepared at -78 °C from the addition of the alkyl- or aryllithium precursor to 1 equiv anhyd Copper(I) Cyanide.1

Handling, Storage, and Precautions: thermally unstable organocuprate; generated at -78 °C in the absence of moisture and oxygen.

Additions to Epoxides.

The ring-opening reactions of the title reagent (1) with epoxides are typical of most organocuprates in that the less hindered carbon of an epoxide is attacked selectively. The cyclohexene epoxide of eq 1 illustrates this reactivity.2

In the case of the more activated epoxy ester (2), the reagent delivers an n-butyl group a to the ester (eq 2).2

The real uniqueness of the cyano reagent (1) is evidenced by its reactions with vinyl epoxides. In reactions with cyclic vinyl epoxides1 such as 1,3-cyclohexadiene monoepoxide and 1,3-cycloheptadiene monoepoxide, 1,4-addition predominates in ether at -78 °C (eq 3).1,3 These selectivities are possible only in the less polar ether solvent, as illustrated for the latter epoxide.

In a similar fashion, exocyclic vinyl epoxides such as the cyclohexenyl epoxide (3) react regiospecifically with (1) to produce the tertiary alcohol (4) (eq 4).4,5

When enol ethers of keto epoxides are employed as the vinyl epoxide system, the higher alkyl- and arylcyanocuprates, such as (1), add in a trans-1,4-manner for cyclohexyl and cyclopentyl systems. In eq 5 a silyl enol ether of the cyclohexenone epoxide (5) reacts with (1) to produce the adduct (6).6

In the cyclopentenone epoxide system, both the silyl enol ether (7) and the enol phosphate epoxide (8) yield the 1,4-trans-adduct (9) with (1) (eqs 6 and 7).7

Vinyl epoxides which are disubstituted at the terminus of the alkene often react selectively in a 1,2-ring opening, as is the case for the epoxyvinyl sulfone (10) (eq 8).8

Lithium Cyano(isohexyl)cuprate.

By analogy with the n-butylcyanocuprate reagent (1), the isohexyl reagent (11) is easily prepared from the isohexyllithium precursor and 1 equiv of anhyd copper(I) cyanide at -78 °C in ether. A direct application of (11) to the synthesis of the side chain of cholesterol involves the 1,4-addition of (11) to the exo-vinyl epoxide (12) (eq 9).9

In a synthetic application for the preparation of the side chain of a-tocopherol, the isohexylcyanocuprate (11) was added in a 1,4-manner to a (Z)-alkenyl butyrolactone (13) in high yield (eq 10).10

Lithium Cyanophenylcuprate.

As a further extension of the cyanocuprate reagents, the lithium cyanophenylcuprate reagent (14) was easily prepared by adding commercially available Phenyllithium to anhyd copper(I) cyanide at -78 °C in ether. This reagent is usually more thermally stable than the higher alkylcyanocuprates and, therefore, reactions can be performed at temperatures as high as 0-25 °C. The regioselectivity of cyanocuprates towards vinyl epoxides is, by and large, maintained for the cyanophenylcuprate (14). In the case of the exo-vinyl epoxide (15), the 1,4-addition occurs selectively to give (16) in 75% yield (eq 11).4

Other examples involving enol ether epoxides are shown in eqs 12 and 13.6,7 In the case of the enol phosphate of the cyclopentenone epoxide, the regioselectivity is skewed towards the 1,2-product to the extent of 2:1.7

In summary, both the n-butylcyanocuprate reagent (1) and the isohexylcyanocuprate (11) behave consistently in their 1,4-regioselectivity towards cyclic vinyl epoxides. Only the phenylcyanocuprate (14) exhibits mixed selectivity with the enol ethers of cyclopentenone epoxides.

Related Reagents.

Lithium Cyano(dimethylphenylsilyl)cuprate; Lithium Cyano(methyl)cuprate; Lithium Di-n-butylcuprate.

1. Marino, J. P.; Floyd, D. M. TL 1979, 675.
2. Acker, R.-D. TL 1977, 3407.
3. Floyd, D. M. PhD thesis: University of Michigan, 1976.
4. Marino, J. P.; Abe, H. S 1980, 872.
5. Marino, J. P.; Abe, H. JOC 1981, 46, 5379.
6. Marino, J. P.; Jaén, J. C. JACS 1982, 104, 3165.
7. Marino, J. P.; Fernández de la Pradilla, R.; Laborde, E. JOC 1987, 52, 4898.
8. Isobe, M.; Ichikawa, Y.; Funabashi, Y.; Mio, S.; Goto, T. T 1986, 42, 2863.
9. Marino, J. P.; Abe, H. JACS 1981, 103, 2907.
10. Trost, B. M.; Klun, T. P. JOC 1980, 45, 4256.

Joseph P. Marino & David P. Holub

University of Michigan, Ann Arbor, MI, USA

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