Bidentate P, N-P ligand for nickel-catalyzed cross-coupling of aryl or benzyl chlorides with ArMgX

Article abstract of DOI:10.1021/jo1016458

A cross-coupling reaction of a variety of aryl, heteroaryl, and benzyl chlorides with ArMgX is catalyzed by 2 mol % of a nickel-phosphine complex prepared in situ from an equimolar amount of Ni(CH₃CN) ₂Cl₂ and ligand (L2) to yield products in excellent yield in THF at room temperature. This new bidentate ligand (L2) is stable in air and forms a stable complex upon reaction with Ni(CH₃CN) ₂Cl₂. Structures of the ligand and the complex were confirmed by single-crystal X-ray diffraction.

Full text of DOI:10.1021/jo1016458

pubs.acs.org/joc
synthetic step. Kumada and Corriu independently reported
Bidentate P, N-P Ligand for Nickel-Catalyzed
Cross-Coupling of Aryl or Benzyl Chlorides
with ArMgX
in 1972 the first cross-coupling reaction of aryl halides and
Grignard reagents.6 The Kumada-Corriu reaction has re-
ceived greater attention after Knochel et al. introduced well-
designed synthetic routes to organomagnesium and organo-
zinc compounds featuring functionalities like ester, nitro,
aldehyde, nitrile, etc.7
Raju Ghosh and Amitabha Sarkar*
Department of Organic Chemistry, Indian Association for the
Cultivation of Science, Jadavpur, Kolkata 700032, India
Aryl bromides and iodides have been regularly used in this
reaction.8 Chlorides, on the other hand, are much less used
despite their lower cost and greater availability.9 The work
of Buchwald, Hartwig, Fu, and others demonstrated that
electron-rich alkyl- or arylalkylphosphines play a crucial
role in C-Cl bond activation.10 More recently, new catalytic
systems have been developed to make the aryl chlorides
participate in the reaction.11,12 We have recently reported
the use of air-stable aminophosphine ligand L1 (Figure 1) for
ocas@iacs.res.in
Received August 20, 2010
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A cross-coupling reaction of a variety of aryl, heteroaryl,
and benzyl chlorides with ArMgX is catalyzed by 2 mol %
of a nickel-phosphine complex prepared in situ from
an equimolar amount of Ni(CH3CN)2Cl2 and ligand (L2)
to yield products in excellent yield in THF at room
temperature. This new bidentate ligand (L2) is stable
in air and forms a stable complex upon reaction with
Ni(CH3CN)2Cl2. Structures of the ligand and the com-
plex were confirmed by single-crystal X-ray diffraction.
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DOI: 10.1021/jo1016458
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Published on Web 11/08/2010
J. Org. Chem. 2010, 75, 8283–8286 8283
2010 American Chemical Society

