Acid-catalyzed cascade ring-opening and addition reactions of arylvinylcyclopropenes with α, β-unsaturated substrates, scope and limitations

Article abstract of DOI:10.1021/jo802786r

Catalyzed by Al(III) catalyst, arylvinylcyclopropenes react with a,/3-unsaturated substrates smoothly to produce the Diels-Alder adducts in moderate to good yields through a cascade ring-opening reaction/ Diels-Alder cycloaddition. On the other hand, stro

Full text of DOI:10.1021/jo802786r

Acid-Catalyzed Cascade Ring-Opening and Addition Reactions of
Arylvinylcyclopropenes with r,ꢀ-Unsaturated Substrates,
Scope and Limitations
Zhi-Bin Zhu‡ and Min Shi*,†,‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032 China, and Laboratory for AdVanced Materials
and Institute of Fine Chemicals, East China UniVersity of Science & Technology, 130 Meilong Road,
Shanghai 200237, People’s Republic of China
mshi@mail.sioc.ac.cn
ReceiVed December 21, 2008
Catalyzed by Al(III) catalyst, arylvinylcyclopropenes react with R,ꢀ-unsaturated substrates smoothly to
produce the Diels-Alder adducts in moderate to good yields through a cascade ring-opening reaction/
Diels-Alder cycloaddition. On the other hand, strong Brønsted acid TfOH can promote the cascade
intramolecular Friedel-Crafts/1,4-addition reaction to produce indene derivatives in moderate to good
yields under mild conditions. The acidity of the catalysts plays a key role in these reactions.
Introduction
or 260-298 °C led to dimethylpenta-1,3-dienes (Scheme 1,
reaction b).5 Alternatively, if there is no methyl group or only
one methyl group at the C-3 position, the pyrolysis of cyclo-
propenes afforded alkyne products (Scheme 1, reactions c and
d).6 Furthermore, Brønsted acid (TsOH) could promote the ring-
opening reaction of cyclopropene to afford the corresponding
1,3-diene product when the ꢀ-cationic center is stabilized by
the trimethylsilyl group (Scheme 1, reaction e).7
These ring-opening products give the probability that cyclo-
propenes can act as dienes to react with other dienophiles in a
cascade reaction process with such ring-opening reaction
followed by the Diels-Alder cycloaddition, which was different
from the common roles of dienophiles that cyclopropenes acted
in most cases.8 Namely, as common dienophiles, cyclopropenes
can directly react with various dienes under mild conditions to
give the corresponding formal Diels-Alder products, six-
membered rings with up to four stereogenic centers, in a regio-
Cyclopropenes,1 as highly strained small ring species, have
been of continuing interest in the past few decades.2 One of
the most common behaviors of cyclopropenes is the ring-
opening reaction under various conditions. For example, pho-
toirradiation3 of 1,2-diphenyl-3,3-dimethylcyclopropene pro-
duced the isomeric dienes in a 3:l ratio (Scheme 1, reaction
a).4 Moreover, thermolysis of tetramethylcyclopropene at 490
* Corresponding author. Fax: 86-21-64166128.
‡ East China University of Science & Technology.
† Chinese Academy of Sciences.
(1) For a review, see: Baird, M. S. Cyclopropenes: Synthesis: By Construction
of the System. Houben-Weyl; Thieme: Stuttgart, Germany, 1997; E17d/2,
p 2695.
(2) For reviews, see: (a) Rubin, M.; Rubina, M.; Gevorgyan, V. Chem. ReV.
2007, 107, 3117. (b) Rubin, M.; Rubina, M.; Gevorgyan, V. Synthesis 2006,
1221. (c) Fox, J. M.; Yan, N. Curr. Org. Chem. 2005, 9, 719. (d) Walsh, R.
Chem. Soc. ReV. 2005, 34, 714. (e) Dolbier, W. R., Jr.; Battiste, M. A. Chem.
ReV. 2003, 103, 1071. (f) Sekiguchi, A.; Lee, V. Y. Chem. ReV. 2003, 103,
1429. (g) Chen, K.-C.; Lee, G.-A. Huaxue 2006, 64, 73. (h) Baird, M. S. Chem.
ReV. 2003, 103, 1271.
(5) Selective examples of thermolysis of cyclopropenes, see: (a) Stechl, H.-
H. Chem. Ber. 1964, 97, 2681. (b) Srinivasan, R. J. Chem. Soc., Chem. Commun.
1971, 1041.
