NICKEL-IN-CHARCOAL

1

Nickel-in-Charcoal

Ni

II

/C

[7440-02-0]

Ni

II

/C

InChI = 1/C.Ni/q;+2
InChIKey = GAYXURBANYOVBS-UHFFFAOYAX

(a heterogeneous catalyst that has been applied to a number of

group 10 transition metal mediated cross-coupling reactions)

Form Supplied in:

not a commercially available substance.

Preparative Methods:

Ni/C can be prepared using the follow-

ing procedure.

3

Darco

R

KB (5.00 g, 100 mesh) activated car-

bon (25% H

2

O content) was added to a 100 ml round-bottom

flask along with a stir bar. A solution of Ni(NO

3

)

2

·

6H

2

O

(727 mg, Aldrich, 24,407-4, Ni content by ICP determination:
92% of reagent purity; 2.30 mmol) in deionized H

2

O (35 ml)

was added to the activated carbon and more deionized H

2

O

(40 ml) was added to wash down the sides of the flask. The
flask was purged under argon and stirred vigorously for 1 min.
The flask was submerged in an ultrasonication bath under a
positive argon flow for 30 min. The flask was then attached
to an argon purged distillation setup and placed in a preheated
175–180

◦

C sand bath atop a stir plate. As the distillation ended,

the sand bath temperature increased automatically but was held
below 210

◦

C for an additional 15 min. Upon cooling to room

temperature, the black solid was washed with H

2

O (2 × 50 ml)

under argon into a predried 150 ml coarse fritted funnel
(Figure 1). The H

2

O (100 ml) used to wash the Ni/C was

rotary evaporated and analyzed for

recovered

nickel

(ICP). The fritted funnel was turned upside down under vac-

Figure 1

Glassware for filtration and drying of Ni/C

uum for 3 h until the Ni/C fell from the frit into the collection
flask. The collection flask was then dried in vacuo at 100

◦

C

for 18 h. Using these specific amounts, all of the nickel was
mounted in the support, which corresponds to 0.552 mmol
Ni

II

/g catalyst, or 3.2% Ni/catalyst by weight. To achieve very

dry catalyst, two 50 ml portions of toluene can be distilled from
wet Ni/C following the H

2

O distillation to azeotropically dry

the reagent.

Handling, Storage, and Precautions:

Ni/C is generally an air and

moisture stable solid. However, due the sensitivity of some of
the chemistry in which it can be used (e.g, Negishi couplings),
Ni/C is stored in a glass bottle within a dry, inert atmosphere.
Under these conditions, the lifetime of the catalyst is expected
to be several months.

Suzuki Couplings of Aryl Chlorides.

4

A variety of function-

alized arylboronic acids and aryl chlorides (either partner being
substituted by activating or deactivating substituents) can be cou-
pled to produce biaryl products in good to excellent yields (eq 1).
The active Ni

0

complex is preformed by treating a Ni/C + Ph

3

P

mixture in dioxane with n-BuLi under an inert atmosphere, at
room temperature. Amounts of Ni/C as low as 2% relative to sub-
strate are sufficient to mediate Suzuki couplings. Nonetheless, un-
like precious metal-based catalysis, the amount of this base metal
required is actually of no consequence, as it is of minimal cost
and easily recoverable. The reaction is refluxed and monitored
for the disappearance of aryl chloride. Solvent studies have sug-
gested dry, deoxygenated 1,4-dioxane to be the ideal medium for
the catalysis. When complete, the reaction can be filtered through
a pad of Celite

R

to remove insoluble catalyst and the products

are purified by standard column chromatography. Results on the
majority of cases are competitive with those obtained under simi-
lar but homogeneous conditions.

5

B

HO

OH

N

Cl

MeO

N

MeO

Ni/C, Ph

3

P, K

3

PO

4

+

85%

(1)

LiBr, dioxane, ∆

Activated aryl chlorides can be coupled with substituted boronic

acids in as little as 35 min using microwave irradiation (eq 2).

6,7

Electron-rich chlorides, however, do not yield consistent and
reproducible results. Instead, successful Suzuki biaryls are to be
expected for this class of aromatic substrates using the equivalent
aryl bromide. These couplings are assisted by KF, suggesting the
possibility of a reactive potassium fluoroborate intermediate.

8,9

Although not fully investigated, couplings are likely to be general
as well between aryl boronic acids and the heavier aryl halides
(Br, I) using heterogeneous Ni/C.

Avoid Skin Contact with All Reagents

2

NICKEL-IN-CHARCOAL

NC

Cl

B

O

O

HO

OH

NC

O

O

dioxane, µW, 200

°C, 35 min

+

81%

(2)

Ni/C, Ph

3

P, KF, LiOH

Aromatic Aminations.

10

,

11

Ni/C also allows for a wide

variety of functionalized aryl halides, most notably aryl chlo-
rides, to be converted into their anilino derivatives (eq 3). The
catalyst, which is likely to be Ni

II

oxide, is most effective to-

ward aminations following prereduction to the Ni

0

species with

n

-BuLi. Aminations do proceed without the n-BuLi treatment, as

amines are known to mediate electron transfer to Ni

II

.

