Chromium(II) Chloride

CrCl2

[10049-05-5]  · Cl2Cr  · Chromium(II) Chloride  · (MW 122.92)

(reducing agent for dehalogenation of organic halides, especially allylic and benzylic halides, and for transformation of carbon-carbon triple bonds leading to (E)-alkenes; conversion of dibromocyclopropanes to allenes; preparation and reaction of allylic chromium reagents; reduction of sulfur- or nitrogen-substituted alkyl halides to give hetero-substituted alkylchromium reagents)

Physical Data: mp 824 °C; d414 2.751 g cm-3.

Form Supplied in: off-white solid; commercially available.

Solubility: sol water, giving a blue solution; insol alcohol or ether.

Handling, Storage, and Precautions: very hygroscopic; oxidizes rapidly, especially under moist conditions; should be handled in a fume hood under an inert atmosphere (argon or nitrogen).

Reduction of Alkyl Halides.1,2

Typically, the chromium(II) ion is prepared by reduction of chromium(III) salts with zinc and hydrochloric acid. Organochromium compounds produced in this way can subsequently be hydrolyzed to yield dehalogenated compounds (eq 13 and eq 24). Anhydrous chromium(II) chloride is commercially available and can be used without further purification. The relative reactivities of various types of halide toward chromium(II) salts are shown in Scheme 1.

Conversion of Dihalocyclopropanes to Allenes.

Reduction of geminal dihalides proceeds smoothly to give chromium carbenoids.5 In the case of 1,1-dibromocyclopropanes, the intermediate carbenoids decompose instantaneously to give allenes (eq 3).6,7

Reductive Coupling of Allylic and Benzylic Halides.

Active halides, such as allyl and benzyl halides, are reduced with CrCl2 smoothly to furnish homocoupling products. Allylic halides undergo coupling, forming mainly the head-to-head dimer (eq 4).6,8

Formation of o-Quinodimethanes.

a,a-Dibromo-o-xylenes are reduced with CrCl2 in a mixed solvent of THF and HMPA to an o-quinodimethane, which can be trapped by a dienophile. The method has been applied to some anthracycline precursors (eq 5).9

Reduction of Carbon-Carbon Unsaturated Bonds.

The reduction of alkynes with chromium(II) salts in DMF leads to (E)-substituted alkenes.10 The ease of reduction depends on the presence of an accessible coordination site in the molecule (eq 6). Chromium(II) chloride in THF/H2O (2:1) (or Chromium(II) Sulfate in DMF/H2O) is effective at reducing a-alkynic ketones to (E)-enones. Less than 2% of (Z)-enones are produced except in the case of highly substituted substrates, which also require longer reaction times.11

Reduction of Other Functional Groups.

Deoxygenation of a,b-epoxy ketones proceeds with acidic solutions of CrCl2 to form a,b-unsaturated ketones.12 Chromium(II) chloride has been regularly used in the deoxygenation of the limonoid group of triterpenes, in which ring D bears an a,b-epoxy-d-lactone.13 Treatment of nitrobenzene derivatives with CrCl2 in methanol under reflux gives anilines (eq 7), while aliphatic nitro compounds afford aldehydes under the same reaction conditions.14 Reduction of a nitroalkene with acidic solutions of CrCl2 resulted in the formation of an a-hydroxy oxime.15

Preparation of Allylic Chromium Reagents.16

Allylic halides are reduced with low-valent chromium (CrCl3-LiAlH4) or CrCl2 to give the corresponding allylic chromium reagents, which add to aldehydes and ketones in good to excellent yields.17 The electronegativity of chromium is 1.6, almost the same as that of titanium (1.5). Therefore the nucleophilicity of organochromium reagents is not strong compared to the corresponding organolithium or -magnesium compounds. Chemoselective addition of allylic chromium reagents can be accomplished without affecting coexisting ketone and cyano groups (eq 8).17 The reaction between crotylchromium reagents and aldehydes in THF proceeds with high diastereoselectivity (eq 9).18,19 The anti (or threo) selectivity in the addition of acyclic allylic chromium reagents with aldehydes is explained by a chair-form six-membered transition state in which both R1 and R2 possess equatorial positions (1 > 2).

