Novel ene trimerization of 1-phenylcyclopropene

Article abstract of DOI:10.1021/jo048889f

1-Phenylcyclopropene (1) was synthesized by treatment of 1,1,2-tribromo-2-phenylcyclopropane (2) with 2.5 equiv of methyllithium followed by protonation. Compound 1 underwent ene dimerization to form ene dimer 5 followed by ene reaction with monomer 1 (enophile) to give an ene trimer 6. Both of these two ene reactions derived endo transition states. In the meantime, the [2+2] adduct, trans-1,2-diphenylbicyclo[3.1.0.0^2,4]hexane (7), was also formed. When the adduct 7 was heated at THF refluxing temperature, 1,2-diphenylcyclohexa-1,4-diene (8) was obtained. Compound 8 was treated with DDQ to yield o-diphenylbenzene.

Full text of DOI:10.1021/jo048889f

SCHEME 1
Novel Ene Trimerization of
1-Phenylcyclopropene
Gon-Ann Lee* and Chih-Yi Chang
Department of Chemistry, Fu Jen Catholic University,
Hsinchuang, Taipei 24205, Taiwan, Republic of China
chem1010@mails.fju.edu.tw
Received July 1, 2004
Abstract: 1-Phenylcyclopropene (1) was synthesized by
treatment of 1,1,2-tribromo-2-phenylcyclopropane (2) with
2.5 equiv of methyllithium followed by protonation. Com-
pound 1 underwent ene dimerization to form ene dimer 5
followed by ene reaction with monomer 1 (enophile) to give
an ene trimer 6. Both of these two ene reactions derived endo
transition states. In the meantime, the [2+2] adduct, trans-
1,2-diphenylbicyclo[3.1.0.02,4]hexane (7), was also formed.
When the adduct 7 was heated at THF refluxing tempera-
ture, 1,2-diphenylcyclohexa-1,4-diene (8) was obtained. Com-
pound 8 was treated with DDQ to yield o-diphenylbenzene.
propenes but only one of them contained 3-hydrogen.
Therefore the regio- and stereochemistry of this crossed
ene reaction are less complicated than that of both
cyclopropenes containing 3-hydrogen. Okamoto and co-
worker reported that 1,2-diarylcyclopropenes did react
with strong enophiles such as tetracyanoethylene, diben-
zoylacetylene, and dimethyl acetylenedicarboxylate but
did not show any reactivity toward hydrocabonenes (e.g.,
3-phenylpropene) or enophiles (e.g., diphenylacetylene).5b
There was only one cyclopropene, bicyclo[5.1.0]hept-1(8)-
ene, reported that underwent ene trimerization, another
type of crossed ene reaction of monomer with ene dimer,
to give an ene trimer.3e This ene trimer was only
determined by 1H NMR and mass spectrometry in crude
mixture and was not isolated or trapped to prove its
existence and the stereochemistry and regiochemistry of
these ene reactions were still unknown. Although 1-phen-
ylcyclopropene (1) has been synthesized,6 the chemistry
of 1 has not been investigated yet. In this paper we
describe an easier synthetic route and the characteristic
facile ene trimerization of 1-phenylcyclopropene (1).
