Functional group compatible palladium-catalyzed cross-coupling reactions between aryllithium and aryl halide mediated by a five-membered cyclic silyl ether

Article abstract of DOI:10.1246/bcsj.79.492

A functional group compatible palladium-catalyzed cross-coupling reaction between aryllithiums and aryl halides mediated by a five-membered cyclic silyl ether as a precursor for an activated arylsilane has been developed. The reaction proceeds under mild conditions without the addition of a fluoride salt or a base to activate the silyl reagent.

Full text of DOI:10.1246/bcsj.79.492

492 Short Articles
Bull. Chem. Soc. Jpn. Vol. 79, No. 3, 492–494 (2006)
Li
OLi
SiMe2
R1
O
Functional Group Compatible
Palladium-Catalyzed Cross-
Coupling Reactions between
Aryllithium and Aryl Halide
Mediated by a Five-Membered
Cyclic Silyl Ether
SiMe2
THF, 0 °C-rt
1
2
R1
I
R2
CuI
R2
R1
[PdCl2(PPh3)2]
THF-DMF
80 °C
Scheme 1.
Table 1. Effects of Solvent and Copper ReagentaÞ
Eun-Cheol Son, Hayato Tsuji,
y
ꢀ
Tomoyuki Saeki, and Kohei Tamao
Copper reagent
(mol amount)cÞ
Yield of biaryl
/%bÞ
Entry
Solvent
International Research Center for Elements Science
(IRCELS), Institute for Chemical Research,
Kyoto University, Uji, Kyoto 611-0011
1
2
3
4
5
THF
CuI (1)
CuI (1)
CuI (1)
CuI (1)
CuI (0.5)
None
CuI (1)
CuCl (1)
CuBr (1)
CuCN (1)
25
60
80
87eÞ
72fÞ
0
trace
10
THF/MeCN
THF/DMSO
THF/DMF
THF/DMF
THF/DMF
THF/DMF
THF/DMF
THF/DMF
THF/DMF
Received October 5, 2005; E-mail: tamao@riken.jp
6
7dÞ
8
A functional group compatible palladium-catalyzed
cross-coupling reaction between aryllithiums and aryl hal-
ides mediated by a five-membered cyclic silyl ether as a pre-
cursor for an activated arylsilane has been developed. The
reaction proceeds under mild conditions without the addition
of a fluoride salt or a base to activate the silyl reagent.
9
10
52
trace
a) R1 ¼ H, R2 ¼ 4-NO2. Reaction time = 3 h unless other-
wise noted. b) GC yield. c) Mol amount of the copper reagent
is based on the cyclic ether 1. d) Without Pd catalyst. e) Re-
action time = 2 h. f) Isolated yield.
The transition metal-catalyzed cross-coupling reactions be-
tween organometallic reagents and organic halides or pseudo-
halides have been extensively studied because of their versatil-
ity for carbon–carbon bond formation.1 Among these organo-
metallic nucleophiles, organosilicon compounds are some of
the most useful reagents in the palladium-catalyzed cross-cou-
pling reactions2–4 as long as the proper activation of the silicon
carbon bond is achieved; the silicon-based cross-coupling reac-
tions require the formation of hypercoordinate silicon species
to promote the transmetallation of the organic group from the
silicon to the transition-metal center. For this purpose, a fluo-
ride or a strong base5 has been used for the activation. Many
attempts have recently been made to achieve milder reaction
conditions such as fluoride-free or a strong base-free silicon-
based cross-coupling reactions.6,7 Since the silicon center of the
substrates must have at least one electronegative atom or group
such as F, Cl, or OR for the effective formation of the hyper-
coordinate silicon species, less reactive tetraorganosilicon com-
pounds have been rarely employed in the transition metal-cat-
alyzed coupling reactions except for a few reactions,8–10 despite
their high stability and high compatibility with other chemical
species, as well as their negligible toxicity. We now report the
biaryl synthesis between aryllithiums and aryl halides mediated
by a five-membered cyclic silyl ether, 2,2-dimethyl-1-oxa-2-
silaindan, as a precursor for the activated tetraorganosilicon
nucleophiles shown in Scheme 1.11 The present method allows
aryl halides to possess various functional groups.
As shown in Scheme 1, the arylsilane nucleophile 2 was
generated in situ from 1 and an aryllithium (R1-C6H4Li), to
which copper(I) iodide and an aryl iodide (R2-C6H4I) together
with DMF and a 0.02 molar amount of [PdCl2(PPh3)2] were
successively added. Upon heating at 80 ꢁC for 2–24 h, the cor-
responding cross-coupled biaryl compounds were obtained in
good yield.12 It should be noted that the reaction smoothly pro-
ceeds without the addition of an external fluoride or even a
weak base as an activator.
