NICKEL 1
Nickel
NiI2, , Li
CH2Cl
glyme, 70 °C, 0.5 h
Ni0 86%
(3)
[7440-02-0] Ni (MW 58.71)
InChI = 1/Ni
InChIKey = PXHVJJICTQNCMI-UHFFFAOYAH
NiI2, , Li
(homocoupling of halobenzenes;1,2 benzyl halide coupling;3,4
CCl3 glyme, 85 °C, 1 h
synthesis of ²-hydroxynitriles;5 xylylene cycloadditions;6
71%
synthesis of 3-arylpropanenitriles7)
Form Supplied in: black powder; activated nickel is not commer-
Cl Cl Cl
cially available and must be prepared prior to use.
+ (4)
Preparative Methods: activated nickel is prepared by the reduc-
Cl
tion of nickel iodide with Lithium metal under argon with a
catalytic amount of naphthalene in glyme.6
74% cis 26% trans
Handling, Storage, and Precautions: all reactions should be car-
ried out in an inert atmosphere. Appropriate precautions are
necessary since the reagent is a cancer suspect agent. Use in a
Coupling of Benzyl Halides. Metallic nickel is a convenient
fume hood.
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.
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
O NiI2, , Li
results are obtained with unsubstituted or 4-substituted iodoben-
+
CH2Cl
glyme, 85 °C, 15 min
Cl
zenes. Ortho substitutents, particularly nitro groups, seem to in-
86%
hibit 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
(5)
DMF have all been used as solvents with very little difference in
O
yields.
²
Synthesis of ²
²-Hydroxynitriles. Metallic nickel can effect
NiI2, , Li
Reformatsky-type addition of haloacetonitriles to aldehydes at
MeO I
glyme, 80 °C, 2 h
ć%
85 C in glyme to give ²-hydroxynitriles (eq 6).5 Bromoacetoni-
85%
triles give the best results, but chloro- and iodoacetonitriles also
react.
MeO OMe (1)
NiI2, , Li
+ BrCH2CN
CHO
glyme, 85 °C
84%
NiI2, , Li
Cl Br
glyme, 85 °C, 20 h
61% OH
(6)
(2) CH2CN
Cl Cl
The use of activated nickel powder is superior to the Ullmann Cycloadditions of o-Xylylenes with Dienophiles. Acti-
ć%
synthesis in that reaction temperatures are much milder (80 C vated nickel reacts with Ä…,Ä… -dihalo-o-xylene in the presence of
ć%
compared to 150 280 C) and yields are generally better. electron-deficient alkenes to yield 1,2,3,4-tetrahydronaphthalene
Unsubstituted and monosubstituted benzylic halides react with derivatives in moderate yield (eq 7).6 This reaction proceeds, pre-
metallic nickel at room temperature to afford the correspond- sumably, via an o-xylylene intermediate. A variety of alkenes give
ing 1,2-diarylethanes in good yield (eq 3).2 Substituents such the expected cycloaddition products. In general, cis-alkenes yield
as methoxy, chloro, bromo, nitro, cyano, and alkoxycarbonyl a mixture of cis and trans products (eq 8), while trans-alkenes
groups are well tolerated. Reactions of benzylic di- and trihalides only give trans products (eq 9).6 Although the cycloaddition
gives mixtures of cis- and trans-ethylenes (eq 4).2 has not been proven to be either concerted or stepwise, the
Avoid Skin Contact with All Reagents
2 NICKEL
mixtures of cis and trans products can be explained by isomeri- 3-arylpropanenitriles (eq 10).7 The reaction conditions are com-
zation of the alkenes prior to the cycloaddition. patible with a variety of substituents including halogens, nitriles,
and alkoxycarbonyl groups (eqs 11 and 12).
CO2Me
Ni, DME
Ni, glyme
Br
+ BrCH2CN (10)
Br 67%
85 °C
rt
Cl CN
57%
Br
Ni, glyme
CO2Me
+ BrCH2CN
(7) 85 °C
Cl
43%
NC
CO2Et
(11)
CN
CO2Et
Br Ni, DME
Br rt 67% Cl O
Ni, glyme
+ BrCH2CN
85 °C
OMe
55%
CO2Et
(8)
MeO
(12)
CO2Et
O CN
cis:trans = 1:1
CO2Et
1. Matsumoto, H.; Inaba, S.; Rieke, R. D., J. Org. Chem. 1983, 48, 840.
EtO2C
Br Ni, DME
2. Inaba, S.; Matsumoto, H.; Rieke, R. D., J. Org. Chem. 1984, 49, 2093.
Br rt 76%
3. Inaba, S.; Matsumoto, H.; Rieke, R. D., Tetrahedron Lett. 1982, 23, 4215.
4. Inaba, S.; Rieke, R. D., Tetrahedron Lett. 1983, 24, 2451.
5. Inaba, S.; Rieke, R. D., Tetrahedron Lett. 1985, 26, 155.
CO2Et
6. Inaba, S.; Wehmeyer, R. M.; Forkner, M. W.; Rieke, R. D., J. Org. Chem.
(9)
1988, 53, 339.
CO2Et
7. Inaba, S.; Rieke, R. D., Synthesis 1984, 842.
Ellen M. Leahy
Preparation of 3-Arylpropanenitriles. Benzylic halides
Affymax Research Institute, Palo Alto, CA, USA
react with haloacetonitriles in the presence of nickel to form
A list of General Abbreviations appears on the front Endpapers