Compound 1 was prepared and trapped in solution by
the method shown in Scheme 1. 1,1,2-Tribromo-2-phen-
ylcyclopropane (2),4b,9 the immediate precursor via de-
halogenation, halo-lithium exchanged reaction, and pro-
tonation to compound 1, was generated by dibromocar-
bene addition to R-bromostyrene.4b When cyclopropane
Cyclopropene is known to dimerize and polymerize at
room temperature via ene reactions to release the olefinic
strain.1 Substituted cyclopropenes are generally more
stable and can dimerize via ene reactions to give 3-cy-
clopropylcyclopropenes,2 [2+2] cyclizations to form tricycle-
[3.1.0.02,4]hexanes,3 and coupling reactions to yield 1,3,5-
hexatriene3c-f,4 at higher temperature. Due to their high
strain energy, cyclopropenes containing 3-hydrogen usu-
ally undergo ene dimerizations. Asymmetric cyclopro-
penes usually undergo ene reactions to form several
regio- and stereodimers.3e,4b,5 In the literature, there are
only a few cyclopropenes which undergo crossed ene
reactions faster than ene dimerizations. Baird and co-
worker reported that 3,3-dimethylcyclopropenecarboxylic
acid and 2-tert-butylcyclopropenecarboxylic acid only
underwent crossed ene reactions via an exo approach of
the dimethylcyclopropene and the ene dimer of 2-tert-
butylcyclopropenecarboxylic acid was not obtained.5c This
crossed ene reaction resulted from two different cyclo-
(1) (a) Schlatter, M. J. J. Am. Chem. Soc. 1941, 63, 1733. (b) Wiberg,
K. B.; Bartley, W. J. J. Am. Chem. Soc. 1960, 82, 6375. (c) Dowd, D.;
Gold, A. Tetrahedron Lett. 1969, 85.
(2) (a) Breslow, R.; Dowd, P. J. Am. Chem. Soc. 1963, 85, 2729. (b)
Garratt, P. J.; Tsotinis, A. J. Org. Chem. 1990, 55, 84.
(3) (a) DeBoer, C. D.; Wadsworth, D. H.; Perkins, W. C. J. Am. Chem.
Soc. 1973, 95, 861. (b) Pincock, J. A.; Moutsokapas, A. A. Can. J. Chem.
1977, 55, 979. (c) Padwa, A.; Kennedy, G. D.; Newkome, G. R.;
Fronczek, F. R. J. Am. Chem. Soc. 1983, 105, 137. (d) Wiberg, K. B.;
Artis, D. R.; Bonneville, G. J. Am. Chem. Soc. 1991, 113, 7969. (e)
Billups, W. E.; Lee, G.-A.; Arney, B. E., Jr.; Whitmire, K. H. J. Am.
Chem. Soc. 1991, 113, 7980. (f) Billups, W. E.; Luo, W.; Lee, G.-A.;
Chee, J.; Arney, B. E., Jr.; Wiberg, K. B.; Artis, D. R. J. Org. Chem.
1996, 61, 764.
(4) (a) Baird, M. S. Chem. Rev. 2003, 103, 1271. (b) Lee, G.-A.;
Chang, C.-Y. Tetrahedron Lett. 1998, 39, 3013. (c) Baird, M. S.;
Hussain, H. H. Tetrahedron 1989, 45, 6221.
(5) (a) Deng, Q.; Thomas, B. E., IV; Houk, K. N.; Dowd, P. J. Am.
Chem. Soc. 1997, 119, 6902. (b) Komatsu, K.; Niwa, T.; Akari, H.;
Okamoto, K. J. Chem. Res., Miniprint 1985, 8, 2847. (c) Baird, M. S.;
Hussein, H. H.; Clegg, W. J. Chem. Res., Miniprint 1988, 4, 1101. (d)
Lee, G.-A.; Shiau, C.-S.; Chen, C.-S.; Chen, J. J. Org. Chem. 1995, 60,
3565. (e) Lee, G.-A.; Chen, C.-S. Tetrahedron Lett. 1997, 38, 8717.
2
4b,9 was treated with 2.5 equiv of methyllithium followed
by cyclopentadiene at -40 °C, two compounds were
isolated (73 and 25%) (Scheme 1). The major product 3
was formed from cylopropene 1 with cyclopentadiene. The
structure of the minor product 4 was shown by X-ray
crystallography (Figure 1) and it was formed from an ene
dimer 5 and cyclopentadiene. The ene dimer 5 was
formed via an endo transition state. Cyclopropene 1 is
very active and one-quarter of 1 undergoes ene reaction
before reacting with cyclopentadiene.
(6) Stoll, A. T.; Negishi, E. Tetrahedron Lett. 1985, 26, 5671.
