Lithium Aluminum Hydride-Chromium(III) Chloride1


[16853-85-3]  · AlH4Li  · Lithium Aluminum Hydride-Chromium(III) Chloride  · (MW 37.96) (CrCl3)

[10025-73-7]  · Cl3Cr  · Lithium Aluminum Hydride-Chromium(III) Chloride  · (MW 158.35)

(reducing agent for reductive dimerization of allylic halides,2 halide reduction,2,3 and reductive alkylation of carbonyls2,4,5)

Physical Data: see Lithium Aluminum Hydride.

Solubility: sol THF, DMF, HMPA.

Form Supplied in: prepared in situ from commercially available compounds.

Preparative Method: by adding lithium aluminum hydride to anhydrous chromium(III) chloride suspended in THF at 0 °C under an argon atmosphere. A small amount of zinc metal helps solubilize the chromium(III) chloride. A 2:1 molar ratio of chromium(III) chloride to lithium aluminum hydride yields the most effective reagent.2

Handling, Storage, and Precautions: see Lithium Aluminum Hydride. Bottles of the lithium aluminum hydride-chromium(III) chloride reagent should be refrigerated and stored under argon.

Reductive Dimerization of Allylic Halides.

Chromium(II) Chloride is commercially available but expensive and susceptible to oxidation.6 One method of generating CrII ions in situ is through reduction of chromium(III) chloride with lithium aluminum hydride. Allylic and benzylic halides are reduced by this reagent to give mainly head-to-head coupling products (eq 1).2

Halide Reduction.

gem-Dibromocyclopropanes are reduced by the title reagent to give allenes (eq 2).2 Propargylic alkynes are also reduced to form allenes. Addition of HMPA favors allene formation over alkyne formation (eq 3).3 a-Bromo ketones are reduced to ketones (eq 4).2

Reductive Alkylation of Carbonyls.

Treatment of aldehydes and ketones with allylic halides in the presence of LiAlH4-CrCl3 gives carbonyl addition products (eq 5). Generally, the more substituted carbon of the allylic halide adds to the carbonyl carbon, affording homoallylic alcohols.7 Acetals, esters, and nitriles are not affected by the reagent and aryl, vinyl, and alkyl halides are not reduced. Aldehydes are more reactive than ketones, and 1,2-addition occurs with a,b-unsaturated carbonyls.2

Chiral a-substituted aldehydes frequently give low asymmetric induction, but in some cases, chiral allylic halides (eq 6)8 and chiral aldehydes (eq 7)9 have given excellent diastereoselectivity.10

Intramolecular addition of allylic halides to aldehydes is useful for large ring formation (eq 8).11

Treatment of aldehydes and ketones with propargyl bromide and LiAlH4-CrCl3 gives allenic alcohols (eq 9).5

Alkynyl halides have been coupled with aldehydes using LiAlH4-CrCl3. 1,2-Addition predominates with a,b-unsaturated aldehydes but ketones are unaffected (eq 10).4

Aldehydes have been coupled with 2-phenylsulfonyl allylic bromides to give mainly syn-homoallylic alcohols (eq 11).12

1. Cintas, P. S 1992, 248.
2. (a) Okude, Y.; Hirano, S.; Hiyama, T.; Nozaki, H. JACS 1977, 99, 3179. (b) Okude, Y.; Hiyama, T.; Nozaki, H. TL 1977, 18, 3829.
3. Delbecq, F.; Baudouy, R.; Gore, J. NJC 1979, 3, 321.
4. Takai, K.; Kuroda, T.; Nakatsukasa, S.; Oshima, K.; Nozaki, H. TL 1985, 26, 5585.
5. Place, P.; Delbecq, F.; Gore, J. TL 1978, 19, 3801.
6. Wuts, P. G. M.; Callen, G. R. SC 1986, 16, 1833.
7. Buse, C. T.; Heathcock, C. H. TL 1978, 19, 1685.
8. Hatakeyama, S.; Numata, H.; Osanai, K.; Takano, S. JOC 1989, 54, 3515.
9. Nagaoka, H.; Kishi, Y. T 1981, 37, 3873.
10. Mulzer, J.; Kattner, L.; Strecker, A. R.; Schroder, C.; Buschmann, J.; Lehmann, C.; Luger, P. JACS 1991, 113, 4218.
11. Kato, N.; Tanaka, S.; Takeshita, H. CL 1986, 1989.
12. Auvray, P.; Knochel, P.; Normant, J. F. TL 1986, 27, 5091.

Timothy A. Gillespy

The Ohio State University, Columbus, OH, USA

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