Nickel-catalyzed vinylation of aryl chlorides and bromides with vinyl ZnBr · MgBrCl

Article abstract of DOI:10.1021/jo900290t

The Ni-catalyzed cross-coupling of aryl halides and vinylzinc bromide for the synthesis of styrene derivatives was investigated. Of the catalysts surveyed, the combination of Ni(acac)₂ and Xantphos was found to be the most effective for this cr

Full text of DOI:10.1021/jo900290t

Nickel-Catalyzed Vinylation of Aryl Chlorides
SCHEME 1. Transition Metal-Catalyzed Synthesis of
Styrenes
and Bromides with Vinyl ZnBr ·MgBrCl
Tetsuya Yamamoto and Tetsu Yamakawa*
Sagami Chemical Research Center, 2743-1 Hayakawa,
Ayase, Kanagawa 252-1193, Japan
t_yamakawa@sagami.or.jp
ReceiVed February 9, 2009
because various metallic reagents that are compatible with a
wide range of substituents can be used in this reaction.
Aryl chlorides are arguably the most useful for cross-coupling
6
7
reactions because of their cost and availability. Vinylboron,
8
9
10
vinylsilicone, vinylzinc, and vinyltin reagents have been used
in the Pd-catalyzed vinylation of aryl chlorides. In contrast, only
vinyltin reagents are known to be used in the Ni-catalyzed
The Ni-catalyzed cross-coupling of aryl halides and vinylzinc
bromide for the synthesis of styrene derivatives was inves-
tigated. Of the catalysts surveyed, the combination of
1
1
vinylation.
In this study, we investigated Ni-catalyzed cross-coupling of
aryl halides and vinylzinc bromide. We found that the combina-
2
Ni(acac) and Xantphos was found to be the most effective
for this cross-coupling. This catalyst could be used in
reactions with various aryl bromides and chlorides, including
electron-rich aryl chlorides such as chloroanisoles.
tion of Ni(acac) and Xantphos was the most effective catalyst
and that it could be successfully used in the synthesis of various
styrene derivatives from aryl bromides and chlorides.
Table 1 shows the results of the vinylation of ethyl 4-bro-
mobenzoate (1a). Of the Ni complexes and ligands tested, the
2
combination of Ni(acac)
rarely used in the Ni-catalyzed cross-coupling reaction,
resulted in satisfactory yields even at short reaction times (entries
2 2
or Ni(cod) with Xantphos, which is
Styrene derivatives can be transmuted into various functional
1
2
1
polymers; they are also often used as key building blocks in
2
fine chemical synthesis and total synthesis. As pointed out by
1
1 and 12).
Denmark in a recent review, Pd- and Ni-catalyzed cross-
coupling reactions appear to be a versatile means for the
We found Ni-catalyzed Negishi coupling for vinylation for
3
synthesis of styrene derivatives. These reactions are classified
the first time; therefore, we examined the use of the Ni-Xantphos
catalyst in the vinylation of various aryl halides. The results
are shown in Table 2. This catalyst also enabled the production
of 1-vinylnaphthalene (2b) and 4-vinylbiphenyl (2c) from 1b
and 1c in satisfactory yields (entries 1 and 2). It is worth
mentioning that 2a was also obtained from ethyl 4-chloroben-
zoate (3a) in a moderate yield by using this catalyst (entry 3).
We believe that this is the first example of vinylation of aryl
chlorides through the cross-coupling reaction using vinylzinc
reagents. In contrast, the yield of 1-ethenyl-4-methoxybenzene
(2d) obtained from 4-bromoanisole (1d) was rather low (entries
into two types: one type is the coupling of vinyl electrophiles
and aryl metallic reagents, and the other type is the coupling of
aryl electrophiles and vinyl metallic reagents (Scheme 1). The
only example of the former type of reaction involving vinyl
4
halides is the Ni-catalyzed coupling of aryl magnesium reagents
5
and vinyl chloride. This reaction is currently employed in the
industrial manufacture of some styrene derivatives; however,
substrates that can be used in this reaction are limited by the
tolerance of a substituent for magnesium. In contrast, the latter
type of reaction is applicable to a wide range of aryl compounds,
4
and 5). This result indicates that the Ni-Xantphos catalyst
(
1) (a) Scheirs, J.; Priddy, D. B. Eds. Modern Styrenic Polymers; John Wiley:
was not suitable for the vinylation of a substrate that possesses
an electron-donating substituent, even in the case when the
substrate was an aryl bromide.
Chichester, UK, 2003. (b) Hirao, A.; Loykulnant, S.; Ishizone, T. Prog. Polym.
Sci. 2002, 27, 1399–1471. (c) Schellenberg, J.; Tomotsu, N. Prog. Polym. Sci.