(7) Carbonaro, A.; Greco, A.; Dall’asta, G. J. Org. Chem. 1968, 33,
3948.
(8) 1H NMR: Griffiths, C.; Leadbeater, N. E. Tetrahedron Lett. 2000,
41, 2487. 13C NMR: Freeman, P. K.; Pugh, J. K. J. Org. Chem. 1999,
64, 3947.
(9) Sydnes, L. K.; Bakstad, E. Acta Chim. Scand. 1996, 50, 446.
10.1021/jo048889f CCC: $27.50 © 2004 American Chemical Society
Published on Web 11/06/2004
J. Org. Chem. 2004, 69, 8949-8951
8949

FIGURE 3. The structure of compound 9 (hydrogen atoms
omitted).
SCHEME 2
FIGURE 1. The structure of compound 4 (hydrogen atoms
omitted).
and 226.4 kcal/mol, respectively. The heat of ene dimer-
ization is - 45.7 kcal/mol, and the heat of the reaction of
1 and 5 to give 6 is -48.1 kcal/mol, supportive of the
favored ene trimerization over the ene dimerization. The
heat of the reaction of 6 and 1 to yield the endo tetramer
is -41.4 kcal/mol, indicating why there is no observation
of ene tetramerization.
FIGURE 2. The structure of compound 7 (hydrogen atoms
omitted).
To generate high-yield ene dimer 5, compound 1 was
synthesized and kept at -30 °C for 48 h followed at 0 °C
for 24 h and two adducts 6 and 7 were isolated in the
yields of 88% and 8%, respectively. The 13C NMR
spectrum of 6 showed 21 signals (triple of monomer’s
signals) including 14 alkene carbons as expected for an
ene trimer 6. The structure of 7, trans-1,2-diphenylbicyclo-
[3.1.0.02,4]hexane, was shown by X-ray crystallography
(Figure 2) and it was formed via a head-to-head [2+2]
dimerization reaction. When the adduct 7 was heated at
THF refluxing temperature, 1,2-diphenylcyclohexa-1,4-
diene (8) was obtained.7 Compound 8 was treated with
DDQ to yield o-diphenylbenzene.8
∆H(Hf of dimer - Hf of monomer × 2) )
-45.7 (kcal/mol) (1)
∆H(Hf of trimer - Hf of monomer - Hf of dimer) )
-48.1 (kcal/mol) (2)
∆H(Hf of tetramer - Hf of monomer -
Hf of trimer) ) -41.4 (kcal/mol) (3)
It is interesting to note that, despite the ready ene
dimerization of 1, there was no evidence of products other
than 6 and 7. Because the ene trimer 6 was unstable in
the presence of water and oxygen, compound 6 was
trapped with cyclopentadiene to form a stable adduct 9
to study the regio- and stereochemistry of 6 (Scheme 2).
This is the first confirmed ene trimerization. The struc-
ture of adduct 9 was shown by single-crystal X-ray
analysis (Figure 3). Compound 6 was generated by the
endo transition state from 1 (enophile) and 5 (hydrogen
donator). We also attempted to prepare the ene tetramer
of 1 by treatment of 6 with 1 but only compound 6 was
obtained.
In summary, we discovered an easier route to synthe-
size 1-phenylcyclopropene (1). Compound 1 underwent
ene dimerization to from ene dimer 5 followed by ene
reaction with monomer 1 (enophile) to give an ene trimer
6. Both of these ene reactions derived endo transition
states. In the meantime, the [2+2] adduct 7 was also
formed and this reaction provides a feasible route to
o-diarylbenzene.
Experimental Section
General. Melting points are determined and uncorrected.