Ghosh and Sarkar
SCHEME 2. Synthesis of Nickel-Phosphine Complex
JOCNote
FIGURE 1. Ligand structure.
the palladium-catalyzed Suzuki-Miyaura cross-coupling
reaction of chloroarenes.13
In continuation of this study, we report the use of an
analogous air-stable, chelating aminophosphine ligand L2
(Scheme 1) for Kumada-Corriu cross-coupling reaction of
chloroarenes catalyzed by nickel.
air-stable complex (1d) was grown from DCM/CH3CN (4:1)
for X-ray diffraction analysis. The nickel complex (1d) was
found to have a distorted square-planar geometry.
Kumada-Corriu coupling reaction was carried out with
chloroanisole (2a) and phenylmagnesium bromide (1e) in
THF. The catalytic species is generated in situ when a
nickel(II) salt was added to the ligand (L2). It was observed
that the reaction proceeded well at ambient temperature for
10 h. The bis-acetonitrile complex of NiCl2 was clearly the
best catalyst precursor (see Table 1). As seen from entry 1,
Table 1, L2 gives a better yield of product (92%) compared to
that obtained with L1 (73%).
SCHEME 1. Synthesis of Ligand
TABLE 1. Optimization of the Cross-Coupling Reaction of Aryl
Chloride with Grignard reagenta
The indole scaffold of the ligand (L2) was constructed by a
two-step process. Condensation of commercially available
1-bromo-2-nitrobenzene (1b) and propenylmagnesium bro-
mide solution (1a) at -45 °C gave 7-bromo-3-methyl-1H-
indole (1c) as reported.14 Treatment of this compound with
2.2 equiv of nBuLi at -78 °C resulted in the formation of a
dianion which was quenched by 2.2 equiv of PPh2Cl to afford
the desired bidentate phosphine ligand (L2) in 40% yield.
The pure product was obtained after column chromatog-
raphy followed by crystallization from petroleum ether as
colorless, transparent crystals adequate for crystallographic
structure determination (see the Supporting Information).
This newly synthesized ligand (L2) is stable in air both as a
solid and in solution for more than a week.
entry
Ni precursor (mol %)
L (mol %)
yield (%)
1
2
3
4
5
6
7
8
9
Ni(CH3CN)2Cl2 (2)
Ni(CH3CN)2Cl2 (2)
Ni(CH3CN)2Cl2 (2)
Ni(CH3CN)2Cl2 (2)
Ni(CH3CN)2Cl2 (1)
Ni(CH3CN)2Cl2 (1)
NiCl2 (2)
2
2
1.5
1.75
1
2
2
2
2
92 (73)b
75c
77
84
71
62
76
72
66
Ni(acac)2 (2)
Ni(DME)2Br2 (2)
a4-Chloroanisole (1.0 mmol), Ni precursor, and L2 in 1 mL of THF
under argon atmosphere was treated with 1 M PhMgBr (2.0 mmol) and
then stirred at rt. bL1 was used. cReaction at -20 °C.
The Ni-L2 complex (1d) was synthesized by treatment of
Ni(CH3CN)2Cl2 with the phosphine ligand (L2) in a 1:1 ratio
in dichloromethane (Scheme 2).13 A single crystal of the
The results show that optimal yield of product was ob-
tained with 2 mol % of Ni(CH3CN)2Cl2 (entry 1) with a
ligand-metal ratio of 1:1 under the conditions employed.
The yield of product decreased if the Ni/L ratio was altered
(11) (a) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889.
€
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(b) Bohm, V. P. W.; Weskamp, T.; Gstottmayr, C. W. K.; Herrmann, W. A.
Angew. Chem., Int. Ed. 2000, 39, 1602. (c) Li, G. Y.; Marshall, W. J.
Organometallics 2002, 21, 590. (d) Park, S. Y.; Kang, M.; Yie, J. E.; Kim,
J. M.; Lee, I. Tetrahedron Lett. 2005, 46, 2849. (e) Ackermann, L.; Born, R.;
Spatz, J. H.; Meyer, D. Angew. Chem., Int. Ed. 2005, 44, 7216. (f) Wang, Z.;
Wang, L. Chem. Commun. 2007, 2423. (g) Inamoto, K.; Kuroda, J.;
Sakamoto, T.; Hiroya, K. Synthesis 2007, 2853. (h) Zhou, Y.; Xi, Z.; Chen,
W.; Wang, D. Organometallics 2008, 27, 5911. (i) Gu, S.; Chen, W. Organo-
metallics 2009, 28, 909. (g) Chen, X.; Wang, L.; Liu, J. Synthesis 2009, 2408.
(12) (a) Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1513. (b) Frisch, A. C.;
Rataboul, F.; Zapf, A.; Beller, M. J. Organomet. Chem. 2003, 687, 403.
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17978. (d) Ackermann, L.; Gschrei, C. J.; Althammer, A.; Riederer, M.
ꢁ
(entries 3, 4, and 6 vis-a-vis entry 1).
As depicted in Table 2, a variety of aryl and heteroaryl
chlorides were coupled with an aryl Grignard reagent
in excellent yield. It was observed that use of 2 equiv of
Grignard reagent gave the most consistent and highest
yield.15 The products were identified on the basis of their
1H and 13C NMR spectra. As anticipated, in case of aryl
iodide the reaction was complete within 30 min (entry 12),
while the corresponding aryl bromide required 2 h for
completion (entry 13).
Chem. Commun. 2006, 1419. (e) Organ, M. G.; Abdel-Hadi, M.; Avola, S.;
;
ꢀ
Hadei, N.; Nasielski, J.; OBrien, C. J.; Valente, C. Chem. Eur. J. 2007, 13,
150. (f) Wolf, C.; Xu, H. J. Org. Chem. 2008, 73, 162. (g) Xi, Z.; Liu, B.; Chen,
W. J. Org. Chem. 2008, 73, 3954.
(15) Part of the reagent is used up in the reduction of Ni(II) to Ni(0), and
operation of Schlenck equilibrium to further reduce active ArMgX also
cannot be ruled out; for previous examples of using 2 equiv of reagent, see refs
8h and 16b.
(13) Ghosh, R.; Adarsh, N. N.; Sarkar, A. J. Org. Chem. 2010, 75, 5320.
(14) Dobbs, A. J. Org. Chem. 2001, 66, 638.
8284 J. Org. Chem. Vol. 75, No. 23, 2010