Addition of crotylchromium reagents to aldehydes bearing a stereogenic center a to the carbonyl provides three of the four diastereomers (eq 10).19 Excellent anti selectivity is observed with respect to the 1,2-positions, but the stereoselectivity with respect to the 2,3-positions (Cram/anti-Cram ratio) is poor.20-22 High 1,2- and 2,3-diastereoselectivity is obtained with aldehydes having large substituents, especially a cyclic acetal group, on the a-carbon of the aldehyde (eq 11).20,23 Reaction between chirally substituted acyclic allylic bromides and aldehydes proceeds with high stereocontrol (eq 12).24

As with allylic halides, allylic diethylphosphates25 and mesylates26,27 are reduced with chromium(II) salts to give allylic chromium reagents which add to aldehydes regio- and stereoselectively. This transformation reveals conversion of the electronic nature of allylic phosphates (or mesylates) from electrophilic to nucleophilic by reduction with low-valent chromium.

The reaction of g-disubstituted allylic phosphates with aldehydes mediated by CrCl2 and a catalytic amount of LiI in DMPU is not stereoconvergent and proceeds with high stereoselectivity (eqs 13 and 14).27 The presence of the two substituents at the g-position slows down the process of equilibration between the intermediate allylic chromium reagents.

Because the coupling reaction between allylic halides and aldehydes proceeds under mild conditions, the reaction has been employed, in particular, in intramolecular cyclizations.28-32 The intramolecular version also proceeds with high anti selectivity (eqs 15 and 16).

Functionalized and Hetero-Substituted Allylic Chromium Reagents.

When functionalized allylic halides are employed as precursors of allylic chromium reagents, an acyclic skeleton bearing a foothold for further construction is produced. Reaction of a-bromomethyl-a,b-unsaturated esters with aldehydes mediated by CrCl2 (or CrCl3-LiAlH4) affords homoallylic alcohols, which cyclize to yield a-methylene-g-lactones in a stereoselective manner (eq 17).33 Reaction between a-bromomethyl-a,b-unsaturated sulfonates and aldehydes also proceeds with high stereocontrol.34

The reaction of 3-alkyl-1,1-dichloro-2-propene with CrCl2 results in a-chloroalkylchromium reagents, which react with aldehydes to produce a 2-substituted anti-(Z)-4-chloro-3-buten-1-ol in a regio- and stereoselective manner (eq 18).35 Vinyl-substituted b-hydroxy carbanion synthons are produced by reduction of 1,3-diene monoepoxides with CrCl2 in the presence of LiI, which react stereoselectively with aldehydes to give (R*,R*)-1,3-diols having a quaternary center at C-2.36 Reduction in situ of acrolein dialkyl acetals with CrCl2 in THF provides g-alkoxy-substituted allylic chromium reagents which add to aldehydes at the same position of the alkoxy group to afford 3,4-butene-1,2-diol derivatives. The reaction rate and stereoselectivity are increased by addition of Iodotrimethylsilane (eq 19).37

Preparation of Propargylic Chromium Reagents.

Propargyl halides react with aldehydes or ketones in the presence of CrCl2 with HMPA as cosolvent to give allenes stereoselectively (eq 20).38 The reaction was modified to include polyfunctional propargylic halides by using CrCl2 and Lithium Iodide in DMA, and allenic alcohols accompanied only by small amounts of homopropargylic alcohols are produced.39

Sulfur- and Nitrogen-Stabilized Alkylchromium Reagents.

