Copper(I) Iodide1


[7681-65-4]  · CuI  · Copper(I) Iodide  · (MW 190.45) (.PBu3)

[21591-31-1]  · C12H27CuIP  · Copper(I) Iodide-Tributylphosphine  · (MW 392.81) (.(SBu2)2)

[35907-81-4]  · C16H36CuIS2  · Copper(I) Iodide-Bis(dibutyl sulfide)  · (MW 483.11)

(the classical precursor for organocopper(I) and organocuprate reagents1)

Alternate Name: cuprous iodide.

Physical Data: mp 605 °C; d 5.620 g cm-3.

Solubility: insol H2O and most organic solvents; partially sol dimethyl sulfide (DMS).

Form Supplied in: off-white to grayish solid; 99.999% grade available.

Handling, Storage, and Precautions: maintenance of a dry N2 or Ar atmosphere is recommended.

General Discussion.

The first organocopper compound to be isolated, Phenylcopper, was prepared in 1923 by Rene Reich from Phenylmagnesium Bromide and CuI.2 In 1936, Gilman repeated the preparation of PhCu from CuI,3a and in 1952 he prepared Methylcopper and Lithium Dimethylcuprate from CuI and 1 and 2 equiv of Methyllithium, respectively.3b An improved preparation of halide-free MeCu and Me2CuLi from CuI has recently been reported,4 and an appreciation of the role of the lithium salt from the preparation in the structure and reactivity of the reagent has developed in recent years.5-10 Therefore it has been proposed that any salt from the metathesis reaction used to prepare the organocopper reagent should be explicitly shown in the formula, e.g. Ph2CuLi.LiI,5 PhCu/LiI,6 Bu2CuLi.LiBr,7 Bu2CuNa.NaCN,8a etc. Unfortunately, many of the tables in the latest Organic Reactions chapter on organocopper reagents do not list the CuI salt from which the reagents were prepared.1a

Interest in organocopper reagents was rekindled in 1966 when House and Whitesides9 showed that organocuprates were intermediates in what we propose to call the Kharasch reaction, the Cu-catalyzed 1,4-addition of Grignard reagents to enones.11 They also reported the development of two organocopper reagents which have the stoichiometry Li+Me2Cu- and MeCuP(n-Bu)3.9 Both of these classes of reagents are important today (see below). Corey and Posner also used CuI to prepare Me2CuLi.LiI12 and Bu2CuLi.LiI,13 which were coupled with alkyl halides and iodobenzene. These initial reports of the synthetic value of organocopper reagents for selective C-C bond formation led to an explosion of applications,1a-g which like the big bang is still expanding today. The principal applications of organocopper reagents to C-C bond formation in the areas of conjugate addition to a,b-unsaturated carbonyl compounds, carbocupration of alkynes, and coupling reactions with oxiranes and alkyl, alkenyl, and aryl halides have been well reviewed.1a -h While CuI has been supplanted by CuBr.DMS (see Copper(I) Bromide) and Copper(I) Cyanide for many purposes, it is still one of the main precursors that should be tried when optimizing an organocopper synthesis.7

In addition to the ate complexes prepared from 2 equiv of RLi, the organocopper(I) compounds RCu, prepared from 1 equiv of RLi and CuI, have found synthetic application in the presence of additives, which enhance the reactivity of these otherwise relatively unreactive compounds. Both Lewis bases and Lewis acids1d have been used for this purpose, and their utility has been extended to the organocuprates as well. Examples of the former are phosphines, such as Tri-n-butylphosphine,14 and sulfides, such as dibutyl sulfide15 and Dimethyl Sulfide;6,16a examples of the latter are Boron Trifluoride17,18 and Aluminum Chloride.17a,19 Chlorotrimethylsilane (TMSCl) is a useful additive,20,21 especially in conjunction with HMPA.6,22 In analogy with these major additives, triethylphosphine,23a triphenylphosphine,23b,24 tricyclohexylphosphine,24 dppe,24,25 triethyl phosphite,26 diisopropyl sulfide,16b triethylboron,27 trimethylaluminum,28 titanium tetrachloride,17b,18a TMSCl-DMAP,22 TMSCl-TMEDA,29 TMSI,30,31 and TMSCN31 have been used. One unique phosphine is polymer-supported RPPh2,32 where R is the polymer backbone.

