An efficient synthesis of arylcyclobutenes via cross-coupling of aryl halides with 1-(Tri-n-butylstannyl)cyclobutene

Article abstract of DOI:10.1016/S0040-4020(00)00350-1

1-Tri-n-butylstannylcyclobutene, obtained from 1-bromocyclobutene by lithium/bromine exchange and transmetalation with chloro-tri-n-butylstannane, could be effectively converted with aryl halides into 1-arylcyclobutenes by the Stille cross-coupling proced

Full text of DOI:10.1016/S0040-4020(00)00350-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4249±4252
An Ef®cient Synthesis of Arylcyclobutenes via Cross-Coupling of
Aryl Halides with 1-(Tri-n-butylstannyl)cyclobutene
*
Jing Feng and GuÈnter Szeimies
È
È
Institut fur Chemie der Humboldt-Universitat zu Berlin, Hessische Str. 1-2, D-10115 Berlin, Germany
Dedicated to Professor Rolf Huisgen on the occasion of his 80th birthday
Received 17 April 2000; accepted 28 April 2000
AbstractÐ1-Tri-n-butylstannylcyclobutene, obtained from 1-bromocyclobutene by lithium/bromine exchange and transmetalation with
chloro-tri-n-butylstannane, could be effectively converted with aryl halides into 1-arylcyclobutenes by the Stille cross-coupling procedure.
Hetero-aryl halides like 2-bromopyridine and 2-iodothiophene were also successfully coupled, and in 1,3,5-tribromobenzene, 1,2,4,5-
tetrabromobenzene and hexabromobenzene all bromine atoms could be exchanged. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
Table 1 shows the results.
Although several strategies for the synthesis of cyclobutenes
have been developed in the past,1 this class of compounds is
generally not easily accessible. In recent years, some routes
to cyclobutenes via cycloalkylation have also been
described.2 However, the general applicability of these
methods is limited. Herein we report on a convenient and
general synthesis of arylcyclobutenes via the Stille reaction3
of aryl halides with 1-tri-n-butylstannylcyclobutene (3). We
have recently shown that 1-bromobicyclo[1.1.0]butane (1)
is obtained from 1,1-dibromo-2-chlormethylcyclopropane
and methyllithium.4 The conversion of 1 into 1-bromo-
cyclobutene (2) is achieved by acid-catalyzed rearrange-
ment. Compound 2 has also been used as a precursor for
an ef®cient synthesis of cyclobutanone.5
In addition to 4a±4m, 4-iodoaniline and 4-iodo-
(N,N)dimethylaniline were also treated with 3, but the
expected products were not formed. Obviously an amino
group is not tolerated within the catalytic cycle of this
reaction.7 It is interesting to note that electron acceptor
substituents (p-NO2, m-CF3, p-COCH3) and electron donor
substituents (p-OCH3) give comparable results.
Having demonstrated that 3 reacts well with aryl mono-
halides, the dihalides 6a±d were treated with two
equivalents of 3 in the presence of 10 mol percent of
Pd(PPh3)4, again in DMF at 658C. Within 18±24 h, good
1-Tri-n-butylstannylcyclobutene (3) as cross-coupling part-
ner was obtained from 2 with tert-butyllithium in ether
followed by transmetalation with chlorotri-n-butylstannane.
In Scheme 1 the synthesis of 3 is depicted.
Results
With the convenient route to 3, effective cross-coupling
reactions with a wide variety of aryl halides were possible.
The reactions of 3 were carried out with iodides and
bromides 4 in DMF at 658C with Pd(PPh3)4 as a catalyst.6
Approximately 5 mol percent of the catalyst were used (see
Scheme 2). The corresponding 1-arylcyclobutenes 5 were
isolated in good yields after reaction times of 18±48 h.
Scheme 1.
Keywords: Stille coupling; cyclobutenes; palladium catalysis.