In combination with LiI, CrCl2 reduces a-halo sulfides to (a-alkylthio)chromium compounds, which undergo selective 1,2-addition to aldehydes. Acetophenone is recovered unchanged under the reaction conditions. The (1-phenylthio)ethenylchromium reagents prepared in this way add to aldehydes under high stereocontrol in the presence of suitable ligands like 1,2-diphenylphosphinoethane (dppe) (eq 21).40 The reaction of N-(chloromethyl)succinimide and -phthalimide with CrCl2 provides the corresponding a-nitrogen-substituted organochromium reagents in the presence of LiI. These organochromium reagents react in situ with aldehydes, affording protected amino alcohols (eq 22).41

Preparation of Alkylchromium Reagents.42

With the assistance of catalytic amounts of Vitamin B12 or cobalt phthalocyanine (CoPc), CrCl2 reduces alkyl halides, especially 1-iodoalkanes, to form alkylchromium reagents which add to aldehydes without affecting ketone or ester groups. The chemoselective preparation of organochromium reagents can be done by changing either the catalyst or the solvent. Alkenyl and alkyl halides remain unchanged under the conditions of the preparation of allylchromium reagents; on the other hand, alkenyl- and alkylchromium reagents are produced selectively under nickel and cobalt catalysis, respectively (eqs 23 and 24).

Related Reagents.

Chromium(II) Chloride-Haloform; Chromium(II) Chloride-Nickel(II) Chloride.