(6) Srinivasan, R. J. Am. Chem. Soc. 1969, 91, 6250.
(7) Padwa, A.; Wannamaker, M. W.; Dyszlewski, A. D. J. Org. Chem. 1987,
52, 4760.
(3) For a review of excited state chemistry of cyclopropenes, see:Padwa, A.
Acc. Chem. Res. 1979, 12, 310.
(4) Arnold, D. R.; Pincock, J. A.; Morchat, R. J. Am. Chem. Soc. 1973, 95,
7536.
10.1021/jo802786r CCC: $40.75
Published on Web 02/23/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2481–2485 2481

Zhu and Shi
SCHEME 1. Ring-Opening Reactions of Cyclopropenes
FIGURE 1. ORTEP drawing of compound 3a.
SCHEME 2. AlCl3-Catalyzed Cascade Ring-Opening
Diels-Alder Reaction
and stereocontrolled way and in good yields.9 In this paper, we
wish to report the acid-catalyzed regioselective ring-opening
reaction of arylvinylcyclopropenes 110 followed by Diels-Alder
cycloaddition with R,ꢀ-unsaturated substrates to construct
cyclohexene skeletons, in which cyclopropenes acted as pre-
dienes rather than dienophiles to construct six-membered-ring
compounds. Moreover by changing the catalyst to a stronger
Brønsted acid, a cascade intramolecular Friedel-Crafts/1,4-
addition of 1 with R,ꢀ-unsaturated substrates took place to
produce indene derivatives under identical conditions.
TABLE 1. Ring-Opening Reaction of 1a in the Presence of
Various Lewis or BrOnsted Acids
Results and Discussion
To obtain the ring-opening products of phenylvinylcyclopro-
pene 1a, we initially attempted pyrolysis of 1a at 260 °C, but
it was found that none of the corresponding ring-opening product
4a was formed. Furthermore, by adding maleic anhydride 2a
under the same condition to trap the in situ formed 4a, we found
that complicated reaction products were obtained, presumably
due to both of the reactants and the products are being stable at
such high temperature. Then, using 0.1 equiv of AlCl3 as the
catalyst, it was found that the Diels-Alder cycloaddition product
3a, derived from the reaction of ring-opening product 4a (the
E-configuration of 4a was deduced by the retro-D-A reaction
of endo-adduct 3a) with 2a, was obtained in 80% yield along
with the rearrangement product 6a in 16% yield at 70 °C in
1,2-dichloroethane (DCE). In addition, the product 3a did not
undergo further Diels-Alder cycloaddition with another mol-
ecule of 2a, presumably due to the steric hindrance of the two
adjacent phenyl groups (Scheme 2). Compound 3a was unam-
yield (%)b
5a
entrya
cat.
AlCl3
AlCl3
CH3CO2H
HCl
ZrCl4
TsOH
TsOH
cat. Al(III)
cat. Al(III)
cat. Al(III)
cat. Al(III)
solvent
T (°C)
4a
6a
1
2
3
4
5
6
7
8
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
toluene
DCM
THF
20
70
70
70
70
20
70
70
70
20
70
49
35
56
14
39
88
25
39
10
57
40
97
92
9
10
11
17
a All reactions were carried out with 1a (0 0.2 mmol) in the presence
of the listed catalysts (10 mol %) and solvent (1.0 mL). b Isolated
yields.
(8) For examples, see: (a) Law, D. C. F.; Tobey, S. W. J. Am. Chem. Soc.
1968, 90, 2376. (b) Deem, M. L. Synthesis 1972, 675. (c) Battiste, M. A.
Tetrahedron Lett. 1964, 3795. (d) Closs, G. L. In AdVances in Alicyclic Systems;
Hart, H., Karabatsos, G. J., Eds.; Academic Press: New York, 1966; pp 53-
127. (e) Apeloig, Y.; Arad, D.; Kapon, M.; Wallerstein, M. Tetrahedron Lett.
1987, 28, 5917. (f) Battiste, M. A.; Posey, R. G. J. Fluorine Chem. 2000, 102,
285. (g) Muller, P.; Bernardinelli, G.; Rodriquez, D.; Pfyffer, J.; Schaller, J.-P.