2
002, 27, 1925–1982. (d) Nair, C. R. Prog. Polym. Sci. 2004, 29, 401–498. (e)
Wallraff, G. M.; Hinsberg, W. D. Chem. ReV. 1999, 99, 1801–1821.
2) (a) Agbossou, F.; Carpentier, J.-F.; Mortreux, A. Chem. ReV. 1995, 95,
485–2506. (b) F u¨ rstner, A.; Thiel, O. R.; Kindler, N.; Bartkowska, B. J. Org.
(
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(6) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176–4211.
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(8) Alacid, E.; N a´ jera, C. J. Org. Chem. 2008, 73, 2315–2322.
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(10) (a) Littke, A. F.; Schwartz, L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
6343–6348. (b) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001, 3, 119–122.
(11) (a) Shirakawa, E.; Yamasaki, K.; Hiyama, T. Synthesis 1998, 1544–
1549. (b) Shirakawa, E.; Yamasaki, K.; Hiyama, T. J. Chem. Soc., Perkin Trans.
1 1997, 2449–2450.
Chem. 2000, 65, 7990–7995. (c) Li, M.; O’Doherty, G. A. Org. Lett. 2006, 8,
087–6090. (d) Shin, I.; Choi, E.-S.; Cho, C.-G. Angew. Chem., Int. Ed. 2007,
6, 2303–2305.
(
(
vinyl electrophile, see: Gøgsig, T. M.; Søbjerg, L. S.; Lindhardt, A. T.; Jensen,
K. L.; Skrydstrup, T. J. Org. Chem. 2008, 73, 3404–3410.
(
6
4
3) Denmark, S.; Butler, C. R. Chem. Commun. 2009, 20, 33.
4) Reentry vinylation of various arylboronic acids with vinyl tosylate as a
5) Banno, T.; Hayakawa, Y.; Umeno, M. J. Organomet. Chem. 2002, 653,
2
88–291.
(12) Roques, N.; Saint-Jalmes, L. Tetrahedron Lett. 2006, 47, 3375–3378.
1
0.1021/jo900290t CCC: $40.75  2009 American Chemical Society
J. Org. Chem. 2009, 74, 3603–3605 3603
Published on Web 04/08/2009

TABLE 1. Survey of Catalysts
TABLE 2. Ni(acac)2-Xantphos-Catalyzed Coupling of Vinylzinc
Bromide and Various Aryl Halides
a
entry
catalyst
(PPh
(dppm)
(dppe)
(dmpe)
(dppp)
(dppb)
(dppf)
yield (%)
1
2
3
4
5
6
7
8
9
NiCl
NiCl
NiCl
NiCl
NiCl
NiCl
NiCl
2
2
2
2
2
2
2
3
)
2
1
1
35
10
10
4
5
0
1
a
aryl halide/
product
addition time
(h)/reaction time (h)
conversion (%) /
b
entry
yield (%)
c
1
1b/2b
1c/2c
3a/2a
1d/2d
1d/2d
1d/2d
1d/2d
1d/2d
1d/2d
1d/2d
0/4
0/6
0/12
0/18
0/18
1/1
2/1
4/1
2/1
0/6
97/92
97/73
97/62
29/(6)
30/(19)
70/(62)
82/(74)
92/(67)
Ni(acac)
Ni(acac)
Ni(acac)
Ni(acac)
2
2
2
2
+ phenanthroline
+ (S)-iPr-pybox
+ Dpephos
2
3
4
10
11
12
43
c
b
+ Xantphos
86
74
5
6
7
8
b
Ni(cod)
2
+ Xantphos
a
Yield based on GC analysis relative to an internal standard.
b
Reaction time was 6 h.
d
9
92/81(89)
25/(3)
d
1
0
To overcome this limitation, we changed the manner of
a
b
Determined by GC used an internal standard method. Isolated
addition of the THF solution of vinylzinc bromide, i.e., the
solution was charged along with the catalyst and the substrate
during the initial surveys: the results of all entries in Table 1
and entries 1-5 in Table 2. It is known that the dropwise
addition of a metallic reagent (slow addition) frequently
yield. The yields in parentheses are GC analysis relative to an internal
standard. Reaction temperature was 50 °C. 20 mol % of MesMgBr
was added.
c
d
1
3
aryl chlorides, 4-chloro- (3d) and 3-chloroanisole (3e), pro-
ceeded smoothly (entries 5 and 7). The lower yields obtained
in the case of 2-bromoanisole (1f) and 2-chloroanisole (3f) could
be due to steric hindrance (entries 8 and 9).
improves yield in cross-coupling reactions. Therefore, we
added the THF solution of vinylzinc bromide in a dropwise
manner to the 1d reaction mixture at 70 °C for 1-2 h (addition
time) and kept the temperature of the mixture for 1 h (reaction
time). Consequently, the 2d yield showed remarkable improve-
ment despite the total reaction time being only 2-3 h (entries
In conclusion, we report that the combination of Ni(acac)
2
and Xantphos is an efficient catalyst for the vinylation of various
aryl halides with vinylzinc bromide. Slow addition of vinylzinc
bromide is the key to obtaining a high yield. This reaction
appears to be a versatile means for the synthesis of styrene
derivatives with various substituents, not only from aryl
bromides but also from aryl chlorides.