The addition of BF3 improves some of the usual organocopper reactions,17 and it enables some unprecedented ones, e.g. the direct alkylation of allylic alcohols.17c It also favors 1,4- over 1,6-addition to methyl sorbate: 1,6-addition predominates with Bu2CuLi.LiI,17b and also with BuMgBr/CuCl,11a but 1,4-addition is observed for BuCu.BF3.17b One particularly interesting application of the BF3 procedure is the conjugate addition of CuI aldimines to a,b-unsaturated carbonyl compounds (eq 1), which after hydrolysis gives 1,4-diketones.18b

In some cases the additives improve solubility; in other cases, entirely new reagents result. For example, PhCu is insoluble in ether, but it is soluble in DMS, where it has been shown to be an equilibrium mixture of (PhCu)4 and (PhCu)3.25 When prepared from CuBr or CuCN in DMS, the product is Li-free, due to the precipitation of LiBr or LiCN from DMS.6 This Li-free PhCu is relatively unreactive compared to the reagent prepared from CuI, PhCu/LiI, which still contains the LiI.6 This LiI may be considered an activating additive. The LiI present in Me2CuLi.LiI also has an important effect in conjugate addition reactions, as the percentage of 1,2-addition can be significant for halide-free organocuprates.4

The LiI in PhCu/LiI is not incorporated into the organocopper(I) clusters;6 however, in the case of Ph2CuLi.LiI, 13C NMR shows that both I-containing (major) and I-free (minor) clusters are present.5 House found that although the conjugate addition of lithium dimethylcuprate to a,b-unsaturated ketones appears to require no other species in the reaction solution, Trimethyl Phosphite and Tri-n-butylphosphine complexes of methylcopper will undergo conjugate addition only if various salts such as Lithium Iodide, Lithium Bromide, Magnesium Bromide, or Lithium Cyanide are present in the reaction medium.10

Organocopper reagents are assuming an increasing role in asymmetric synthesis and many of the procedures involve complex mixtures containing one or more of the additives discussed above.15,17a,18a,c This area has been reviewed recently,1b so we highlight one especially interesting example here, the enantiocontrolled synthesis of quaternary carbon centers via the asymmetric conjugate addition of organometallic reagents to enantiomerically pure 2-(arylsulfinyl)cycloalkenones.33 Posner has noted that although Me2CuLi.LiI and Me5Cu3Li2 work well, Me2CuLi.LiCN and MeCu.BF3 do not. He concludes that no one type of organocopper reagent will be universally preferred over others for all different kinds of carbon-carbon bond-forming reactions.33

Tandem b-addition-a-functionalization reactions are an important strategy for rapidly building molecular complexity.1c A particularly impressive example (eq 2) is the three component coupling used by Suzuki and Noyori to prepare prostaglandins,14c,d which owes its success to the use of derivatives of House's RCu(PBu3).9,10,14a,b An interesting intramolecular version involving conjugate addition-cycloacylation of alkynic diesters to give highly functionalized cyclopentenones has been developed by Crimmins.34 Tandem organocopper addition-electrophilic functionalization of alkynes is well established,1a,f and Meyers has even performed such a sequence on a benzyne.35

Useful applications of organocopper reagents to carbohydrate chemistry have been made by the Kocienski and Fraser-Reid groups. In the former case, an oxirane ring was opened regio- and stereoselectively.36 In a contraintuitive finding, the latter group reported that the homogeneous system using the soluble CuI.PBu3 complex was less satisfactory than the heterogeneous system based upon CuI for the conjugate addition-alkylation of hex-2-enopyrano-4-ulosides.37

Some exciting recent developments extending the scope of organocopper chemistry involve CuI. Rieke has reported the preparation of RCu.PBu3 from a highly reactive copper intermediate prepared via the reduction of CuI.PBu3.23,38 Ebert has used a similar procedure to prepare remote ester and ketone functionalized organocopper reagents.39

Alkenes with perfluoroalkyl substituents have been prepared by the reaction of perfluoroalkyl iodides with terminal alkynes in the presence of ultrasonically dispersed Zinc and CuI.40a A general procedure for the formation of organocopper reagents from alkyl and aryl halides and Lithium metal in the presence of CuI or 1-Pentynylcopper(I) under ultrasonic irradiation has also been described.40b

One of the extraordinary things about displacement reactions mediated by CuI is the fact that they occur with both facility at sp3 and sp2 centers, as eqs 3 and 4 illustrate. Eq 3 involves a classic SN2-like reaction, but is noteworthy because of the complexity of the other functionality in the substrate, an a-amino acid derivative.15a Eq 4, the alkylation of alkenyl triflates,41 adds a versatile alternative to the alkylation of alkenyl halides.1a,g