12

However,

the induction period for reduction produces a marked decrease in
overall reaction rate when the nickel is not first forcibly converted
to its active Ni

0

oxidation state. Both activated and deactivated,

functionalized aryl chlorides, including sterically hindered ortho-
substituted cases, react favorably in refluxing toluene with pri-
mary and secondary amines with a catalyst level of 10%. From a
thorough ligand study, dppf was found to be the ligand of choice.
Isolated yields tend to be good to modest, ranging from 70 to 93%,
with reaction times as short as 2.5 h. However, as the reaction rate
is substrate dependent, other aminations can take as long as 48 h.
Upon completion, the catalyst can be filtered and reused with no
loss of activity.

O

Cl

HN

O

N

Ni/C, dppf, LiO-t-Bu

+

87%

(3)

toluene, ∆, 16 h

Microwave irradiation at ca. 200

◦

C has been shown, as

expected, to enhance reaction rates, leading to complete con-
version in under 1 h (eq 4).

7

Electron-rich chlorides require the

longest reactions times; however, activated cases of chlorides, bro-
mides, and iodides reach full conversion in only 10–15 min when
irradiated under controlled conditions.

Cl

OMe

HN

O

N

O

MeO

Ni/C, dppf, LiO-t-Bu

86%

+

(4)

dioxane, µW, 200

°C, 40 min

Kumada Couplings.

10

,

13

A variety of electron-rich aryl chlo-

rides can be efficiently coupled with both alkyl and aryl Grig-
nard reagents under the influence of Ni/C. Benzylic reagents are
especially amenable to transmetallation, affording unsymmetrical
diarylmethanes in as little as 9 h (eq 5). Other aliphatic and aro-
matic reagents require slightly longer reaction times (10–20 h).
In general, as with most nickel-catalyzed cross-couplings, the
active oxidation state of metal must be Ni

0

, typically achieved

by addition of 2 equiv of n-BuLi. However, this oxidation state
can be more conveniently reached by simply employing an
excess of the Grignard species in the flask. Thus, by adding RMgX
(1.4–1.7 equiv versus substrate) to the 5% Ni

II

/C dispersed in THF

in the presence of 20 mol % Ph

3

P at room temperature, Ni

0

/C is

generated in situ within minutes.

Cl

F

OMe

MgCl

OMe

F

+

Ni/C, Ph

3

P, LiBr

78%

(5)

THF, ∆, 9 h

The extent of functional-group tolerance in this methodology is

governed by the highly basic and nucleophilic character of Grig-
nard reagents, and hence, an electrophilic center present in the
adduct is not typically tolerated. More recent studies have shown
that Kumada couplings can be carried out at ambient tempera-
tures.

14,15

Unfortunately, attempts to mimic these temperature

conditions using Ni/C have so far met with little success.

Negishi Couplings.

16

Negishi’s original description of

Pd- and Ni-catalyzed couplings focused on vinylzirconocenes,

17

which are prepared by traditional hydrozirconations of terminal
acetylenes. The use of transmetallation-derived organozinc com-
plexes (RZnX) has come to be better known as Negishi couplings,
and can be successfully affected by Ni/C using functionalized aryl
chlorides as reaction partners.

18

A variety of organozinc halides

readily undergo coupling in refluxing THF with aryl chlorides
bearing ketones, esters, nitriles, aldehydes, etc. Particularly note-
worthy is an example involving a diaryl sulfide (eq 6). Good
to excellent yields of the cross-coupled products are commonly
observed.

S

O

Cl

IZn

CN

S

O

CN

Ni/C, Ph

3

P, LiCl

+

72%

(6)

THF, ∆, 20 h

As conventional heating of the heterogeneous mixtures can

lead to elongated reaction times, microwave irradiation has been
found to greatly accelerate these couplings.

7

Advantageously, this

method negates prior n-BuLi-mediated reduction of the Ni

II

/C

A list of General Abbreviations appears on the front Endpapers

NICKEL-IN-CHARCOAL

3

catalyst. Complete in as little as 15 min, the couplings involving
arylzinc halides retain high efficiencies and substrate compati-
bility. Selected Negishi couplings of alkylzinc halides are limited
due to decomposition of starting material at temperatures >70

◦

C.

Nonetheless, high yielding reactions can still be effected in as
little as 30 min under these restricted conditions (eq 7).

NC

Cl

IZn

O

OEt

NC

O

OEt

Ni/C, Ph

3

P, dioxane/THF

+

85%

(7)

µW, 70

°C, 30 min

More traditional Negishi coupling partners (vinyl zirconocenes

and aryl chlorides) are also susceptible to Ni/C-catalyzed cou-
pling. Initially accomplished in refluxing THF, the Ni/C-catalyzed
Negishi coupling of an activated aryl iodide and a vinyl zir-
conocene required up to 24 h to reach a modest 70% conver-
sion. However, the reaction is markedly accelerated by microwave
assistance. At ca. 200

◦

C in a sealed tube under microwave irra-

diation, the catalyst effects the complete conversion in 10 min
(eq 8).

