[7440-02-0]  · Ni  · Nickel  · (MW 58.71)

(homocoupling of halobenzenes;1,2 benzyl halide coupling;3,4 synthesis of b-hydroxynitriles;5 xylylene cycloadditions;6 synthesis of 3-arylpropanenitriles7)

Form Supplied in: black powder; activated nickel is not commercially available and must be prepared prior to use.

Preparative Methods: activated nickel is prepared by the reduction of nickel iodide with Lithium metal under argon with a catalytic amount of naphthalene in glyme.6

Handling, Storage, and Precautions: all reactions should be carried out in an inert atmosphere. Appropriate precautions are necessary since the reagent is a cancer suspect agent. Use in a fume hood.

Homocoupling Reactions of Halobenzenes.

Activated metallic nickel powder is a simple and convenient reagent for coupling iodobenzenes and bromobenzenes (eqs 1 and 2).1 Best results are obtained with unsubstituted or 4-substituted iodobenzenes. Ortho substitutents, particularly nitro groups, seem to inhibit coupling. Electron-donating substitutents seem to lower the reactivity. Carbonyl groups and nitriles are compatible and afford good yields of the corresponding biphenyls. Glyme, DMSO, and DMF have all been used as solvents with very little difference in yields.

The use of activated nickel powder is superior to the Ullmann synthesis in that reaction temperatures are much milder (80 °C compared to 150-280 °C) and yields are generally better.

Unsubstituted and monosubstituted benzylic halides react with metallic nickel at room temperature to afford the corresponding 1,2-diarylethanes in good yield (eq 3).2 Substituents such as methoxy, chloro, bromo, nitro, cyano, and alkoxycarbonyl groups are well tolerated. Reactions of benzylic di- and trihalides gives mixtures of cis- and trans-ethylenes (eq 4).2

Coupling of Benzyl Halides.

Metallic nickel is a convenient reagent for the reductive coupling of benzyl halides with acyl halides to afford benzyl ketones (eq 5).4 Best results are obtained in refluxing glyme, although some reactions proceed even at room temperature.

Synthesis of b-Hydroxynitriles.

Metallic nickel can effect Reformatsky-type addition of haloacetonitriles to aldehydes at 85 °C in glyme to give b-hydroxynitriles (eq 6).5 Bromoacetonitriles give the best results, but chloro- and iodoacetonitriles also react.

Cycloadditions of o-Xylylenes with Dienophiles.

Activated nickel reacts with a,a-dihalo-o-xylene in the presence of electron-deficient alkenes to yield 1,2,3,4-tetrahydronaphthalene derivatives in moderate yield (eq 7).6 This reaction proceeds, presumably, via an o-xylylene intermediate. A variety of alkenes give the expected cycloaddition products. In general, cis-alkenes yield a mixture of cis and trans products (eq 8), while trans-alkenes only give trans products (eq 9).6 Although the cycloaddition has not been proven to be either concerted or stepwise, the mixtures of cis and trans products can be explained by isomerization of the alkenes prior to the cycloaddition.

Preparation of 3-Arylpropanenitriles.

Benzylic halides react with haloacetonitriles in the presence of nickel to form 3-arylpropanenitriles (eq 10).7 The reaction conditions are compatible with a variety of substituents including halogens, nitriles, and alkoxycarbonyl groups (eqs 11 and 12).

1. Matsumoto, H.; Inaba, S.; Rieke, R. D. JOC 1983, 48, 840.
2. Inaba, S.; Matsumoto, H.; Rieke, R. D. JOC 1984, 49, 2093.
3. Inaba, S.; Matsumoto, H.; Rieke, R. D. TL 1982, 23, 4215.
4. Inaba, S.; Rieke, R. D. TL 1983, 24, 2451.
5. Inaba, S.; Rieke, R. D. TL 1985, 26, 155.
6. Inaba, S.; Wehmeyer, R. M.; Forkner, M. W.; Rieke, R. D. JOC 1988, 53, 339.
7. Inaba, S.; Rieke, R. D. S 1984, 842.

Ellen M. Leahy

Affymax Research Institute, Palo Alto, CA, USA

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