6
and 7). Carrying out this reaction with an addition time of
longer than 2 h led to a lower yield (entry 8). Slow addition
was also efficient in the presence of MesMgBr, which is
prereductant of Ni(II), providing the highest yield of 2d (entry
9
). In contrast, both the conversion and yield were drastically
reduced when slow addition was not employed at the same
conditions used in entry 9 (entry 10). The detailed effect of
slow addition is presently unknown and is under investigation.
Since slow addition in the presence of MesMgBr produced
the highest yield in the reaction with 1d, it was used for the
vinylation of various aryl bromides and chlorides. Table 3 shows
the best yields among several reactions carried out at different
addition times. Satisfactory yields were obtained in the case of
all substrates including halopyridines 1j and 3j (entries 16 and
Experimental Section
General Procedure for Ni-Catalyzed Vinylation of Aryl
Halides (all entries in Table 1 and entries 1-5 in Table 2). In
a 10 mL test tube sealed with a rubber septum, Ni catalyst (0.075
mmol) was dissolved in dry THF (2.0 mL) by stirring with
a magnetic stirring bar under an Ar atmosphere. An aryl halide
(
1.5 mmol) and 1.8 mL of a 1.0 mol/L THF solution of vinylzinc
bromide (1.8 mmol) were then added to the solution at room
1
7). It is worth mentioning that the vinylation of electron-rich
temperature. The reaction mixture was stirred at 50 or 70 °C for
4
-18 h. After the reaction mixture was cooled to room temperature,
(
13) (a) Manolikakes, G.; Hernandez, C. M.; Schade, M. A.; Metzger, A.;
a saturated aqueous solution of NH Cl (3.0 mL) was added. An
4
Knochel, P. J. Org. Chem. 2008, 73, 8422–8436. (b) Manolikakes, G.; Schade,
M. A.; Hernandez, C. M.; Mayr, H.; Knochel, P. Org. Lett. 2008, 10, 2765–
768. (c) Cahiez, G.; Duplais, C.; Moyeux, A. Org. Lett. 2007, 9, 3253–3254.
d) Nakamura, M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am. Chem. Soc. 2004,
26, 3686–3687.
aliquot of the organic layer of the reaction mixture was diluted
with hexane (7.0 mL) and the solution was subjected to quantitative
analysis by GC. The desired product was extracted into hexane (2
× 7.0 mL) and then into AcOEt (7.0 mL). The organic layers were
2
(
1
3
604 J. Org. Chem. Vol. 74, No. 9, 2009

TABLE 3. Vinylation of Various Aryl Chlorides and Bromides
flash chromatography (hexane), giving 214 mg of 1-ethenylnaph-
1
thalene as a white solid (92%). R
f
0.36 (hexane); H NMR (CDCl
00 MHz) δ 8.10 (d, 1H, J ) 8.0 Hz), 7.83 (d, 1H, J ) 7.7 Hz),
.77 (d, 1H, J ) 8.1 Hz), 7.61 (d, 1H, J ) 7.0 Hz), 7.42-7.51 (m,
3
,
5
7
4
1
3
H), 5.78 (d, 1H, J ) 17.3 Hz), 5.46 (d, 1H, J ) 10.9 Hz);
C
NMR (CDCl
26.2, 125.8, 125.7, 123.9, 123.7, 117.2; m/z (MS) 154 [M] .