The effects of the solvent and copper reagent are listed in
Table 1. Solvent effect (Entries 1–4): The coupling reaction
is promoted by the addition of a polar co-solvent. Dimethyl-
formamide (DMF) afforded the best result. Copper(I) reagent
effect (Entries 4–10): A stoichiometric amount of CuI is nec-
essary for the effective cross-coupling reactions.
Based on these results, we have postulated a mechanism
for the reaction (Scheme 2). The lithium phenoxide species 2
is converted to the copper phenoxide 3, which subsequently
undergoes an intramolecular transmetallation of the aryl group
(Ar1) from silicon to copper. This transmetallation is supposed
to be promoted by the intramolecular coordination of oxygen
to the silicon center by placing these atoms in close proximity.
In addition, this step would require a highly polar solvent
as reported by Hosomi et al.9a,b Indeed, the reaction in THF
(Table 1, Entry 1) afforded a large amount of the phenol deriv-
ative generated by hydrolysis of the unreacted intermediate
2 or 3, together with a small amount of the cross-coupled
product.
y Present address: RIKEN Frontier Research System, 2-1
Hirosawa, Wako, Saitama 351-0198
Published on the web March 8, 2006; DOI 10.1246/bcsj.79.492

Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
Ó 2006 The Chemical Society of Japan
493
Table 2. Reactions with Functionalized Aryl Iodides
[Cu]
O
CuI
[Cu] Ar1
product
2
Ar1
R1
R2
Time/h
Yield of biaryl/%aÞ
SiMe2
Entry
1
2
3
4
5
6
7
8
9
10
11
12
13
H
H
H
H
H
H
H
H
H
4-NO2
4-NO2
4-CN
4-COMe
4-CO2Et
4-F
2
6
3
3
3
3
3
5
5
87
52
87
94
81
89
71
77
56
44
67
65
52
3
bÞ
Scheme 2.
PhLi
THF
O
OLi
SiMe2
SiMe2
4-Me
0 °C-rt
4-OMe
2-OMe
2,4,6-Me3
4-NO2
4-NO2
4-NO2
4
5
H
5
O2N
I
OMe
CF3
12
24
17
O2N
[PdCl2(PPh3)2]
cÞ
—
CuI
THF-DMF
80 °C
Not obtained
a) Isolated yield. b) The aryl bromide was used. c) 2-Thienyl-
lithium was used instead of phenyllithium.
Scheme 3.
and DMF were purchased as dried solvents, and other chemicals
were used as received.
To confirm the significance of such an intramolecular acti-
Preparation of 2,2-Dimethyl-1-oxa-2-silaindan (1). The cy-
clic ether 1 is a known compound.14 We have developed our own
preparative procedure as shown in the following scheme.
vation, we have tested two types of other silyl substrates. First,
trimethylsilylbenzene was used as a silyl nucleophile to at-
tempt an intermolecular activation using a mixture of lithium
phenoxide and CuI. This reaction did not afford the desired
biaryl compound under similar reaction conditions.13 Second,
a six-membered cyclic silyl ether 4 was used as a precursor
of the arylsilane nucleophile 5 (Scheme 3). This reaction
affords not the desired cross-coupled product, but the benzyl
alcohol derivative due to hydrolysis of the unreacted inter-
mediate 5. These results clearly demonstrate the advantage
of the five-membered cyclic silyl ether 1 suitable for the intra-
molecular activation in the intermediate 3.
The cross-coupling reactions of the aryllithium with various
functionalized aryl iodides in the presence of 1 have been ex-
amined, and the results are summarized in Table 2. As expect-
ed, aryl iodides with a nitro, cyano group, ester, and acyl group
afforded the corresponding cross-coupled product in high yield
(Entries 1 and 3–5). Aryl iodides with an electron-donating
group and an aryl bromide require a somewhat longer reaction
time (Entries 2, 7, and 8). Sterically hindered aryl iodides re-
sulted in lower yields (Entries 9 and 10). Aryllithiums with
electron-donating and electron-withdrawing groups as well as
thienyllithium also afford the corresponding biaryl compounds
in moderate yields (Entries 11–13).