Chimia 1987, 41, 244. (h) Muller, P.; Bernardinelli, G.; Pfyffer, J.; Rodriquez,
D.; Schaller, J.-P. HelV. Chim. Acta 1988, 71, 544. (i) Magid, R. M.; Wilson,
S. E. J. Org. Chem. 1971, 36, 1775. (j) Battiste, M. A.; Sprouse, C. T., Jr.
Tetrahedron Lett. 1970, 4661. (k) Muller, P.; Bernardinelli, G.; Pfyffer, J.;
Schaller, J.-P. HelV. Chim. Acta 1991, 74, 993. (l) Battiste, M. A.; Kapicak,
L. A.; Mathew, M.; Palenik, G. J. Chem. Commun. 1971, 1536.
biguously determined by an X-ray diffraction (Figure 1) and
its CIF data are presented in the Supporting Information.11
To determine the optimal conditions of the ring-opening
reaction of 1a, we carried out the reactions of 1a in the presence
(11) The crystal data of 3a have been deposited in CCDC with the number
679736. Empirical formula: C33H32O5; formula weight: 508.59; crystal color,
habit: colorless, prismatic; crystal dimensions: 0.457 × 0.411 × 0.347 mm; crystal
system: Monoclinic; lattice type: primitive; lattice parameters: a ) 16.4843(15)
Å, b ) 9.9238(9) Å, c ) 16.6985(16) Å, R ) 90°, ꢀ ) 106.622(2)°, γ ) 90°,
(9) Fringuelli, F.; Taticchi A. The Diels-Alder Reaction: Selected Practical
Methods; Wiley: New York, 2002; p 1.
(10) (a) Shao, L.-X.; Zhang, Y.-P.; Qi, M.-H.; Shi, M. Org. Lett. 2007, 9,
117. (b) Shi, M.; Jiang, M.; Liu, L.-P. Org. Biomol. Chem. 2007, 5, 438.
V ) 2617.5(4) Å3; space group: P2(1)/c; Z ) 4; Dcalc ) 1.291 g/cm3; F000
1080; diffractometer: Rigaku AFC7R; residuals: R ) 0.0900, Rw ) 0.2676.
)
2482 J. Org. Chem. Vol. 74, No. 6, 2009

Acid-Catalyzed Reactions of ArylVinylcyclopropenes
TABLE 2. Scope of the Cascade Ring-Opening and Diels-Alder Cycloaddition
a All reactions were carried out with 1 (0.2 mmol) and 2 (0.3 mmol) in the presence of Al-catalyst (0.02 mmol) and DCE (2.0 mL) at 70 °C for 24 h.
b Isolated yields. c 2 (2 mmol) was used.
of various Lewis and Brønsted acids. At room temperature, no
reaction occurred in the presence of AlCl3 in DCE (Table 1,
entry 1). At 70 °C, 4a was provided in 49% yield along with
the rearrangement product 1,4-diphenyl-2-(propan-2-ylidene)-
1,2-dihydronaphthalene 5a in 35% yield and naphthalene
derivative 6a in 14% (Table 1, entry 2). The structure of 5a
was further confirmed by X-ray diffraction and its CIF data are
presented in the Supporting Information.12 With acetic acid as
the catalyst at 70 °C, no reaction occurred (Table 1, entry 3).
Brønsted acid HCl did not produce 4a, affording 5a and 6a in
56% and 39% yield, respectively (Table 1, entry 4). Using ZrCl4
as the catalyst provided naphthalene derivative 6a exclusively
in 88% yield, which is very similar as that catalyzed by
BF3 ·OEt2 (Table 1, entry 5).10 Using Brønsted acid TsOH as
the catalyst afforded 4a in 10% yield along with 57% of 5a
and 25% of 6a at 20 °C (Table 1, entry 6). On the other hand,
5a and 6a were formed in 40% and 39% yield, respectively, at
70 °C without the formation of 4a, which is significantly
different from those reactions shown in Scheme 1 since substrate
1a does not have a TMS group to stabilize the cationic
intermediate13 (Table 1, entry 7). Interestingly, although we
could not obtain 4a in 80% yield when AlCl3 was used as the
catalyst (80% of 3a was formed as shown in Scheme 2), it was
found that using AlCl3 hydrolyzed Al(III) powder14 as the
catalyst [indicated as cat. Al(III) in this paper] produced 4a in
97% yield in DCE at 70 °C exclusively (Table 1, entry 8). In
toluene, 4a was formed in 92% yield under the standard
conditions (Table 1, entry 9). The examination of solvent effects
revealed that DCE is the best one for the reaction to give the
corresponding ring-opening product 4a exclusively in higher
yield (Table 1, entries 8-11).
(13) Colvin, E. W. Chem. Soc. ReV. 1978, 7, 15.
