Lithium Aluminum Hydride-Nickel(II) Chloride1


[16853-85-3]  · AlH4Li  · Lithium Aluminum Hydride-Nickel(II) Chloride  · (MW 37.96) (NiCl2)

[7718-54-9]  · Cl2Ni  · Lithium Aluminum Hydride-Nickel(II) Chloride  · (MW 129.59)

(reducing agent for alkenes, alkynes,2,3 and organic halides;2,4 can effect N-O bond cleavage and open epoxides.5)

Physical Data: see Lithium Aluminum Hydride and Nickel(II) Chloride.

Solubility: see Lithium Aluminum Hydride and Nickel(II) Chloride; reactions using the mixture are run in THF.

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

Preparative Method: nickel(II) chloride (1 equiv for stoichiometric reactions and 0.1 equiv for catalytic reactions) is placed in the reaction vessel at -40 °C and the organic substrate (1 equiv) in THF is added using a syringe. Lithium aluminum hydride (1 equiv) in THF is added slowly, resulting in a black color and gas evolution.

Handling, Storage, and Precautions: see Lithium Aluminum Hydride and Nickel(II) Chloride.

Halide Reductions.

Reductions of organic halides using lithium aluminum hydride and nickel(II) chloride are more efficient than reductions using lithium aluminum hydride alone.2,4 This mixed reagent converts primary chlorides, bromides, iodides, and tosylates into the corresponding alkanes in near quantitative yields using only a catalytic amount of the nickel species (eq 1). High yields are also realized using stoichiometric amounts of metal halide in the reduction of secondary, tertiary, and aryl chlorides, bromides, and iodides (eqs 2 and 3). These reductions may also be carried out with similar results using Iron(II) Chloride, Cobalt(II) Chloride, or Titanium(III) Chloride as the metal halide.

Furthermore, triarylvinyl halides can be reduced to the corresponding hydrocarbons using LiAlH4-NiCl2 at temperatures below 0 °C (eq 4).6

The strong reducing nature of this reagent has limited its use in synthesis, as many other functional groups do not survive the conditions. For example, esters are reduced faster than tertiary halides (eq 7).7

Reduction of Carbon-Carbon Double and Triple Bonds.

The admixture of lithium aluminum hydride-nickel(II) chloride has been used to efficiently reduce alkenes to the corresponding alkanes and to effect the partial reduction of an alkyne to an alkene.2,3 Such transformations require only catalytic amounts of the nickel species for monosubstituted alkenes or alkynes, but higher orders of substitution require stoichiometric amounts of nickel(II) chloride (eqs 6-8). Cobalt(II) chloride works equally well when used as the metal halide species for these reductions.

This mixed reagent has been used to reduce alkenes in the presence of ethers and acetals (eq 9),8 but fails to selectively reduce triple bonds in the presence of esters.9

Cleavage of N-O Bonds and Epoxide Opening.

Amino alcohols have been prepared in high yield from isoxazolidines with LiAlH4-NiCl2 (eq 10). This mixed reagent has also been used to open epoxides to alcohols.5 This admixture reacts with styrene oxide to yield b-phenylethanol (eq 11). In contrast, use of lithium aluminum hydride alone gives a-phenylethanol.

Reduction of an N-O bond with lithium aluminum hydride-nickel(II) chloride has been used in an approach to anatoxin a (eq 12).5 Initial N-O bond cleavage gives an epoxide which is opened by the reducing agent to give an alcohol.

1. Ganem, B.; Osby, J. O. CRV 1986, 86, 763.
2. Ashby, E. C.; Lin, J. J. TL 1977, 4481.
3. Ashby, E. C.; Lin, J. J. JOC 1978, 43, 2567.
4. Ashby, E. C.; Lin, J. J. JOC 1978, 43, 1263.
5. Tufariello, J. J.; Meckler, H.; Senaratne, K. P. A. T 1985, 41, 3447.
6. Obafemi, C. A.; Lee, C. C. CJC 1990, 68, 1998.
7. Rao, V. B.; Wolff, S.; Agosta, W. C. T 1986, 42, 1549.
8. Kochetkvo, N. K.; Sviridov, A. F.; Ermolenko, M. S. TL 1981, 22, 4319.
9. Eilbracht, P.; Huttmann, G.-E. CB 1990, 123, 1053.

Brian B. Filippini

The Ohio State University, Columbus, OH, USA

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