Proton and carcon-13 NMR spectra were measured in CDCl3
with CHCl3 as the internal standard. Chemical shifts (δ) are
expressed in ppm downfield from tetramethylsilane and coupling
The PM3 theoretical calculations of heats of formation
of 1, 5, 6, and the endo tetramer are 90.4, 135.1, 177.4,
8950 J. Org. Chem., Vol. 69, No. 25, 2004

constants are expressed in hertz. X-ray data were recorded on
a Siemens P4 diffractometer for compounds 4, 7, and 9. Calcula-
tions were performed with the HyperChem Molecular Modeling
System for Windows, Version 6.03, geometry optimization,
semiempirical, PM3. Silica gel (70-230 mesh) for column
chromatography and silica gel (230 mesh) for flash chromatog-
raphy were from E. Merck. Solvents are reagent grade.
1,1,2-Tribromo-2-phenylcyclopropane (2). R-Bromo-
styrene (14.2 g, 78 mmol), 21 mL of bromoform, 21 mL of 50%
of sodium hydroxide, and 0.1 g of n-tetrabutylammonium
bromide were placed into a 100-mL flask. The mixture was
stirred for 20 h at 80 °C, and then 25 mL of methylene chloride
and 20 mL of water were added. The water layer was extracted
with methylene chloride (3 × 25 mL). The combined organic
solution was washed with water and brine and dried over
anhydrous sodium sulfate, filtered, concentrated, and chromato-
graphed (hexanes) to give white solid 2 (21.04 g, 76%, mp 83.5-
84.5 °C).
2.30 (m, 2H), 2.03 (d, 1H, J ) 3.9 Hz), 1.80-1.74 (m, 1H), 1.67-
1.53 (m, 2H), 1.31-1.21 (m, 1H), 1.02-0.92 (m, 2H); 13C NMR
(CDCl3) δ 143.8 (C), 143.3 (C), 130.1 (C), 128.7 (CH), 128.6 (CH),
128.5 (CH), 128.3 (CH), 127.5 (CH), 126.1 (CH), 126.0 (CH), 125.9
(CH), 125.2 (CH), 120.7 (C), 111.4 (C), 27.6 (CH), 26.3 (CH), 22.5
(CH), 21.8 (CH), 20.5 (CH), 16.3 (CH2), 15.7 (CH2). Compound
7: mp 43.0-43.5 °C; IR (neat, cm-1) 3054, 3026, 2972, 1600,
1497, 1446, 1290, 1230, 1118, 1024, 819, 784, 747, 697; 1H NMR
(CDCl3) δ 7.14-7.32 (m, 10H), 2.02 (dd, 2H, J ) 2.5, 3.7 Hz),
1.82-1.85 (m, 4H); 13C NMR (CDCl3) δ 140.4 (C), 128.3 (CH),
125.5 (CH), 125.1 (CH), 32.4 (C), 31.3 (CH2), 29.3 (CH); MS (EI)
m/z (%) 232 (M+, 100), 215 (74), 141 (66), 91 (89); HRMS calcd
for C18H16 m/z 232.1252, found 232.1253. Anal. Calcd for
C18H16: C 93.06, H 6.94. Found: C 92.99, H 7.04.
1,2-Diphenylcyclohexa-1,4-diene (8).7 A solution of 7 (0.46
g, 2.0 mmol) in THF (20 mL) was stirred and heated at THF
refluxing temperature for 8 h. The reaction mixture was
concentrated and the residue was purified by chromatography
(hexanes) to give white solid 8 (0.42 g, 91%). Compound 8: 1H
NMR (CDCl3) δ 7.15-7.05 (m, 10H), 5.86 (t, 2H, J ) 2.7 Hz),
3.13 (d, 4H, J ) 1.4 Hz).
