Dichlorobis(triphenylphosphine)nickel-catalyzed cross-coupling of aryl chlorides with intramolecularly stabilized group 13 metal alkylating reagents

Article abstract of DOI:10.1016/S0040-4039(00)01295-8

The intramolecularly stabilized alkyl and aryl aluminum complexes 1, 4 and 11, as well as the indium compounds 6, 9 and 10 cross-couple with a variety of chloroarenes at 8°C in the presence of NiCl₂(PPh₃)₂ to give selectively the respective alkylated arenes in high yields. Addition of organic or inorganic bases lowers the reaction temperature to 50°C. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01295-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7555–7558
Dichlorobis(triphenylphosphine)nickel-catalyzed
cross-coupling of aryl chlorides with intramolecularly
stabilized group 13 metal alkylating reagents
Dmitri Gelman,a Herbert Schumannb and Jochanan Bluma,*
aDepartment of Organic Chemistry, Hebrew University, Jerusalem 91904, Israel
bInstitut fu¨r Anorganische und Analytische Chemie, Technische Universita¨t Berlin, D-10623 Berlin, Germany
Received 16 May 2000; accepted 28 July 2000
Abstract
The intramolecularly stabilized alkyl and aryl aluminum complexes 1, 4 and 11, as well as the indium
compounds 6, 9 and 10 cross-couple with a variety of chloroarenes at 80°C in the presence of
NiCl2(PPh3)2 to give selectively the respective alkylated arenes in high yields. Addition of organic or
inorganic bases lowers the reaction temperature to 50°C. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: nickel catalyst; cross-coupling; aryl chlorides; aluminum; indium.
Although palladium-catalyzed cross-coupling of aryl iodides, bromides and pseudohalides
with organometallics in the Stille,1 Suzuki,2 Negishi3 and related processes are extremely useful
for CꢀC bond formation in academic research,4 their utilization in industrial plants is still
limited owing to the high cost of the substrates. It is thus understandable that extensive research
has lately been conducted to modify the palladium catalysts in a way that they may activate
inexpensive aryl chlorides in the above named coupling processes.5 In the course of our studies
on the cross-alkylation of aryl halides with intramolecularly stabilized dimethylaluminum
reagents,6 we found that some chloroarenes do undergo the coupling reaction when the
electron-rich [1,3-bis(diisopropylphosphino)propane]palladium is used as catalyst.7 This complex
has, however, the disadvantages of being air sensitive and expensive, and it fails to affect
unsubstituted aryl bromides.
In this communication we report the use of NiCl2(PPh3)2 (that has previously been used in
coupling reactions of Grignard reagents8) as an efficient catalyst for the cross-alkylation of
several monomeric and dimeric dialkylaluminum and indium complexes with a variety of aryl
chlorides. This catalyst is also capable of the activation of bromoarenes.
* Corresponding author. Tel: +972-2-6585329; fax: +972-2-6513832; e-mail: jblum@chem.ch.huji.ac.il
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01295-8

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When, for example, a solution of 104 mg (0.64 mmol) of 1-chloronaphthalene, 186 mg (0.64
mmol) of 1,6a and 21 mg (0.032 mmol) of NiCl2(PPh3)2 in 4.5 ml of benzene was heated at 78°C
under N2 for 3 h, followed by quenching with 4 ml of 5% aq HCl, the resulting mixture
1
consisted (according to GC and H NMR analyses) of 95% of 1-methylnaphthalene and 3% of
the unsubstituted hydrocarbon. Under similar conditions 1-bromonaphthalene gave quantitative
yields of 1-methylnaphthalene after 2 h. A series of similar cross-coupling experiments con-
ducted with several representative chloroarenes and alkylating agents 1–116a,9–12 are summarized
in Table 1.
While in the palladium-catalyzed cross-methylation of aryl bromides6 and chlorides7 both
aluminum-bound methyl groups can take part in the process, only one of the alkyl functions is
applicable in the NiCl2(PPh3)2-catalyzed cross-coupling. When, for example, 1-chloronaph-
thalene was reacted with just half an equivalent of 1 (i.e. 0.25 mol of the reagent per each mol
of substrate) the yield after 48 h was only 42% (entry 8), and did not exceed 50% even after
extension of the reaction time. Table 1 indicates that both unsubstituted and substituted
chlorobenzenes undergo cross-methylation with 1. Substrates with electron-withdrawing sub-
stituents react faster than those with electron-donating groups (cf. entries 4–6 vs. entries 2,3).
Likewise, 2-chloronaphthalene reacts faster than the 1-isomer in which the chlorine atom is
sterically hindered. The cross-coupling with 1 tolerates the presence of cyano as well as keto-
and ester-carbonyl moieties (entries 4–6), but in chlorobenzaldehyde both vulnerable groups are
affected by the reagent (entry 7). The indium analog of 1, complex 6, reacts much slower than
the aluminum reagent (see entries 1, 9, 14 and 15), and the gallium complex 5 hardly reacts at
all (1-C10H7Cl forms only 1% of 1-C10H7Me after 24 h). The monomeric methylating reagents
7–11 react usually faster than the dimeric analogs. The aluminum and gallium complexes react,
however, in a non-selective fashion. Thus, compound 7 yields during the reaction with
1-C10H7Cl mainly naphthalene and only 27% of the methylated product (entry 16). Likewise, the
monomeric gallium complex gives both methylated and unsubstituted naphthalene (entry 17).
The indium methylating reagent 9 (which reacts much faster than 6), yields solely 1-methylnaph-
thalene (entry 18). Also, complex 11, which is more bulky than 7, forms the expected product
in a highly selective manner (entry 20). The NiCl2(PPh3)2-catalyzed reactions of chloroarenes
with analogs of 1 in which the Me moiety has been replaced by Et, i-Bu and Ph have also been
studied. While the phenylated complex 4 reacts with 2-chloronaphthalene to give solely
2-phenylnapthalene (entry 13), reagents 2 and 3 which may lose ethylene and i-butene,
respectively, to give aluminum hydrides,13 form naphthalene as the major product (entries 11,
12). Rather unexpectedly, reagent 7 also gives mainly naphthalene, but the indium complexes 9
and 10 cross-couple with 1-chloronaphthalene in a highly selective manner to give exclusively
1-methyl- and 1-ethylnaphthalene, respectively (entries 18, 19).