* Corresponding author. Tel.: 130-20937365; fax: 130-20936940;
e-mail: guenter-szeimies@rz.hu-berlin.de
Scheme 2.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00350-1

4250
J. Feng, G. Szeimies / Tetrahedron 56 (2000) 4249±4252
Table 1. Arylcyclobutenes 5 from 3 and arylhalides 4
4, 5
Aryl group of 4 and 5
4-tolyl
3-tolyl
2-tolyl
4-anisyl
3-anisyl
2-thioanisyl
3-(tri¯uoro-methyl)phenyl
4-nitrophenyl
4-(trimethyl-silyl)phenyl
4-acetylphenyl
1-naphthyl
Halogen of 4
Reaction time (h)
% Yield of 5
a
b
c
d
e
f
g
h
i
I
I
I
I
Br
I
Br
I
Br
I
I
Br
I
24
24
24
24
48
24
18
24
18
48
24
24
24
94
85
86
87
98
84
96
98
84
98
71
97
88
j
k
l
2-pyridyl
2-thienyl
m
yields of 7a±d could be isolated. The results are shown in
Scheme 3.
The successful conversion of 6a±d into the coupling
products 7a±d indicated that even higher halogenated
benzenes could be used for the Stille coupling. Indeed, the
ef®ciency of this cross-coupling reaction could be demon-
strated using 1,3,5-tribromobenzene, 1,2,4,5-tetrabromo-
benzene and hexabromobenzene as starting materials. The
reactions of 3 with these halides were carried out as
described above, applying 6, 8, and, respectively 12 mol
percent of Pd(PPh3)4 as a catalyst. The arylcyclobutenes 8,
9 and 10 were isolated in 74, 54 and 52% yield (see
Scheme 4).
Hexa(1-cyclobutenyl)benzene (10) is a waxy solid, which
readily polymerized on contact with air. The 13C NMR
spectrum of 10 at room temperature showed 5 signals,
indicating that the barrier of rotation around the bond
connecting the benzene ring with the cyclobutene unit is
easily surmounted at ambient temperature.
Scheme 3.
In conclusion, we have developed an ef®cient synthesis of
arylcyclobutenes. Starting materials are readily available,
the procedure is simple, the reaction conditions are mild
and the yields are high.
Experimental
General
All reactions were carried out under nitrogen. Ether was
freshly distilled from sodium, dimethylformamide (DMF)
from calcium hydride. Flash chromatography was
1
performed on silica gel 230±400 mesh. H NMR spectra
were recorded on a Bruker DPX 300 at 300 MHz, 13C
NMR on the same instrument at 75 MHz, using CDCl3 as
solvent. Mass spectra were obtained on a Finnigan MAT 95
SQ apparatus (70 eV).
1-Tri-n-butylstannylcyclobutene (3). tert-Butyllithium in
hexane (11 ml, 1.7 M, 18.7 mmol) was added dropwise at
2728C to 1-bromocyclobutene (1) (1.33 g, 10.0 mmol) in
ether (15 ml). After 2 h at 08C, chlorotri-n-butyltin (3.25 g,
10.0 mmol) was added dropwise, the mixture was allowed
to warm to room temperature and stirred for 2 h. The
Scheme 4.

J. Feng, G. Szeimies / Tetrahedron 56 (2000) 4249±4252
4251
mixture was quenched with saturated NH4Cl solution,
extracted with water and the ether layer dried over
anhydrous MgSO4. Removal of the solvent in vacuo and
puri®cation by column chromatography (petroleum ether)
afforded 3 (2.47 g, 72%) as a colorless liquid.
2-(1-Cyclobutenyl)thioanisole (5f). Colorless oil, yield
84%. H NMR (CDCl3): d 2.50 (s, 3H), 2.58 (m, 2H),
1
2.92 (m, 2H), 6.51 (broad s, 1H), 7.14±7.22 (m, 4H). 13C
NMR (CDCl3): d 15.2 (CH3), 27.0 (CH2), 30.7 (CH2),
124.1, 124.2, 126.9, 127.5 (CH), 133.7 (CH), 137.7 (Cq),
144.5 (Cq). MS (EI): m/z (%) 176 (M1, 40), 161 (100), 128
(50), 115 (15), 89 (8). HRMS (C12H11S) calcd:176.0651,
found: 176.6450.
1H NMR (CDCl3): d 0.86±0.91 (m, 15H), 1.28±1.32 (m,
6H), 1.45±1.51 (m, 6H), 2.62 (m, 2H), 2.86 (m, 2H), 6.44
(broad s, 1H). 13C NMR (CDCl3): d 9.3 (CH2), 13.7 (CH3),
27.3 (CH2), 29.2 (CH2), 35.2 (CH2), 37.3 (CH2), 151.7 (CH),
155.0 (Cq). MS (EI): m/z (%) 343 (M12H, 4), 287 (100),
231 (56), 177 (60), 121 (28). HRMS (C16H32Sn) calcd:
343.1447, found: 343.1448.