1. (a) Hanson, J. R.; Premuzic, E. AG(E) 1968, 7, 247; (b) Hanson, J. R. S 1974, 1.
2. (a) Castro, C. E.; Kray, W. C., Jr. JACS 1963, 85, 2768. (b) Kray, W. C., Jr.; Castro, C. E. JACS 1964, 86, 4603. (c) Kochi, J. K.; Singleton, D. M.; Andrews, L. J. T 1968, 24, 3503.
3. Traube, W.; Lange, W. CB 1925, 58, 2773.
4. Beereboom, J. J.; Djerassi, C.; Ginsburg, D.; Fieser, L. F. JACS 1953, 75, 3500.
5. Castro, C. E.; Kray, W. C., Jr. JACS 1966, 88, 4447.
6. Okude, Y.; Hiyama, T.; Nozaki, H. TL 1977, 3829.
7. Wolf, R.; Steckhan, E. J. Electroanal. Chem. 1981, 130, 367.
8. Sustmann, R.; Altevogt, R. TL 1981, 22, 5167.
9. Stephan, D.; Gorgues, A.; Le Coq, A. TL 1984, 25, 5649.
10. Castro, C. E.; Stephens, R. D. JACS 1964, 86, 4358.
11. Smith, A. B., III; Levenberg, P. A.; Suits, J. Z. S 1986, 184.
12. Cole, W.; Julian, P. L. JOC 1954, 19, 131.
13. (a) Arigoni, D.; Barton, D. H. R.; Corey, E. J.; Jeger, O.; Caglioti, L.; Dev, S.; Ferrini, P. G.; Glazier, E. R.; Melera, A.; Pradhan, S. K.; Slhaffner, K.; Sternhell, S.; Templeton, J. F.; Tobinaga, S. Experientia 1960, 16, 41. (b) Akisanya, A.; Bevan, C. W. L.; Halsall, T. G.; Powell, J. W.; Taylor, D. A. H. JCS 1961, 3705. (c) Ekong, D. E. U.; Olagbemi, O. E. JCS(C) 1966, 944.
14. Akita, Y.; Inaba, M.; Uchida, H.; Ohta, A. S 1977, 792.
15. (a) Hanson, J. R.; Premuzic, E. TL 1966, 5441; (b) Rao, T. S.; Mathur, H. H.; Trivedi, G. K. TL 1984, 25, 5561.
16. Cintas, P. S 1992, 248.
17. (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. JACS 1977, 99, 3179. (b) Hiyama, T.; Okude, Y.; Kimura, K.; Nozaki, H. BCJ 1982, 55, 561.
18. Buse, C. T.; Heathcock, C. H. TL 1978, 1685.
19. Hiyama, T.; Kimura, K.; Nozaki, H. TL 1981, 22, 1037.
20. (a) Nagaoka, H.; Kishi, Y. T 1981, 37, 3873. (b) Lewis, M. D.; Kishi, Y. TL 1982, 23, 2343.
21. Fronza, G.; Fganti, C.; Grasselli, P.; Pedrocchi-Fantoni, G.; Zirotti, C. CL 1984, 335.
22. Evans, D. A.; Dow, R. L.; Shih, T. L.; Takacs, J. M.; Zahler, R. JACS 1990, 112, 5290.
23. Roush, W. R.; Palkowitz, A. D. JOC 1989, 54, 3009.
24. (a) Mulzer, J.; de Lasalle, P.; Freißler, A. LA 1986, 1152. (b) Mulzer, J.; Kattner, L. AG(E) 1990, 29, 679. (c) Mulzer, J.; Kattner, L.; Strecker, A. R.; Schröder, C.; Buschmann, J.; Lehmann, C.; Luger, P. JACS 1991, 113, 4218.
25. Takai, K.; Utimoto, K. J. Synth. Org. Chem. Jpn. 1988, 46, 66.
26. Kato, N.; Tanaka, S.; Takeshita, H. BCJ 1988, 61, 3231.
27. Jubert, C.; Nowotny, S.; Kornemann, D.; Antes, I.; Tucker, C. E.; Knochel, P. JOC 1992, 57, 6384.
28. Still, W. C.; Mobilio, D. JOC 1983, 48, 4785.
29. Shibuya, H.; Ohashi, K.; Kawashima, K.; Hori, K.; Murakami, N.; Kitagawa, I. CL 1986, 85.
30. Kato, N.; Tanaka, S.; Takeshita, H. CL 1986, 1989.
31. Wender, P. A.; McKinney, J. A.; Mukai, C. JACS 1990, 112, 5369.
32. (a) Paquette, L. A.; Doherty, A. M.; Rayner, C. M. JACS 1992, 114, 3910. (b) Rayner, C. M.; Astles, P. C.; Paquette, L. A. JACS 1992, 114, 3926. (c) Paquette, L. A.; Astles, P. C. JOC 1993, 58, 165.
33. (a) Okuda, Y.; Nakatsukasa, S.; Oshima, Y.; Nozaki, H. CL 1985, 481. (b) Drewes, S. E.; Hoole, R. F. A. SC 1985, 15, 1067.
34. (a) Auvray, P.; Knochel, P.; Normant, J. F. TL 1986, 27, 5091. (b) Auvray, P.; Knochel, P.; Vaissermann, J.; Normant, J. F. BSF 1990, 127, 813.
35. (a) Takai, K.; Kataoka, Y.; Utimoto, K. TL 1989, 30, 4389. (b) Wender, P. A.; Grissom, J. W.; Hoffmann, U.; Mah, R. TL 1990, 31, 6605. (c) Augé, J. TL 1988, 29, 6107.
36. Fujimura, O.; Takai, K.; Utimoto, K. JOC 1990, 55, 1705.
37. (a) Takai, K.; Nitta, K.; Utimoto, K. TL 1988, 29, 5263. (b) Roush, W. R.; Bannister, T. D. TL 1992, 33, 3587.
38. (a) Place, P.; Delbecq, F.; Gore, J. TL 1978, 3801. (b) Place, P.; Venière, C.; Gore, J. T 1981, 37, 1359.
39. Belyk, K.; Rozema, M. J.; Knochel, P. JOC 1992, 57, 4070.
40. Nakatsukasa, S.; Takai, K.; Utimoto, K. JOC 1986, 51, 5045.
41. Knochel, P.; Chou, T.-S.; Jubert, C.; Rajagopal, D. JOC 1993, 58, 588.
42. Takai, K.; Nitta, K.; Fujimura, O.; Utimoto, K. JOC 1989, 54, 4732.

Kazuhiko Takai

Okayama University, Japan



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.