Oxidation of Compound 8. A solution of 8 (0.11 g, 0.48
mmol) in glacial acetic acid (60 mL) containing 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) (0.13 g, 0.57 mmol) was stirred
for 0.5 h at room temperature. About 30 mL of hexanes was
added, and the mixture was poured into a 250-mL beaker with
100 mL of iced water. The organic layer was separated and
washed with water and brine, then dried over anhydrous
magnesium sulfate, filtered, concentrated, and chromatographed
(hexanes) to give o-diphenylbenzene (0.095 g, 86%).8 o-Di-
phenylbenzene: 1H NMR (CDCl3) δ 7.47-7.42 (m, 4H), 7.27-
7.15 (m, 10H); 13C NMR (CDCl3) δ 141.6 (C), 140.7 (C), 130.7
(CH), 130.0 (CH), 127.9 (CH), 127.5 (CH), 126.5 (CH).
Trapping 1-Phenylcyclopropene (1) with Cyclopenta-
diene. Methyllithium (1.5 M in ether, 23.5 mL, 35.0 mmol) was
added dropwise from a syringe to a stirred solution of 1,1,2-
tribromo-2-phenylcyclopropane (2) (5.0 g, 14.0 mmol) in 30.0 mL
of dry ether at -78 °C. The mixture was stirred at -40 °C for 2
h, then cyclopentadiene (11.5 mL, 0.14 mol) was added and the
mixture was allowed to warm to room temperature and stirred
for 12 h. About 20 mL of ether was added, then the mixture
was pour into a 250-mL beaker with 100 g of crushed ice. The
organic layer was separated and washed with water and brine,
dried over anhydrous magnesium sulfate, filtered, and then
concentrated and chromatographed (hexanes) to give colorless
oil 3 (1.86 g, 73%) and white solid 4 (0.52 g, 25%). Compound 3:
IR (neat, cm-1) 3058, 2971, 2863, 1600, 1497, 1446, 1329, 1245,
1026, 852, 792, 754, 727, 696; 1H NMR (CDCl3) δ 7.35-7.15 (m,
5H), 6.09-6.06 (m, 1H), 5.90 (dd, 1H, J ) 3.2, 5.2 Hz), 3.08-
3.06 (m, 1H), 3.04-3.02 (m, 1H), 2.12 (dt, 1H, J ) 6.9, 1.7 Hz),
1.79-1.75 (m, 2H), 1.12-1.10 (m, 2H); 13C NMR (CDCl3) δ 144.6
(C), 133.2 (CH), 132.6 (CH), 128.3 (CH), 127.4 (CH), 125.4 (CH),
62.1 (CH2), 48.4 (CH), 43.9 (CH), 28.8 (C), 26.2 (CH2), 22.6 (CH);
MS (EI) m/z (%) 182 (M+, 53), 167 (100), 115 (39), 91 (36); HRMS
calcd for C14H14 m/z 182.1096, found 182.1097. Anal. Calcd for
C14H14: C 92.26, H 7.74. Found: C 92.54, H 7.68. Compound 4:
mp 38.0-39.0 °C; IR (neat, cm-1) 3052, 2979, 2949, 2923, 2856,
1600, 1495, 1444, 1324, 1257, 1146, 875, 830, 754, 736, 698; 1H
NMR (CDCl3) δ 7.41-7.04 (m, 8H), 6.73-6.71 (m, 2H), 6.09-
6.06 (m, 1H), 5.98-5.95 (m, 1H), 3.09 (s, 1H), 2.98 (s, 1H), 2.07
(d, 1H, J ) 6.9 Hz), 1.82-1.79 (m, 1H), 1.72-1.65 (m, 2H), 1.01
(dd, 1H, J ) 2.7, 7.1 Hz), 0.84-0.77 (m, 1H), 0.72-0.65 (m, 1H),
0.54-0.47 (m, 1H); 13C NMR (CDCl3) δ 143.2 (C), 141.8 (C), 132.9
(CH), 132.4 (CH), 130.4 (CH), 128.0 (CH), 127.9 (CH), 126.2 (CH),
125.9 (CH), 125.1 (CH), 60.6 (CH2), 51.8 (CH), 43.8 (CH), 39.4
(CH), 34.9 (C), 23.4 (CH), 23.3 (CH), 22.1 (CH), 15.8 (CH2); MS
(EI) m/z (%) 298 (M+, 3.5), 232 (38), 207 (47), 165 (49), 91 (100);
HRMS calcd for C23H22 m/z 298.1722, found 298.1723. Anal.