General Procedure for Ni-Catalyzed Vinylation of Aryl
3
, 125 MHz) δ 135.7, 134.5, 133.7, 131.2, 128.6, 128.2,
+
1
Halides (slow addition, entries 6-9 in Table 2 and all entries
in Table 3). In a 10 mL test tube sealed with a rubber septum,
Ni(acac) (0.075 mmol) and Xantphos (0.075 mmol) were dissolved
2
in dry THF (1.5 mL) with a magnetic stirring bar under an Ar
atmosphere. An aryl halide (1.5 mmol) and 0.3 mL of a 1.0 mol/L
THF solution of mesitylmagnesium bromide (0.3 mmol) were added
to the solution at room temperature and the resulting mixture was
stirred at 70 °C. The prepared THF solution of vinylzinc bromide
(
[vinylzinc bromide] ) 1.0 mol/L, 1.8 mL) was added dropwise to
the solution for 1-6 h. Then the reaction mixture was stirred at 70
C for 1 h. After the reaction mixture was cooled to room
temperature, a saturated aqueous solution of NH Cl (3.0 mL) was
°
a
b
entry aryl halide/product addition time (h) conversion (%) /yield (%)
4
added. An aliquot of the organic layer of the reaction mixture was
diluted with hexane (7.0 mL) and the solution was subjected to
quantitative analysis by GC. The desired product was extracted into
hexane (2 × 7.0 mL) and then AcOEt (7.0 mL). The organic layer
was combined and concentrated in vacuo. The obtained crude
residue was purified by passing it through a silica gel column with
a hexane/ethyl acetate (100:0 to 100:5) eluent.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1a/2a
3a/2a
1c/2c
1d/2d
3d/2d
1e/2e
3e/2e
1f/2f
2
6
2
2
5
2
5
2
6
2
4
2
4
2
3
2
4
91/79
91/70
99/84
89/81
87/81
100/78
93/70
98/71
81/62
99/89
97/79
100/77
96/68
99/86
100/76
100/76
100/71
14
1-Ethenyl-4-methoxybenzene (2d). To a solution of Ni(acac)
19.3 mg, 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol), and
-chloroanisole (214 mg, 1.5 mmol) in dry THF (1.5 mL) was added
2
3f/2f
(
4
0
1
2
3
4
5
6
7
1g/2g
3g/2g
1h/2h
3h/2h
1i/2i
3i/2i
1j/2j
a THF solution of MesMgBr ([MesMgBr] ) 1.0 mol/L, 0.3 mL)
under Ar atmosphere at room temperature. 1.8 mL of a 1.0 mol/L
THF solution of vinylzinc bromide (1.8 mmol) was added dropwise
to the solution for 5 h at 70 °C. The reaction mixture was stirred
at 70 °C for 1 h. After it was cooled to room temperature, a saturated
3j/2j
4
aqueous solution of NH Cl (3.0 mL) was added to it. An aliquot
of the organic layer of the reaction mixture was diluted with hexane
(7.0 mL) and the solution was subjected to quantitative analysis
by GC, then NH Cl (3.0 mL) was added to it. An aliquot of the
4
a
Yield based on GC analysis relative to an internal standard.
Reaction time was 6 h.
b
organic layer of the reaction mixture was diluted with hexane (7.0
mL) and the solution was subjected to quantitative analysis by GC.
The desired product was extracted into hexane (2 × 7.0 mL) and
then AcOEt (7.0 mL). The organic layer was combined and
concentrated in vacuo. The obtained crude residue was purified by
combined and concentrated in vacuo. The obtained crude residue
was purified by passing it through a silica gel column with a hexane/
ethyl acetate (100:0 to 100:1) eluent.
1
4
1
2
-Ethenylnaphthalene (2b). To a solution of Ni(acac) (19.3
mg, 0.075 mmol), Xantphos (43.4 mg, 0.075 mmol), and 1-bro-
monaphthalene (311 mg, 1.5 mmol) in dry THF (2 mL) was added
flash chromatography (hexane), giving 163 mg of 1-ethenyl-4-
1
methoxybenzene as a colorless liquid (81%). R
NMR (CDCl
J ) 8.4 Hz), 6.63 (dd, 1H, J ) 17.2 Hz, 10.9 Hz), 5.58 (d, 1H, J
f
0.16 (hexane); H
1
.8 mL of a 1.0 mol/L THF solution of vinylzinc bromide (1.8
mmol) under Ar atmosphere. The mixture was stirred for 4 h at
0 °C; after it was cooled to room temperature, a saturated aqueous
solution of NH Cl (3.0 mL) was added. An aliquot of the organic
3
, 500 MHz) δ 7.30 (d, 2H, J ) 8.4 Hz), 6.81 (d, 2H,
5
13
)
17.6 Hz), 5.09 (d, 1H, J ) 10.8 Hz), 3.72 (s, 3H); C NMR
4
(
CDCl , 125 MHz) δ 159.5, 136.4, 130.6, 127.6, 114.1, 111.6, 55.3;
3
layer of the reaction mixture was diluted with hexane (7.0 mL)
and the solution was subjected to quantitative analysis by GC. The
desired product was extracted into hexane (2 × 7.0 mL) and then
into AcOEt (7.0 mL). The organic layers were combined and
concentrated in vacuo. The obtained crude residue was purified by
+
m/z (MS) 134 [M] .
Supporting Information Available: Experimental details and
characterization of products. This material is available free of
charge via the Internet at http://pubs.acs.org.
(
14) Denmark, S. E.; Butle, C. R. Org. Lett. 2006, 8, 63–66.
JO900290T
J. Org. Chem. Vol. 74, No. 9, 2009 3605