(14) We also found that the AlCl3 used in Scheme 2 was partially hydrolyzed
by water, but if using Al(OH)3 as the catalyst, no reaction occurred along with
the recovery of the starting materials 1a. Therefore, we found that Al(III) complex
[Al(OH)2Cl]n, which was prepared by partial hydrolysis of AlCl3 with water, is
the effective catalyst in this reaction. See the Supporting Information for the
details.
(12) The crystal data of 5a have been deposited in CCDC with the number
672065.
(15) The crystal data of 7a have been deposited in CCDC with the number
687327.
J. Org. Chem. Vol. 74, No. 6, 2009 2483

Zhu and Shi
TABLE 3. TfOH-Catalyzed Reactions of 1 with 2f-h
a All reactions were carried out with 1 (0.2 mmol) and 2 (0.6 mmol)
in the presence of TfOH (0.02 mmol) and DCE (2.0 mL) at 70 °C for
24 h. b Isolated yields.
With the best reaction conditions in hand, we next examined
the cascade ring-opening and Diels-Alder cycloaddition of a
variety of arylvinylcyclopropenes 1 with R,ꢀ-unsaturated sub-
strates 2 and the results of these experiments are summarized
in Table 2. The reactions of 1a with 2a, 1-phenyl-1H-pyrrole-
2,5-dione 2b, and diethyl but-2-ynedioate 2c proceeded smoothly
to give the corresponding D-A adducts 3a-c in good to
excellent yields (Table 2, entries 1-3). As for unsymmetrical
dienophiles 2d-f, regioisomeric mixtures 3 and 3′ were obtained
in good to excellent yields (Table 2, entries 4-6). By using 2c
as the dienophile to examine the reactions with other arylvi-
nylcyclopropenes 1b-f, the corresponding D-A adducts 3b-f
were obtained in good yields under the standard conditions
(Table 2, entries 7-11).
FIGURE 2. ORTEP drawing of compound 7a.
SCHEME 3. A Plausible Reaction Mechanism
During the examination of the catalytic ability of Brønsted
acids in this reaction, it was found that if the strong Brønsted
acid trifluoromethanesulfonic acid (CF3SO3H, TfOH) was used
as the catalyst, the naphthalene derivatives 7 were obtained via
the cascade intramolecular Friedel-Crafts/1,4-addition process
rather than the expected formal D-A cycloadducts or the ring-
opening products 4. For example, with methyl vinyl ketone 2f
and acrylaldehyde 2g as the substrates to react with 1a in DCE
in the presence of TfOH (10 mol%), naphthalene derivatives
7a and 7b were obtained in 70% and 15% yield, respectively
(Table 3, entries 1 and 2). Arylvinylcyclopropenes 1c and 1e
could also react with 2f to produce naphthalene derivatives 7c
and 7d in moderate to good yields and since the substitutions
on the aromatic rings are at the para position, only one product
can be produced when the intramolecular Friedel-Craft reaction
took place (Table 3, entries 3 and 4). As for cyclopent-2-enone
2h, the corresponding naphthalene derivative 7e was formed in
60% yield in the reaction with 1a (Table 3, entry 5).
sponding 1,2-dihydronaphthalene derivative 5 other than depro-
tonation,10 which reacts with protonated R,ꢀ-unsaturated ketone
or aldehyde to produce intermediate F. Isomerization of
intermediate F gives the corresponding naphthalene derivative
7 (Scheme 3).
It should be noted that it is impossible to prepare alkylvi-
nylcyclopropenes (both R1 are alkyl groups or one R1 is an alkyl
group) via the corresponding alkylvinylidenecyclopropanes by
using our previously reported procedure since the corresponding
enynes were produced exclusively (see the Supporting Informa-
tion for details).10
In conclusion, we have found an interesting cascade reaction
of ring-opening of arylvinylcyclopropenes followed by cyclo-
or 1,4-addition with a variety of R,ꢀ-unsaturated substrates
catalyzed by Brønsted acids, which affords an efficient synthetic
protocol for the preparation of functionalized cyclohexene or
indene derivatives. Further work directed at elucidation of the
detailed mechanism of this process and the application of it to
the synthesis of cyclohexene or indene containing natural
products is currently in progress.
The structure of compound 7a was unambiguously determined
by X-ray diffraction and its CIF data are presented in the
Supporting Information (Figure 2).15
A plausible mechanism for the formation of cycloadducts 3
and conjugate addition products 7 is outlined in Scheme 3.
