Cyanomethylcopper1

CuCH2CN

[35219-76-2]  · C2H2CuN  · Cyanomethylcopper  · (MW 89.58)

(reagent for the cyanomethylation of allyl halides2)

Preparative Methods: by the reaction of cyanomethyllithium (Lithioacetonitrile) and Copper(I) Iodide in THF at -25 °C,2 or by the thermal decarboxylation of Copper(I) Cyanoacetate.3

Handling, Storage, and Precautions: can be prepared in two forms, a red solution in THF or an insoluble dark yellow solid. The solid form is stable in the absence of air to 100 °C, but both forms are air- and moisture-sensitive. Use in a fume hood.

General Discussion.

Although both the above preparations produce cyanomethylcopper, the physical characteristics of the specific reagent produced by each method are markedly different, as is the reactivity. The cyanomethylcopper obtained by transmetalation of the lithio precursor in THF is a brick-red solution which gives a negative Gilman test. The soluble reagent is reactive toward allylic electrophiles, but does not react with benzyl bromide, esters, vinyl bromides, or vinyl iodides (eqs 1-3).

Cyanomethylcopper produced by the decarboxylation route is a dark yellow solid which is insoluble in most organic solvents. Addition of 1 equiv of Lithium t-Butoxide to a suspension of the solid reagent in DMF results in a homogeneous solution which does react with benzyl bromide and iodobenzene (no yields are given). The isolated solid cyanomethylcopper is stable under nitrogen to approximately 100 °C, but is rapidly decomposed when exposed to air. The addition of acetic acid results in formation of acetonitrile and copper(I) acetate. Cyanomethylcopper can also be obtained by the reaction of copper(II) methoxide and 2 equiv of cyanoacetate. The initial copper acetate salt decomposes upon heating in DMF to generate cyanomethylcopper, succinonitrile, and carbon dioxide.3 Decomposition of copper cyanoacetate in the presence of propene oxide produces cyanomethylcopper and propylene carbonate; therefore, copper cyanoacetate also functions as a source of activated carbon dioxide (eq 4).4 Control reactions revealed that cyanomethylcopper was required for the transcarboxylation reaction. Cyanomethylcopper formed independently (by the decarboxylation route described above) served as a catalyst for the reaction of propene oxide with carbon dioxide gas. Other sources of copper(I) examined, such as CuCN and CuCl, were ineffective as catalysts and did not produce any propylene carbonate.

Cyanomethylation.

Cyanomethylcopper is a relatively unreactive organocopper reagent, similar to other stabilized alkylcopper species such as Ethoxycarbonylmethylcopper. The reagent is ideally suited for cyanomethylation of allylic halides. Reaction occurs cleanly by direct substitution (SN2) without significant competing allylic transposition (SN2 alkylation). In a key step in the synthesis of cembrane lactones, Marshall and co-workers reported that cyanomethylcopper gave only the product arising from direct displacement of an allyl bromide, while other approaches to the nitrile product resulted in considerable amounts of the SN2 alkylation product (eq 5).5 The synthesis of the alkaloid peramine, the principal insect feeding deterrent isolated from perennial ryegrass, was achieved by an allylic displacement reaction on a 2-methylpyrrolo[1,2-a]pyrazin-1(2H)-one ring system using cyanomethylcopper (eq 6).6

Cyanomethylcopper does not react with carbonyl groups; however, an iron derivative has been shown to be selective for addition to aldehydic carbonyl groups in the presence of ketones.7 Knochel and co-workers have achieved the preparation of chain-extended nitriles by the reaction of cyanomethylcopper with Iodomethylzinc Iodide.8 Subsequent reaction with a variety of electrophiles results in very good yields of products formally derived from 2-cyanoethylcopper. This reagent is more reactive than the parent cyanomethylcopper and undergoes conjugate addition reactions (eq 7) as well as alkylation reactions with allyl halides (eq 8). Reaction of copper cyanide solubilized with Lithium Chloride and iodomethylzinc iodide generates the parent cyanomethylcopper reagent in situ, thereby avoiding the need to prepare cyanomethyllithium.


1. (a) Posner, G. H. OR 1972, 19, 1. (b) Posner, G. H. OR 1975, 22, 253. (c) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (d) Normant, J. F. S 1972, 63. (e) Yamamoto, Y. AG(E) 1986, 25, 947. (f) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents; Wiley: New York, 1980.
2. Corey, E. J.; Kuwajima, I. TL 1972, 487.
3. Tsuda, T.; Nakatsuka, T.; Hirayama, T.; Saegusa, T. CC 1974, 557.
4. Tsuda, T.; Chujo, Y.; Saegusa, T. CC 1976, 415.
5. Marshall, J. A.; Crooks, S. L.; DeHoff, B. D. JOC 1988, 53, 1616.
6. Brimble, M. A.; Rowan, D. D. CC 1988, 978.
7. Kauffmann, T.; Kieper, H.; Pieper, H. CB 1992, 125, 899.
8. Knochel, P.; Jeong, N.; Rozema, M. J.; Yeh, M. C. P. JACS 1989, 111, 6474.

Russell J. Linderman

North Carolina State University, Raleigh, NC, USA



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