Ghosh and Sarkar
JOCNote
TABLE 3. Kumada-Corriu Cross-Coupling Reaction of Benzyl
TABLE 2. Kumada-Corriu Cross-Coupling Reaction of Aryl and
Chloridesa
Heteroaryl Chloridesa
aChloroarene (1 mmol), Ni(CH3CN)2Cl2 (2 mol %), and phosphine
ligand (2 mol %) in 1 mL of THF under argon atmosphere was treated
with Grignard reagent (2 mmol) and then stirred at rt. bReaction without
Ni catalyst.
aAryl chloride (1 mmol), Ni(CH3CN)2Cl2 (2 mol %), and phosphine
ligand (2 mol %) in 1 mL of THF under argon atmosphere was treated
with Grignard reagent (2 mmol) and then stirred at rt.
cross-coupling reactions of aryl, heteroaryl, and benzyl
chlorides.
Although Kumada-Corriu coupling reaction of benzyl
chlorides has been rarely reported,16 benzyl chlorides
smoothly reacted under the present reaction condition
(Table 3).17
In summary, we have described an air-stable, bidentate
ligand featuring an indole scaffold and a N-P donor that can
be used very effectively in nickel-catalyzed Kumada-Corriu
Experimental Section
Preparation of Ligand L2 from 7-Bromo-3-methyl-1H-indole
(1c). To a stirred solution of 7-bromo-3-methyl-1H-indole (1c)
(2.10 g, 10 mmol) in THF (50 mL), under argon atmosphere, was
added nBuLi (13.75 mL, 22 mmol, 1.60 M in hexane) dropwise at
-78 °C. The mixture was slowly warmed to room temperature
and then stirred for an additional 2 h at rt. After the mixture was
cooled to -78 °C, chlorodiphenylphosphine (4.06 mL, 22 mmol)
in THF (10 mL) was added dropwise. The mixture was then
warmed to room temperature and stirred for an additional 2 h.
It was then quenched with saturated NH4Cl solution at 0 °C
and extracted with diethyl ether (2 Â 100 mL). The combined
organic layer was washed subsequently with water and brine and
dried over anhydrous Na2SO4. Evaporation of solvent under
(16) (a) Tsai, F.; Lin, B.; Chen, M.; Mou, C.; Liu, S. Tetrahedron 2007, 63,
4304. (b) Chowdhury, R. R.; Crane, A. K.; Fowler, C.; Kwong, P.; Kozak,
C. M. Chem. Commun. 2008, 94.
(17) We observed that with allyl chloride the coupling product can be
obtained in high yield without any catalyst. Hence, such examples were not
included in this revision. We thank a reviewer for bringing this issue to our
attention.
J. Org. Chem. Vol. 75, No. 23, 2010 8285

Ghosh and Sarkar
JOCNote
reduced pressure gave the crude product. Purification by flash
column chromatography (silica gel, 2.2% ethyl acetate/pet
ether) afforded ligand L2 as a white solid (2.0 g, 40%): 1H
NMR (300 MHz, CDCl3, ppm) δ 7.56 (d, J = 7.7 Hz, 1H),
7.38-7.27 (m, 17H), 7.08 (t, J = 7.3 Hz, 4H), 6.73 (t, J = 6.5 Hz,
1H), 6.67 (s, 1H), 2.24 (s, 3H); 13C NMR (75 MHz, CDCl3, ppm)
δ 138.2, 138.1, 138.0, 138.0, 137.8, 137.7, 134.7, 134.7, 134.5,
134.4, 132.3, 132.0, 131.2, 129.5, 129.3, 128.6, 128.5, 128.5,
128.5. 128.2, 120.6, 119.9, 116.0, 10.0; 31P NMR (202.44 MHz,
CDCl3, ppm) δ 35.08 (d, J = 159.9 Hz), -16.26 (d, J =161.9
Hz). Anal. Calcd for C33H27NP2: C, 79.35; H, 5.45; N, 2.80.
Found: C, 79.33; H, 5.42; N, 2.79.
Typical Procedure for the Cross-Coupling Reaction. To a
stirred solution of ligand (10.0 mg, 0.02 mmol), Ni(CH3CN)2Cl2
(4.2 mg, 0.02 mmol), and chloroarene (1.0 mmol) in 1 mL of dry
THF under argon atmosphere was added aryl Grignard reagent
1(M) in THF (2.0 mmol) at ambient temperature. The reaction
mixture was then stirred for a further 3-10 h (depending on
substrate) at rt. It was then quenched with saturated NH4Cl
solution at 0 °C and extracted with diethyl ether (2 Â 10 mL).
The combined organic layer was washed subsequently with
water and brine and dried over anhydrous Na2SO4. The solvent
was removed under reduced pressure, and the residue was puri-
fied by flash chromatography on silica gel (230-400 mesh) with
either a mixture of petroleum ether and acetone (2-8%) or
petroleum ether alone as eluent.
Acknowledgment. We thank the DST-funded National
Single Crystal Diffractometer Facility of IACS and Prof.
Alexander J. Blake, School of Chemistry, Nottingham
University, UK, for crystal structure solution. R.G. is thankful
to CSIR, India, for his fellowship.
Supporting Information Available: Detailed experimental
procedures and characterization data for all compounds and
X-ray data for 1d and L2 (CIF). This material is available free of
charge via the Internet at http://pubs.acs.org.
8286 J. Org. Chem. Vol. 75, No. 23, 2010