4-(1-Cyclobutenyl)nitrobenzene (5h). Yellow solid, yield
98%. 1H NMR (CDCl3): d 2.52 (m, 2 H), 2.77 (m, 2 H), 6.47
(broad s, 1H), 7.35±8.11 (m, 4H). 13C NMR (CDCl3): d 26.8
(CH2), 28.7 (CH2), 123.8, 124.7 (CH), 133.2 (CH), 140.7
(Cq), 144.5 (Cq). MS (EI): m/z (%) 175 (M1, 60), 158 (65),
128 (100), 101 (25), 51 (30). HRMS (C10H9NO2) calc:
175.0632, found: 175.0632.
General procedure for the cross-coupling reaction
Under nitrogen atmosphere, 0.50 mmol of 3 and 0.25 mmol
of the aryl halide were dissolved in 3 ml of DMF followed
by addition of 5.0 mol% of Pd(PPh3)4 (based on aryl halide).
The resulting mixture was stirred at 658C for 18±48 h. Ether
(20 ml) was added, and the solution was washed with an
aqueous KF solution and with brine. The organic layer was
dried with anhydrous MgSO4. After concentration of the
organic solution, the oily residue was subjected to a silica
gel chromatography using a mixture of petroleum ether and
ethyl acetate as eluent. In all cases, the excess of 3 was
found in the ®rst fraction. All fractions containing the
product were combined, the solvent removed in vacuo and
the remaining oil was characterized by 1H NMR, 13C NMR,
by MS and HRMS. The oils 5h, 5j, 7a, 7c, 8, 9, and 10
solidi®ed slowly to a waxy mass.
4-(1-Cyclobutenyl)trimethylsilylbenzene (5i). Colorless
oil, yield 84%. H NMR (CDCl3): d 0.26 (s, 9H), 2.52 (m,
1
2H), 2.84 (m, 2H), 6.30 (broad s, 1H), 7.38±7.50 (m, 4H).
13C NMR (CDCl3): d 21.2 (CH3), 26.3 (CH2), 28.7 (CH2),
123.4 (CH), 127.5, 133.3 (CH), 134.9 (Cq), 139.6 (Cq),
146.4 (Cq). MS (EI): m/z (%) 202 (M1, 100), 159 (4), 128
(4), 73 (8). HRMS (C13H18Si): calcd: 202.1177, found:
202.1176.
4-(1-Cyclobutenyl)acetophenone (5j). Colorless waxy
solid, yield 98%. H NMR (CDCl3): d 2.56 (m, 2H), 2.58
1
(s, 3H), 2.82 (m, 2H), 6.45 (broad s, 1H), 7.38 (m, 2H), 7.92
(m, 2H). 13C NMR (CDCl3): d 26.5 (CH2), 26.6 (CH3), 28.7
(CH2), 124.1, 128.5, 130.9 (CH), 135.7, 139.1, 145.4, 197.6
(Cq). MS (EI): m/z (%) 172 (M1, 55), 147 (35), 129 (100),
115 (20), 77 (20), 51 (10). HRMS (C12H12O) calcd:
172.0883, found: 172.0882.
1H and 13C NMR spectra of 4-(1-cyclobutenyl)toluene (5a),
4-(1-cyclobutenyl)anisole (5d) and 1-(1-cyclobutenyl)-3-
(tri¯uoromethyl)benzene (5g) were identical to the reported
literature values.8,9
1-(1-Cyclobutenyl)naphthalene (5k). Colorless oil, yield
1
71%. H NMR (CDCl3): d 2.66 (m, 2H), 3.04 (m, 2H),
6.54 (broad s, 1H), 7.41±8.46 (m, 7H). 13C NMR
(CDCl3): d 27.0 (CH2), 31.3 (CH2), 124.4 (CH), 125.2
(CH), 126.3 (CH), 128.0 (CH), 128.6 (CH), 134.1 (Cq),
137.4 (Cq), 145.6 (Cq). MS (EI): m/z (%) 180 (M1, 95),
152 (100), 127 (70), 89 (35), 51 (15). HRMS (C14H12)
calcd: 180.1017, found: 180.1023.
3-(1-Cyclobutenyl)toluene (5b). Colorless oil, yield 85%.
