Chromium(II) Chloride-Nickel(II) Chloride


[10049-05-5]  · Cl2Cr  · Chromium(II) Chloride-Nickel(II) Chloride  · (MW 122.92) (NiCl2)

[7718-54-9]  · Cl2Ni  · Chromium(II) Chloride-Nickel(II) Chloride  · (MW 129.61)

(catalyst for coupling reactions between haloalkenes (or alkenyl triflates) and aldehydes; active low-valent nickel catalyst)

Physical Data: see entries for Chromium(II) Chloride and Nickel(II) Chloride.

Preparative Method: a mixture of anhyd CrCl2 (0.47 g, 4.0 mmol) and a catalytic amount of NiCl2 (2.6 mg, 0.020 mmol) in dry, oxygen-free DMF (10 mL) is stirred at 25 °C for 10 min under Ar; add successively a solution of an aldehyde (1.0 mmol) in DMF (5 mL) and a solution of a haloalkene (or an alkenyl triflate; 2.0 mmol) in DMF (5 mL) and stir at 25 °C for 1 h, dilute the reaction mixture with ether (20 mL), pour into water (20 mL), and extract with ether repeatedly; dry the combined extracts over Na2SO4 and concentrate; purification by column chromatography gives an allylic alcohol; DMSO or a DMF/THF mixture may be used as solvent (ether and THF are unsuitable).

Handling, Storage, and Precautions: chromium(II) chloride should be used in a fume hood under an inert atmosphere (argon or nitrogen).

Grignard-Type Carbonyl Addition of Haloalkenes to Aldehydes.1-3

The carbonyl addition reaction mediated by CrCl2 was first reported without any catalyst.4 Later, a catalytic amount of nickel proved to be indispensable to promote the Grignard-type carbonyl addition of haloalkenes to aldehydes with good reproducibility (eq 1).1,2 It is important to keep the content of NiCl2 in CrCl2 low (about 0.01-1% w/w) to avoid formation of dienes by homocoupling of the haloalkenes.5 The Grignard-type reaction between alkenyl triflates and aldehydes proceeds under the same conditions.1 In the case of a,b-unsaturated aldehydes, 1,2-addition products are the major products.

The process has many advantages. The basicity of the formed alkenylchromium reagent is not high, and epimerization at the a-position of aldehydes therefore generally does not take place. The regiochemistry of double bonds is maintained during the coupling reaction (eq 2).6 Mild nucleophilicity of the alkenylchromium reagents permits addition to aldehydes in good to excellent yields without affecting coexisting ketone, ester, amide, acetal, silyl ether, cyano, and sulfinyl groups.1 -4,6 -9 The system is especially effective for coupling reactions of highly oxygenated multifunctional substrates.2,3,7 The stereochemistry of trans- and cis-haloalkenes is retained, at least in the case of disubstituted haloalkenes and trisubstituted trans-haloalkenes (eqs 3 and 4).1,2 Treatment of a trisubstituted cis-haloalkene (or an alkenyl triflate) with the CrCl2-NiCl2 system often results in a cis-trans isomerization-coupling reaction sequence or in recovery of the starting alkenyl halide. With respect to the newly introduced stereogenic center, the process produces a mixture of two possible diastereomers with a moderate to good preference for one stereoisomer. The major products produced from a-alkoxy- and a,b-bisalkoxyaldehydes have the stereochemistry opposite to cuprate or Grignard products.2

Intramolecular cyclization using the reagent proceeds under mild conditions (eqs 5 and 6).8,9

Grignard-Type Carbonyl Addition of Haloalkynes to Aldehydes.

Although reactions between simple haloalkynes and aldehydes proceed in the absence of NiCl2, the CrCl2-NiCl2 system is employed in the case of highly-oxygenated substrates (eq 7)10,11 and for intramolecular cyclizations (eq 8).12,13 The process is exceptionally well suited for cases where the aldehyde is labile.

Active Low-Valent Nickel Catalyst.

Intramolecular cyclization of enynes14 and enallenes15 proceeds with a catalytic amount of low-valent nickel derived by reduction of NiCl2 with CrCl2 in the presence of triphenylphosphine (eq 9). Decrease of catalytic activity of the nickel is suppressed by using a polymer-supported nickel catalyst.

1. Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. JACS 1986, 108, 6048.
2. Jin, H.; Uenishi, J.; Christ, W. J.; Kishi, Y. JACS 1986, 108, 5644.
3. Kishi, Y. PAC 1992, 64, 343.
4. Takai, K.; Kimura, K.; Kuroda, T.; Hiyama, T.; Nozaki, H. TL 1983, 24, 5281.
5. Zembayashi, M.; Tamao, K.; Yoshida, J.; Kumada, M. TL 1977, 4089.
6. Chen, S.-H.; Horvath, R. F.; Joglar, J.; Fisher, M. J.; Danishefsky, S. J. JOC 1991, 56, 5834.
7. (a) Aicher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C. J.; Jung, S. H.; Kishi, Y.; Matelich, M. C.; Scola, P. M.; Spero, D. M.; Yoon, S. K. JACS 1992, 114, 3162. (b) Aicher, T. D.; Buszek, K. R.; Fang, F. G.; Forsyth, C. J.; Jung, S. H.; Kishi, Y.; Scola, P. M. TL 1992, 33, 1549.
8. Schreiber, S. L.; Meyers, H. V. JACS 1988, 110, 5198.
9. (a) Rowley, M.; Kishi, Y. TL 1988, 29, 4909. (b) Rowley, M.; Tsukamoto, M.; Kishi, Y. JACS 1989, 111, 2735.
10. Aicher, T. D.; Kishi, Y. TL 1987, 28, 3463.
11. Wang, Y.; Babirad, S. A.; Kishi, Y. JOC 1992, 57, 468.
12. Crévisy, C.; Beau, J.-M. TL 1991, 32, 3171.
13. Nicolaou, K. C.; Liu, A.; Zeng, Z.; McComb, S. JACS 1992, 114, 9279.
14. Trost, B. M.; Tour, J. M. JACS 1987, 109, 5268.
15. Trost, B. M.; Tour, J. M. JACS 1988, 110, 5231.

Kazuhiko Takai

Okayama University, Japan

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