Calcd for C23H22: C 92.57, H 7.43. Found: C 92.57, H 7.45.
Ene Trimerization and [2+2] Cyclization of 1-Phenyl-
cyclopropene (1). To a stirred solution of compound 2 (15.0 g,
42.0 mmol) in 80 mL of dry ether at - 78 °C was added
methyllithium (1.5 M in ether, 70.5 mL, 0.105 mol) dropwise
from a syringe. The mixture was stirred at -40 °C for 2 h, then
ammonium chloride (5.6 g, 0.105 mol) was added. Ether was
removed under reduced pressure and the residue was kept at
-30 °C for 48 h followed at 0 °C for 24 h, then allowed to warm
to room temperature. Hexanes (100 mL) was added, and the
mixture was filtrated, concentrated, and chromatographed
(hexanes) to give white solid 6 (4.29 g, 88%) and 7 (0.39 g, 8%).
Compound 6: 1H NMR (CDCl3) δ 7.54-7.07 (m, 15H), 2.43-
Diels-Alder Reaction of Ene Trimer 6 and Cyclopenta-
diene. Compound 6 (4.0 g, 11.0 mmol) was generated as
described above and dissolved in 40 mL of hexanes at room
temperature. After cyclopentadiene (9.0 mL, 0.11 mol) was added
the mixture was stirred for 12 h, concentrated, and chromato-
graphed (hexanes) to give white solid 9 (4.46 g, 98%). Compound
9: mp 107.0-108.0 °C; IR (neat, cm-1) 3054, 3021, 2981, 2965,
2936, 2866, 1600, 1496, 1461, 1449, 1442, 1326, 1245, 1227,
1102, 1085, 1028, 910, 876, 857, 773, 747, 695; 1H NMR (CDCl3)
δ 7.42-7.02 (m, 13H), 6.84-6.81 (m, 2H), 6.05 (dd, 1H, J ) 3.3,
5.0 Hz), 5.98-5.95 (m, 1H), 2.75 (d, 1H, J ) 1.1 Hz), 2.50 (s,
1H), 2.21 (d, 1H, J ) 7.0 Hz), 2.02-1.95 (m, 1H), 1.84-1.78 (m,
1H), 1.61 (d, 1H, J ) 7.0 Hz), 1.30-1.24 (m, 1H), 1.18-1.07 (m,
2H), 0.82-0.74 (m, 2H), 0.59-0.53 (m, 1H), 0.46-0.38 (m, 1H);
13C NMR (CDCl3) δ 143.4 (C), 143.1 (C), 140.7 (C), 133.9 (CH),
133.2 (CH), 131.3 (CH), 128.2 (CH), 128.1 (CH), 128.0 (CH), 126.2
(CH), 126.1 (CH), 125.9 (CH), 125.3 (CH), 125.2 (CH), 59.2 (CH2),
53.5 (CH), 44.2 (CH), 41.9 (CH), 35.8 (C), 31.2 (C), 24.9 (CH),
22.4 (CH), 22.3 (CH), 21.3 (CH), 16.3 (CH2), 11.9 (CH2); MS
(FAB) m/z (%) 414 (M+, 9), 310 (39), 165 (19), 115 (17); HRMS
calcd for C32H30 m/z 414.2348, found 414.2358. Anal. Calcd for
C32H30: C 92.71, H 7.29. Found: C 92.94, H 7.05.
Acknowledgment. Financial support from the Na-
tional Science Council of the Republic of China (NSC
92-2113-M-030-004) is gratefully acknowledged.
Supporting Information Available: Crystal structures
for 4, 7, and 9, and 1H and 13C NMR spectra for compounds 2,
3, 4, 6, 7, and 9. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO048889F
J. Org. Chem, Vol. 69, No. 25, 2004 8951