Good reviews are available of stoichiometric cuprates prepared from lithium reagents,1a stoichiometric cuprates prepared from Grignard reagents,1a and the use of Grignard reagents with catalytic amounts of CuI salts.1a,e Sadly, direct comparisons have not been made among all the variations. When one adds further variables such as which CuI salt is used, what halide is present in the Grignard reagent, and whether the stoichiometry is 2:1 or 1:1, it is easy to see that the choice of conditions is a complex problem, even before all the possible additives are considered. The best advice we can give the synthetic chemist is to try several sets of conditions based upon similar examples in the literature. Fortunately, an exhaustive compilation has been published recently.1a

A species of intermediate stoichiometry between organocopper(I) and organocuprate(I) (RCu and R2CuLi, respectively) has been described as Me5Cu3Li2 = MeCu + (Me2CuLi)2. While the structure of the reagent has yet to be determined, it has proved to be useful for the conjugate addition of Me to a,b-unsaturated aldehydes.42

In recent work that is related to the organocuprate chemistry discussed above, Miura et al. have reported the CuI-catalyzed reaction of aryl and vinyl iodides with terminal alkynes,43a and of aryl iodides with active methylene compounds.43b

Finally, not all applications of CuI involve organocuprates or related reagents. For example, Corey used CuI to catalyze intramolecular diazoalkene cyclization reactions,44 and Yates used CuI to catalyze the Wolff rearrangement of diazo ketones.45 House recommended CuI.(SBu2)2 for the intermolecular cyclopropanation of alkenes with a-diazo ketones. The intermediates are undoubtedly organocopper species of some kind, perhaps Cu-carbene complexes; however, it should be noted that Cu0 and CuII are more commonly used as catalysts in conjunction with diazo compounds.1i

Related Reagents.

See the copper(I) iodide combination reagents following this entry; also Copper(I) Bromide and Copper(I) Chloride (and their combination reagents), Copper(I) Cyanide, and Copper(I) Trifluoromethanesulfonate.