[PdCl2(PPh3)2]
nOTMS
+ (i-PrO)Me2SiCH2MgCl
THF, rt
I
7
6 (n = 0)
9 (n = 1)
Amberlyst 15
MeCN, rt
ð1Þ
nOTMS
SiMe2
nO
SiMe2
1 (n = 0)
4 (n = 1)
or TFA
MeOH, 0 °C
Oi-Pr
8 (n = 0)
10 (n = 1)
1-[(Isopropoxy)dimethylsilyl]methyl-2-trimethylsiloxyben-
zene (8): To a solution of 1-iodo-2-trimethylsiloxybenzene (6)
(33.5 g, 115 mmol) and [PdCl2(PPh3)2] (2.42 g, 3.4 mmol) in THF
(50 mL) was added the Grignard reagent 7,15 which was prepared
from the corresponding halide (23 mL, 124 mmol), magnesium
(3.35 g, 138 mmol), and THF (100 mL) at room temperature, and
the mixture was stirred for 10 h. After quenching with water, the
mixture was extracted with Et2O. The combined organic layer
was washed with brine and dried over MgSO4. After filtration
and evaporation of the solvent, the residue was subjected to vacu-
um distillation to afford 8 (32.5 g, 110 mmol; 95% yield) as color-
1
less oil; bp 78–80 ꢁC/53 Pa. H NMR (C6D6) ꢀ 0.22 (s, 6H), 0.23
(s, 9H), 1.17 (d, J ¼ 6:0 Hz, 6H), 2.35 (s, 2H), 3.97 (sept, J ¼ 6:0
Hz, 1H), 6.82 (d, J ¼ 7:5 Hz, 1H), 6.91 (dd, J ¼ 7:5, 7.2 Hz, 1H),
6.99 (dd, J ¼ 7:5, 7.2 Hz, 1H), 7.16 (d, J ¼ 7:5 Hz, 1H). 13C NMR
(C6D6) ꢀ ꢂ0:9, 0.7, 21.6, 26.3, 65.3, 118.6, 121.7, 125.6, 127.9,
130.6, 152.9. 29Si NMR ꢀ 12.0, 17.7. MS (EI, 70 eV) m=z (%) 296
(Mþ, 51), 253 (100). Anal. Calcd for C15H28O2Si2: C, 60.75; H,
9.52%. Found: C, 60.60; H, 9.73%.
2,2-Dimethyl-1-oxa-2-silaindan (1): To a suspension of Am-
berlyst 15 (0.10 g) in MeCN (10 mL) was added 8 (1.48 g, 5.0
mmol) at room temperature, and the resulting mixture was stirred
for 2 h. Amberlyst was removed by decantation and rinsed with
THF. The combined organic phase was concentrated under re-
duced pressure, and subjected to bulb-to-bulb distillation to afford
1 (0.52 g, 3.2 mmol; 63% yield) as colorless oil; bp 105 ꢁC/160
Pa. 1H NMR (C6D6) ꢀ 0.10 (s, 6H), 1.80 (s, 2H), 6.87 (dd, J ¼
6:9, 7.2 Hz, 1H), 7.07 (dd, J ¼ 7:2, 7.2 Hz, 1H), 7.11 (d, J ¼
6:9 Hz, 1H), 7.23 (d, J ¼ 7:2 Hz, 1H).
In summary, we have developed a functional group compat-
ible palladium-catalyzed cross-coupling reaction between aryl-
lithium and aryl halide using 2,2-dimethyl-1-oxa-2-silaindan
(1) as a precursor for an activated arylsilane. The reactions
proceed well in the presence of CuI under mild conditions
without the addition of an external fluoride or even a weak
base to activate the silyl reagent.
Experimental
All reactions were performed under argon. 1H
General.
(300 MHz) and 13C (67.9 MHz) NMR spectra were recorded on
a Varian Mercury 300 and a JEOL EX-270 spectrometer, respec-
1
tively. H and 13C chemical shifts are referenced to internal ben-
zene-d6 (1H, ꢀ 7.20 and 13C, ꢀ 128.0 ppm). Column chromatogra-
phy was performed using Kieselgel (70–230 mesh, Merck). THF

494 E.-C. Son et al.
Bull. Chem. Soc. Jpn. Vol. 79, No. 3 (2006)
Preparation of 3,3-Dimethyl-2-oxa-3-sila-1,2,3,4-tetrahydro-
naphthalene (4). The cyclic ether 416 was prepared in a similar
manner to that described for 1.
Ministry of Education, Culture, Sports, Science and Technolo-
gy, Japan. We also thank Prof. F. Ozawa for valuable discus-
sions.
1-[(Isopropoxy)dimethylsilyl]methyl-2-trimethylsiloxymeth-
ylbenzene (10): To a solution of 1-iodo-2-trimethylsiloxymethyl-
benzene (9) (5.17 g, 16.9 mmol) and [PdCl2(PPh3)2] (0.35 g, 0.5
mmol) in THF (10 mL) was added the Grignard reagent 7, which
was prepared from the corresponding halide (3.5 mL, 19.2 mmol),
magnesium (0.49 g), and THF (20 mL), at room temperature, and
stirred for 4 h. After quenching with water, the mixture was ex-
tracted with Et2O three times, and the combined organic layer
was washed with brine and dried over MgSO4. The remaining
crude product was purified by silica gel column chromatography
(hexane/AcOEt = 4/1 as an eluent) to afford the title compound
(5.06 g, 16.3 mmol; 96% yield) as a colorless oil. 1H NMR (C6D6)
ꢀ 0.11 (s, 6H), 0.20 (s, 9H), 1.08 (d, J ¼ 6:0 Hz, 6H), 2.78 (s, 2H),
3.82 (sept, J ¼ 6:0 Hz, 1H), 4.85 (s, 2H), 7.06–7.18 (m, 3H), 7.61
(m, 1H). 13C NMR (C6D6) ꢀ ꢂ0:9, ꢂ0:1, 23.8, 26.2, 63.8, 65.5,
124.8, 127.3, 128.0, 129.5, 137.3, 138.1. 29Si NMR (C6D6) ꢀ 11.6,
17.7. MS (EI, 70 eV) m=z (%) 310 (Mþ, 0.2), 267 (0.1), 237 (12),
75 (100). Anal. Calcd for C16H30O2Si2: C, 61.88; H, 9.74%.
