Zinc-Copper(I) Chloride


[7440-66-6]  · Zn  · Zinc-Copper(I) Chloride  · (MW 65.39) (CuCl)

[7758-89-6]  · ClCu  · Zinc-Copper(I) Chloride  · (MW 99.00)

(forms zinc-copper couple;1 thence capable of initiating Reformatsky2 and related reactions, and Simmons-Smith methylenation3)

Physical Data: see Copper(I) Chloride and Zinc

Zinc-Copper Couple.1

A typical procedure involves mixture of zinc, usually activated,4 and a catalytic amount of CuCl, often 10 mol %, before introduction of the organic halide appropriate for subsequent reaction. Enhancement of the procedure can be effected by the use of ultrasound,5 substitution of Silver(I) Acetate2c,6 for CuCl, or, in certain cases, incorporation of Chlorotrimethylsilane.7

Reformatsky Reactions.2

The multiply halogenated ester (1) reacts with aldehydes in the presence of Zn/CuCl, 4Å molecular sieve (MS), and Acetic Anhydride to give unsaturated esters (2) (eq 1).2a The double bonds are predominantly or exclusively in the (Z) configuration. Omission of Ac2O from the reaction leads to lower yields of (2) and substantial amounts of b-hydroxycarboxylate. Ketones react poorly in this procedure (20%). Similar reactivity has been demonstrated with the ester CF3CCl2CO2Me,2b giving a-trifluoromethyl-a,b-unsaturated esters. The a-halo ketones (3) react similarly (eq 2),2c,2d but only with aldehydes; ketones react only if CuCl is replaced by AgOAc and Diethylaluminum Chloride is also required.

Reformatsky-Type Reaction of an Allylic Halide.2e

The allylic trihalide (4) undergoes exactly analogous reactions with both aldehydes and ketones, although the latter react more sluggishly, and usually in lower yield (eq 3). In some cases, AgOAc is still preferred to CuCl, but the reagents seem more equivalent in this case than in those cited above. Reactivity at the a-position of the allylzinc reagent is noteworthy, since g-alkylation of carbonyls is more usual.8

a,a-Dibromo Ketone Cycloaddition.5,7,9

Zn/CuCl can cause a cycloaddition reaction between an a,a-dibromo ketone and a suitable diene, as in eq 4, leading to seven-membered rings. A similar reaction, but superior in terms of yield, uses Nonacarbonyldiiron,10 but this reagent is appreciably more toxic and expensive. The Zn/CuCl reaction is substantially improved by addition of Me3SiCl7 or, even better, ultrasonication.5

Alkene Acylation.11

Acylation of alkenes by acyl chlorides (eq 5) is promoted by zinc activated by any of a number of reagents, the best of which appears to be Zn/CuCl and Diiodomethane. Although this normally gives rise to the so-called Simmons-Smith reagent (see below),3 no trace of alkene methylenation is observed under these conditions. Other catalysts such as Aluminum Chloride, Zinc Iodide, or Zinc Chloride may also effect the reaction in certain cases, but with inferior yields.

Simmons-Smith Reaction.3

This reaction, as demonstrated originally for cyclohexene (eq 6), is treated at length elsewhere (see Zinc/Copper Couple and Diiodomethane).

1. Rawson, R. J.; Harrison, I. T. JOC 1970, 35, 2057.
2. (a) Ishihara, T.; Kuroboshi, M. CL 1987, 1145. (b) Allmendinger, T.; Lang, R. W. TL 1991, 32, 339. (c) Kuroboshi, M.; Ishihara, T. TL 1987, 28, 6481. (d) Kuroboshi, M.; Ishihara, T. BCJ 1990, 63, 428. (e) Ishihara, T.; Miwatashi, S.; Kuroboshi, M.; Utimoto, K. TL 1991, 32, 1069.
3. Simmons, H. E.; Cairns, T. L.; Vladuchick, S. A. OR 1973, 20, 1.
4. Erdik, E. T 1987, 43, 2203.
5. Joshi, N. N.; Hoffmann, H. M. R. TL 1986, 27, 687.
6. Denis, J.; Girard, C.; Conia, J. M. S 1972, 549.
7. Giguere, R. J.; Rawson, D. I.; Hoffmann, H. M. R. S 1978, 902.
8. Courtois, G.; Miginiac, L. JOM 1974, 69, 1.
9. Hoffmann, H. M. R.; Clemens, K. E.; Smithers, R. H. JACS 1972, 94, 3940.
10. (a) Noyori, R.; Makino, S.; Takaya, H. JACS 1971, 93, 1272. (b) Takaya, H.; Makino, S.; Hayakawa, Y.; Noyori, R. JACS 1978, 100, 1765.
11. Shono, T.; Nishiguchi, I.; Sasaki, M.; Ikeda, H.; Kurita, M. JOC 1983, 48, 2503.

Peter Ham

SmithKline Beecham Pharmaceuticals, Harlow, UK

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