7

Chlorides require 30–40 min, while aryl bromides need

only 15–20 min. Unfortunately, related substrates including aryl
nonaflates, vinyl iodides, and benzylic chlorides led to limited suc-
cess, giving incomplete reactions that included multiple uniden-
tifiable side products.

F

3

C

I

ClCp

2

Zr

C

6

H

13

-n

F

3

C

C

6

H

13

-n

Ni/C, THF, ∆, 24 h

Ni/C, THF

70% conversion

95% isolated yield

+

(8)

µW, 200

°C, 10 min

A fairly thorough ligand query was carried out which high-

lighted Ph

3

P as the most effective (and least costly) ligand for this

transformation. Less-effective ligands include Cy

3

P, dppe, dppf,

and (±)-BINAP. Similarly, Ph

3

P is an essential reaction compo-

nent only when coupling aryl bromides and chlorides. Couplings
between aryl iodides and vinyl zirconocenes are actually retarded
by Ph

3

P, resulting in low conversions.

Reductions of Aryl Halides.

19

Aryl chlorides can effec-

tively be reduced to the corresponding arenes using heterogeneous
Ni/C catalysis. Treatment of an aryl chloride with 1.1 equiv of
potassium dimethylamide-borane complex (generated prior to
the reduction by mixing commercially available Me

2

NH·BH

3

and K

2

CO

3

) initiates reduction. Under the influence of 5%

Ni/C and 10% Ph

3

P in refluxing acetonitrile, the catalyst system

required only 5–10 h to affect complete reduction (eq 9). Prior
conversion of Ni

II

/C to the active Ni

0

catalyst by n-BuLi is not

necessary as a slight excess of Me

2

NH·BH

3

/K

2

CO

3

(10 mol %)

is capable of affording active Ni

0

/C. Additional hydride sources

(silanes, H

2

, etc.) were examined in the original publication.

17

Me

2

NH·BH

3

/K

2

CO

3

proves to be most useful in affecting a

complete and clean reduction, while being unreactive toward elec-
trophilic functionality present in the aryl chloride. Thus, esters, ke-
tones, nitriles, etc. are all tolerated presumably due to the limited
Lewis acidity of the potassium salt ([Me

2

N·BH

3

]

−

K

+

) formed in

situ. As with other Ni/C heterogeneous reactions, the catalyst can
be filtered away from the reaction and reused with negligible loss
of activity.

N
H

O

Ph

Cl

N
H

O

Ph

H

96%

1. K

2

CO

3

, Me

2

NH

BH

3

(9)

2. Ni/C, Ph

3

P, CH

3

CN, ∆, 7 h

·

Coupling of Vinylalanes with Benzylic Chlorides.

20

Effi-

cient, room temperature coupling of various benzylic chlorides
with vinylalanes can be affected using 5% Ni/C as catalyst. Vinyl-
alanes can be easily derived from terminal alkynes using standard
Negishi carboalumination conditions. The versatility and prac-
ticality of this reaction, which affords stereodefined allylic aro-
matics, is exemplified by its use en route to naturally occurring
coenzyme Q

10

(eq 10).

MeO

MeO

O

H

O

MeO

MeO

OTs

H

10

coenzyme Q

10

10

(10)

The Ni

II

catalyst is best used after in situ reduction by n-

BuLi to form the active Ni

0

species. Reactions go to completion

in reasonable times without resorting to unusually high concen-
trations (ca. 0.25–0.30 M). Both electron-rich and electron-poor
substrates react with all-hydrocarbon derived or ω-functionalized
vinylalanes at roughly comparable rates. Isolated yields tend to
be good (78–94%). Preliminary investigations suggest that this
reaction is amenable to microwave assistance, leading to the same
aryl tosylate in 80% yield in only 20 min at ca. 200

◦

C (eq 11).

7

MeO

MeO

OTs

Cl

Me

2

Al

H

MeO

MeO

OTs

H

9

10

Ni/C, Ph

3

P

+

Ni/C, Ph

3

P, THF

(11)

µW, 200

°C, 20 min

80%

THF, rt, 14 h
85%

Avoid Skin Contact with All Reagents

4

NICKEL-IN-CHARCOAL

Related

Reagents.

Palladium-on-charcoal;

Nickel-on-

graphite.

6

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2.

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, 68, 1177.

3.

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Synthesis 2005

, 2989.

4.

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2139.

5.

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6.

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78

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7.

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8.

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9.

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11.

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12.

Cramer, R.; Coulson, D. R., J. Org. Chem. 1975, 40, 2267.

13.

Lipshutz, B. H.; Tomioka, T.; Blomgren, P. A.; Sclafani, J. A., Inorg.
Chim. Acta. 1999

, 296, 164.

14.

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16.

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17.

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18.

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19.

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20.

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John B. Unger & Bruce H. Lipshutz

University of California, Santa Barbara, CA, USA

A list of General Abbreviations appears on the front Endpapers