Found: C, 61.69; H, 9.80%.
References
1
a) Metal-Catalyzed Cross-Coupling Reactions, ed. by F.
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2
For reviews, see: a) Y. Hatanaka, T. Hiyama, Synlett 1991,
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3
J. Yoshida, K. Tamao, H. Yamamoto, T. Kakui, T. Uchida,
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5
a) E. Hagiwara, K. Gouda, Y. Hatanaka, T. Hiyama, Tetra-
3,3-Dimethyl-2-oxa-3-sila-1,2,3,4-tetrahydronaphthalene (4):
To a solution of 10 (4.2 g, 13.5 mmol) in MeOH (45 mL) was add-
ed trifluoroacetic acid (0.01 mL, 0.14 mmol) at 0 ꢁC. The reaction
mixture was stirred at 0 ꢁC for 0.5 h and at room temperature for
1 h. The mixture was concentrated under reduced pressure and pu-
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10.7 mmol; 80% yield) as colorless oil; bp 120 ꢁC/60 Pa. 1H NMR
(C6D6) ꢀ 0.08 (s, 6H), 1.86 (s, 2H), 4.76 (s, 2H), 6.91 (d, J ¼ 7:2
Hz, 1H), 7.02 (dd, J ¼ 7:2, 7.2 Hz, 1H), 7.07 (d, J ¼ 7:2 Hz, 1H),
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7
Intramolecular coordination-assisted activation: M.
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a) H. Ito, H. Sensui, K. Arimoto, K. Miura, A. Hosomi,
8
9
A Typical Procedure for Biaryl Synthesis. To a solution of 1
(918 mg, 5.6 mmol) in THF (9.0 mL) was added a dibutyl ether
solution of phenyllithium (2.04 mol Lꢂ1, 2.75 mL, 5.6 mmol) at
0 ꢁC. The reaction mixture was stirred at 0 ꢁC for 10 min and at
room temperature for 20 min. To the resulting silicon reagent 2
was added CuI (1.07 g, 5.6 mmol) in one portion, and the resulting
dark brown mixture was stirred at room temperature for 10 min.
To the mixture were added [PdCl2(PPh3)2] (78 mg, 0.11 mmol),
4-iodonitrobenzene (1.27 g, 5.1 mmol), and DMF (3.0 mL). The
resulting mixture was stirred at 80 ꢁC for 2 h. After quenching
with water, the mixture was filtered and the filtrate was extracted
with Et2O three times. The combined organic layer was washed
with brine and dried over MgSO4. After filtration and evaporation
of the solvent, the residue was subjected to silica gel column chro-
matography (hexane/AcOEt = 4/1 as an eluent) to afford 4-nitro-
biphenyl (880 mg, 4.4 mmol, 87% yield based on 4-iodonitroben-
zene) as a yellow solid.
Chem. Lett. 1997, 639. b) H. Ito, A. Hosomi, J. Synth. Org. Chem.,
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11 While developing the present work in our laboratory,
Nakao, Hiyama, and their co-workers have reported tetraorgano-
silicon-based cross-coupling reactions using a similar five-mem-
bered cyclic silyl ether: Y. Nakao, H. Imanaka, A. K. Sahoo, A.
Yada, T. Hiyama, J. Am. Chem. Soc. 2005, 127, 6952.
12 The cyclic silyl ether 1 could not be recovered as a pure
component after the reaction.
13 Hosomi et al. also reported that a reaction of trimethylsilyl-
benzene and 4-iodotoluene in the presence of CuI did not afford
the cross-coupled product. See Ref. 9a.
14 A. J. Stern, J. S. Swenton, J. Org. Chem. 1989, 54, 2953.
15 K. Tamao, N. Ishida, Y. Ito, M. Kumada, Org. Synth. 1990,
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This work was supported by Grants-in-Aid for ‘‘Joint Pro-
ject of Chemical Synthesis Core Research Institutions’’ and
COE Research on ‘‘Elements Science’’ No. 12CE2005 from
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