1. (a) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (b) Rossiter, B. E.; Swingle, N. M. CRV 1992, 92, 771. (c) Chapdelaine, M. J.; Hulce, M. OR 1990, 38, 225. (d) Yamamoto, Y. AG(E) 1986, 25, 947. (e) Erdik, E. T 1984, 40, 641. (f) Normant, J. F.; Alexakis, A. S 1981, 841. (g) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents; Wiley: New York, 1980. (h) Posner, G. H. OR 1975, 22, 253; 1972, 19, 1. (i) Burke, S. D.; Grieco, P. A. OR 1979, 26, 361.
2. Reich, M. R. CR(C) 1923, 177, 322 (CA 1924, 18, 383).
3. (a) Gilman, H.; Straley, J. M. RTC 1936, 55, 821. (b) Gilman, H.; Jones, R. G.; Woods, L. A. JOC 1952, 17, 1630.
4. (a) Bertz, S. H.; Smith, R. A. J. JACS 1989, 111, 8276. (b) Bertz, S. H.; Vellekoop, A. S.; Smith, R. A. J.; Snyder, J. P. OM 1995, in press.
5. Bertz, S. H.; Dabbagh, G. JACS 1988, 110, 3668.
6. Bertz, S. H.; Dabbagh, G. T 1989, 45, 425.
7. Bertz, S. H.; Gibson, C. P.; Dabbagh, G. TL 1987, 28, 4251.
8. (a) Bertz, S. H.; Gibson, C. P.; Dabbagh, G. OM 1988, 7, 227. (b) Bertz, S. H.; Dabbagh, G.; Mujsce, A. M. JACS 1991, 113, 631.
9. House, H. O.; Respess, W. L.; Whitesides, G. M. JOC 1966, 31, 3128.
10. House, H. O.; Fischer, W. F. Jr. JOC 1968, 33, 949.
11. Kharasch, M. S.; Tawney, P. O. JACS 1941, 63, 2308.
12. Corey, E. J.; Posner, G. H. JACS 1967, 89, 3911.
13. Corey, E. J.; Posner, G. H. JACS 1968, 90, 5615.
14. (a) Suzuki, M.; Suzuki, T.; Kawagishi, T.; Morita, Y.; Noyori, R. Isr. J. Chem. 1984, 24, 118. (b) Suzuki, M.; Suzuki, T.; Kawagishi, T.; Noyori, R. TL 1980, 21, 1247. (c) Suzuki, M.; Kawagishi, T.; Suzuki, T.; Noyori, R. TL 1982, 23, 4057. (d) Suzuki, M.; Yanagisawa, A.; Noyori, R. JACS 1988, 110, 4718.
15. (a) Bajgrowicz, J. A.; el Hallaoui, A.; Jacquier, R.; Pigiere, C.; Viallefont, P. T 1985, 41, 1833. (b) Spescha, M.; Rihs, G. HCA 1993, 76, 1219.
16. (a) Clark, R. D.; Heathcock, C. H. TL 1974, 15, 1713. (b) Corey, E. J.; Carney, R. L. JACS 1971, 93, 7318.
17. (a) Ibuka, T.; Nakao, T.; Nishii, S.; Yamamoto, Y. JACS 1986, 108, 7420. (b) Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Ishihara, Y.; Maruyama, K. JOC 1982, 47, 119. (c) Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Maruyama, K. JACS 1980, 102, 2318.
18. (a) Ghribi, A.; Alexakis, A.; Normant, J. F. TL 1984, 25, 3083. (b) Ito, Y.; Imai, H.; Matsuura, T.; Saegusa, T. TL 1984, 25, 3083. (c) Oppolzer, W.; Löher, H. J. HCA 1981, 64, 2808.
19. (a) Ibuka, T.; Tabushi, E. CC 1982, 703. (b) Ibuka, T.; Minakata, H.; Mitsui, Y.; Kinoshita, K.; Kawami, Y. CC 1980, 1193. (c) Ibuka, T.; Minakata, H.; Mitsui, Y.; Kinoshita, K.; Kawami, Y.; Kimura, N. TL 1980, 21, 4073.
20. Corey, E. J.; Boaz, N. W. TL 1985, 26, 6019.
21. Alexakis, A.; Berlan, J.; Besace, Y. TL 1986, 27, 1047.
22. Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.; Kuwajima, I. TL 1986, 27, 4029.
23. (a) Ebert, G. W.; Rieke, R. D. JOC 1984, 49, 5280. (b) Wehmeyer, R. M.; Rieke, R. D. TL 1988, 29, 4513.
24. Miyashita, A.; Yamamoto, A. BCJ 1977, 50, 1102.
25. Bertz, S. H.; Dabbagh, G.; He, X.; Power, P. P. JACS 1993, 115, 11640.
26. Normant, J. F.; Cahiez, G.; Bourgain, M.; Chuit, C.; Villieras, J. BSF(2) 1974, 1656.
27. Yamamoto, Y.; Yatagai, H.; Maruyama, K. JOC 1979, 44, 1744.
28. Saddler, J. C.; Fuchs, P. L. JACS 1981, 103, 2112.
29. Johnson, C. R.; Marren, T. J. TL 1987, 28, 27.
30. Bergdahl, M.; Lindstedt, E.-L.; Nilsson, M.; Olsson, T. T 1989, 45, 535.
31. Bertz, S. H.; Smith, R. A. J. T 1990, 46, 4091.
32. Schwartz, R. H.; San Filippo, J., Jr. JOC 1979, 44, 2705.
33. Posner, G. H.; Kogan, T. P.; Hulce, M. TL 1984, 25, 383.
34. Crimmins, M. T.; Mascarella, S. W.; DeLoach, J. A. JOC 1984, 49, 3033.
35. Meyers, A. I.; Pansegrau, P. D. CC 1985, 690.
36. Brockway, C.; Kocienski, P.; Pant, C. JCS(P1) 1984, 875.
37. Yunker, M. B.; Plaumann, D. E.; Fraser-Reid, B. CJC 1977, 55, 4002.
38. Rieke, R. D.; Stack, D. E.; Dawson, B. T.; Wu, T.-C. JOC 1993, 58, 2483.
39. Ebert, G. W.; Klein, W. R. JOC 1991, 56, 4744.
40. (a) Kitazume, T.; Ishikawa, N. CL 1982, 1453. (b) Luche, J. L.; Pétrier, C.; Gemal, A. L.; Zikra, N. JOC 1982, 47, 3805.
41. McMurry, J. E.; Scott, W. J. TL 1980, 21, 4313.
42. Clive, D. L. J.; Farina, V.; Beaulieu, P. L. JOC 1982, 47, 2572.
43. (a) Okuro, K.; Furuune, M.; Enna, M.; Miura, M.; Nomura, M. JOC 1993, 58, 4716. (b) Okuro, K.; Furuune, M.; Miura, M.; Nomura, M. JOC 1993, 58, 7606.
44. Corey, E. J.; Achiwa, K. TL 1970, 11, 2245.
45. Yates, P.; Fugger, J. CI(L) 1957, 1511.
46. House, H. O.; Fischer, W. F., Jr.; Gall, M.; McLaughlin, T. E.; Peet, N. P. JOC 1971, 36, 3429.

Steven H. Bertz & Edward H. Fairchild

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