1H NMR (CDCl3): d 2.34 (s, 3H), 2.52 (m, 2H), 2.79 (m,
2H), 6.27 (broad s, 1H), 7.16 (m, 4H). 13C NMR (CDCl3): d
21.3 (CH3), 26.2 (CH2), 28.7 (CH2), 121.3, 124.8, 126.9,
128.3, 134.1(CH), 134.9 (Cq), 137.7 (Cq), 146.5 (Cq). MS
(EI): m/z (%) 144 (M1, 60), 129 (100), 115 (40), 91 (10).
HRMS (C11H12) calcd: 144.0939, found: 144.0940.
2-(1-Cyclobutenyl)pyridine (5l). Colorless oil, yield 97%.
1H NMR (CDCl3): d 2.50 (m, 2H), 2.84 (m, 2H), 6.63 (broad
s, 1H), 7.05±8.51 (m, 4H). 13C NMR (CDCl3): d 26.5
(CH2), 28.6 (CH2), 132.4 (CH), 119.1, 121.9, 136.1, 149.4
(CH), 146.4 (Cq), 152.8 (Cq). MS (EI): m/z (%) 130 (M12H,
100), 104 (6), 78 (4). HRMS (C9H9N) calcd: 130.0657
(M12H), found: 130.0661.
2-(1-Cyclobutenyl)toluene (5c). Colorless oil, yield 86%.
1H NMR (CDCl3): d 2.40 (s, 3H), 2.55 (m, 2H), 2.89 (m,
2H), 6.18 (broad s, 1H), 7.15±7.22 (m,4H). 13C NMR
(CDCl3): d 21.8 (CH3), 26.8 (CH2), 30.6 (CH2), 125.7
(CH), 126.1, 127.4, 130.5, 131.2 (CH), 133.5 (Cq), 136.5
(Cq), 146.4 (Cq). MS (EI): m/z (%) 144 (M1, 56), 129 (100),
115 (50), 91 (4). HRMS (C11H12) calcd: 144.0939, found:
144.0942.
2-(1-Cyclobutenyl)thiophene (5m). Colorless oil, yield
88%. 5m decomposed slowly during the recording of the
1
NMR spectra. H NMR (CDCl3): d 2.49 (m, 2H), 2.74 (m,
3-(1-Cyclobutenyl)anisole (5e). Colorless oil, yield 98%.
1H NMR (CDCl3): d 2.52 (m, 2H), 2.78 (m, 2H), 3.81 (s,
3H), 6.29 (broad s, 1H), 6.87±7.20 (m, 4H). 13C NMR
(CDCl3): d 26.2 (CH2), 28.7 (CH2), 55.2 (CH3), 109.5
(CH), 113.1, 116.8, 127.6, 129.3 (CH), 136.4 (Cq), 146.2
(Cq), 159.6 (Cq). MS (EI): m/z (%) 160 (M1, 100), 145 (28),
129 (72), 115 (40), 102 (20), 91 (18). HRMS (C11H12O)
calcd: 160.0888, found: 160.0888.
2H), 5.97 (broad s, 1H), 6.86±7.08 (m, 3H). 13C NMR
(CDCl3): d 27.3 (CH2), 30.2 (CH2), 123.3 (CH), 124.4,
126.0, 127.2 (CH), 139.3 (Cq), 140.2 (Cq). MS (EI): m/z
(%) 136 (M1, 96), 108 (48), 97 (28), 69 (8). HRMS calcd:
136.0346, found: 136.0344.
1,4-Di(1-cyclobutenyl)benzene (7a). Waxy solid, yield
93%. H NMR (CDCl3): d 2.53 (m, 4H), 2.79 (m, 4H),
1

4252
J. Feng, G. Szeimies / Tetrahedron 56 (2000) 4249±4252
6.27 (broad s, 2H), 7.29 (s, 4H). 13C NMR (CDCl3): d 26.3
(CH2), 28.7 (CH2), 124.2 (CH), 127.1 (CH), 137.3 (Cq),
146.2 (Cq). MS (EI): m/z (%) 182 (M1, 60), 153 (34), 129
(100), 115 (20), 105 (6). HRMS (C14H14) calcd: 182.1096,
found: 182.1097.
1,2,3,4,5,6-Hexa(1-cyclobutenyl)benzene (10). Colorless
1
solid, yield 52%. H NMR (CDCl3): d 2.45 (m, 12H),
2.71 (m, 12H), 5.91 (broad s, 6H). 13C NMR (CDCl3): d
27.4 (CH2), 34.3 (CH2), 133.0 (CH), 133.8 (Cq), 146.7 (Cq).