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Table 1
a
Cross-coupling of some representative aryl chlorides with complexes 1–11 in the presence of NiCl2(PPh3)2
Entry
Substrate
Alkylating
reagent
Substrate:metal
atomb
Reaction
time (h)
Products (yield, %)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
C6H5Clc
1
1
1
1
1
1
1
1
1
1
2
3
4
6
6
7
8
1:1
1:1
1:2
1:2
1:2
1:2
1:2
2:1
1:1
1:2
1:2
1:2
1:2
1:1
1:2
1:2
1:2
1:2
1:2
1:2
5
20
20
6
4
4
3.5
48
8
C6H5Me (91)
4-MeC6H4Clc
4-MeOC6H4Cl
4-ClC6H4CN
4-ClC6H4COMe
4-ClC6H4CO2Et
4-ClC6H4CHO
1-C10H7Cl
1,4-C6H4Me2 (24)d
4-MeOC6H4Me (46)d
4-MeC6H4CN (96)
4-MeC6H4COMe (91)
4-MeC6H4CO2Et (81)
4-MeC6H4CH(OH)Me (91)e
1-C10H7Me (42)d
1-C10H7Cl
2-C10H7Cl
2-C10H7Cl
2-C10H7Cl
1-C10H7Me (92)f
3
2-C10H7Me (95)f
24
24
8
20
24
3
5
5
5
5
2-C10H7Me (36), C10H8 (60)
2-C10H7Me (22), C10H8 (76)
2-C10H7Ph (93)
2-C10H7Cl
C6H5Clc
C6H5Me (66)d
1-C10H7Cl
1-C10H7Cl
1-C10H7Cl
1-C10H7Cl
1-C10H7Cl
1-C10H7Cl
1-C10H7Me (7)d
1-C10H7Me (27), C10H8 (70)
1-C10H7Me (43), C10H8 (55)
1-C10H7Me 91)
9
10
11
1-C10H7Me (95)
1-C10H7Me (94)f
a Reaction conditions: 0.64 mmol chloro compound, the appropriate amount of the alkylating agent and 0.032
mmol of NiCl2(PPh3)2 in 4.5 ml of benzene; 80°C; quenching with excess 5% aq HCl.
b Calculated for each metal atom as if complexes 1–6 reacted as monomeric species.
c In C6D6.
d The missing percentages reflect the unreacted starting chloroarene.
e Contaminated with 7% of 4-MeC6H4CH2OH.
f Contaminated with 1–3% of naphthalene.
Finally, it is notable that unlike the Suzuki reaction,2 the cross-coupling with stabilized group
13 metal reagents does not require the presence of a base. However, the addition of some bases
enhances the reaction rate and lowers the temperature. While, for example, 1-chloronaph-
thalene, 1, and NiCl2(PPh3)2 (substrate:reagent:catalyst=1:1:0.02) form upon heating at 50°C
for 24 h, 64% of 1-methylnaphthalene and 2% of the unsubstituted hydrocarbon, the addition
of 0.06 equivalents of NBu3, Cs2CO3 or K3PO4 leads to the formation of 96, 92 and 91% of the
methylated product, respectively, under the same experimental conditions.
Acknowledgements
We thank the Israel Science Foundation and the Exchange Program between the Technische
Universita¨t, Berlin and the Hebrew University of Jerusalem for financial support.

7558
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1
MHz H NMR (C6D6): l 0.05 (q, 8, J=9 Hz), 1.39 (t, 12, J=9 Hz), 1.88 (s, 12), 1.98 (t, 4, J=6 Hz), 3.49 (t,
4, J=6 Hz); 100 Mz 13C NMR (C6D6): l 1.17, 11.82, 45.30, 57.33, 59.82. 3: Yield: 43%; mp 114°C; 300 MHz
1H NMR (C6D6): l 0.03 (d, 8, J=9 Hz), 1.25 (d, 24, J=6 Hz), 1.95–1.98 (m, 4), 1.99 (t, 4, J=6 Hz), 3.55 (t, 4,
J=6 Hz); 100 Mz 13C NMR (C6D6): l 23.70, 27.84, 29.90, 46.21, 57.66, 60.20. 4: Yield: 68%; mp ꢀ200°C; 300
1
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100 Mz 13C NMR (C6D6): l 45.77, 55.84, 58.98, 127.21, 127.59, 128.08, 138.47. Further analytical data of
compounds 2–4 will be published elsewhere.
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