MS (EI): m/z (%) 390 (M1, 4), 333 (24), 306 (100), 263
(60), 226 (10), 138 (20). HRMS (C30H30) calcd 390.2348,
found 390.2349.
1,2-Di(1-cyclobutenyl)benzene (7b). Colorless oil, yield
1
98%. H NMR (CDCl3): d 2.50 (m, 4H), 2.86 (m, 4H),
6.20 (broad s, 2H), 7.20 (m, 4H). 13C NMR (CDCl3): d
26.7 (CH2), 31.2 (CH2), 127.1 (CH), 127.5 (CH), 131.4
(CH), 133.6 (Cq), 146.7 (Cq). MS (EI): m/z (%) 181
(M12H, 16), 167 (100), 153 (60), 128 (18), 115 (20).
HRMS (C14H14) calcd: 181.1017 (M12H), found:
181.1010.
Acknowledgements
We gratefully acknowledge the ®nancial support of the
Deutsche Forschungsgemeinschaft and the Fonds der
È
Chemischen Industrie. We thank Dr G. Hohne, Technische
2,6-Di(1-cyclobutenyl)pyridine (7c). Yellow solid, yield
95%. H NMR (CDCl3): d 2.48 (m, 4H), 2.81 (m, 4H),
È
Universitat Berlin, for the mass spectra.
1
6.53 (broad s, 2H), 7.04±7.50 (m, 3H). 13C NMR
(CDCl3): d 26.5 (CH2), 28.8 (CH2), 117.5 (CH), 132.6
(CH), 136.3 (CH), 146.7 (Cq), 152.6 (Cq). MS (EI): m/z
(%) 182 (M12H, 100), 154 (20), 129 (18), 102 (20), 77
(16). HRMS (C13H13N) calcd: 182.0969 (M12H), found:
182.0964.
References
1. For a recent review, see: Houben-Weyl, Methoden der
organischen Chemie; de Meijere A., Ed.; Georg Thieme Verlag:
Stuttgart, 1997; Vol. E 17f, Chapter 8.
2,5-Di(1-cyclobutenyl)thiophene (7d). Colorless oil, yield
95%. 1H NMR (CDCl3): d 2.49 (m, 4H), 2.72 (m, 4H), 5.95
(broad s, 2H), 6.70 (m, 2H). 13C NMR (CDCl3): d 27.3
(CH2), 30.1 (CH2), 123.6 (CH), 126.3 (CH), 140.2 (Cq),
148.1 (Cq). MS (EI): m/z (%) 188 (M1, 100), 160 (20),
148 (24), 135 (20), 115 (28), 91 (10). HRMS (C12H12S)
calcd: 188.0659, found: 188.0654.
2. (a) Negishi, E.; Liu, F.; Choueriy, D.; Mohamud, M. M. J. Org.
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1,3,5-Tri(1-cyclobutenyl)benzene (8). Colorless solid,
1
yield 74%. H NMR (CDCl3): d 2.53 (m, 6H), 2.80 (m,
6H), 6.31 (broad s, 3H), 7.19 (s, 3H). 13C NMR (CDCl3):
d 26.2 (CH2), 28.8 (CH2), 119.0 (CH), 127.6 (CH), 135.0
(Cq), 146.2 (Cq). MS (EI): m/z (%) 234 (M1, 64), 205 (20),
183 (30), 165 (80), 132 (64), 105 (38), 84 (54). HRMS
(C18H18) calcd: 234.1408, found: 234.1406.
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6. We have observed that Pd(PPh3)2Cl2 could also be used as a
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1,2,4,5-Tetra(1-cyclobutenyl)benzene (9). Colorless solid,
yield 54%. 1H NMR (CDCl3): d 2.50 (m, 8H), 2.85 (m, 8H),
6.20 (broad s, 4H), 7.03 (s, 2H). 13C NMR (CDCl3): d 26.7
(CH2), 31.2 (CH2), 126.7 (CH), 131.6 (CH), 132.3 (Cq),
146.3 (Cq). MS (EI): m/z (%) 286 (M1, 12), 257 (64), 229
(88), 202 (100), 189 (68), 165 (50), 152 (30), 115 (14).
HRMS (C22H22) calcd: 286.1720, found: 286.1719.
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