Initially, the protonation of arylvinylcyclopropene 1 by acid
(Al(III) catalyst or TfOH) produces intermediate A or A′ (path
I or path II), which undergoes a ring-opening process to give
intermediate B or C. Intermediate C can be converted to
intermediate B via 1,2-proton transfer. Deprotonation of inter-
mediate B produces 4, and followed by a Diels-Alder cycload-
dition with 2 catalyzed by Al(III) catalyst to give D-A adduct
3. In the presence of strong Brønsted acid TfOH, intermediate
B undergoes intramolecular isomerization to afford the corre-
Experimental Section
General Procedure for the Preparation of Al(III) Catalyst
[cat. Al(III): Al(OH)2Cl]. Water (10 mL) was added dropwise into
aluminum chloride (4.0 g, 0.2 mmol) then the solution was dried
by a blast oven. This catalyst was indicated as cat. Al(III) in this
paper.
2484 J. Org. Chem. Vol. 74, No. 6, 2009

Acid-Catalyzed Reactions of ArylVinylcyclopropenes
Al-Catalyzed Ring-Opening Diels-Alder Reaction of
Arylvinylcyclopropenes 1a with Maleic Anhydride 2a. Under
an argon atmosphere, 1,1-diphenyvinylcyclopropene (64 mg, 0.2
mmol), maleic anhydride 2a (30 mg, 0.3 mmol), and cat. Al(III)
(2 mg, 0.02 mmol) were added into a Schlenk tube. The reaction
mixture was stirred at 70 °C for 24 h to give 3a in 86% yield after
column chromatography.
Compound 7a: white solid, mp 69-70 °C; IR (CH2Cl2) ν 3058,
3059, 3002, 2959, 1948, 1716, 1590, 1360, 1165, 1073, 1031, 892,
1
770, 730, 703 cm-1; H NMR (300 MHz, CDCl3, TMS) δ 1.22
(6H, s, CH3), 1.85 (2H, t, J ) 8.1 Hz, CH2), 2.04 (3H, s, CH3),
2.28 (2H, J ) 8.1 Hz, CH2), 7.12-7.54 (14H, m, Ar), 7.88 (1H, d,
J ) 8.4 Hz, Ar); 13C NMR (75 MHz, CDCl3, TMS) δ 30.0, 31.3,
37.9, 40.0, 40.1, 125.3, 125.4, 125.5, 127.2, 127.3, 127.7, 127.8,
127.9, 128.3, 129.8, 130.2, 131.2, 134.8, 137.5, 139.5, 141.0, 141.1,
141.2, 209.1; MS (EI) m/z (%) 392 (71.12) [M+], 393 (24.65), 322
(31.68), 321 (100), 307 (13.47), 306 (29.67), 305 (13.74), 291
(40.65), 43 (13.76); HRMS (EI) calcd for C29H28O (M+) requires
392.2140, found 392.2132.
TfOH-Catalyzed Reaction of Arylvinylcyclopropenes 1a
with Methyl Vinyl Ketone 2f. Under an argon atmosphere, 1,1-
diphenyvinylcyclopropene 1a (64 mg, 0.2 mmol), methyl vinyl
ketone 2f (50 µL, 0.6 mmol), and TfOH (2 µL, 0.02mmol) were
added into a Schlenk tube. The reaction mixture was stirred at 70
°C for 24 h to give 7a in 70% yield after column chromatography.
Compound 3a: white solid, mp 179-181 °C; IR (CH2Cl2) ν
3028, 2903, 2849, 1855, 1782, 1711, 1489, 1443, 1219, 1109, 999,
Acknowledgement. Financial support from the Shanghai
Municipal Committee of Science and Technology (06XD14005
and 08dj1400100-2), National Basic Research Program of China
(973)-2009CB825300, and the National Natural Science Foun-
dation of China (20872162, 20672127, 20732008, 20821002,
and 20702013) is greatly acknowledged.
1
902, 769, 698, 588 cm-1; H NMR (300 MHz, CDCl3, TMS) δ
1.84 (3H, s, CH3), 2.49 (1H, dd, J1 ) 11.4 Hz, J2 ) 19.2 Hz, CH2),
2.88 (1H, d, J ) 19.2 Hz, CH2), 3.02 (1H, dd, J1 ) 7.2 Hz, J2 )
9.9 Hz, CH), 3.24-3.31 (1H, m, CH), 3.66 (1H, d, J ) 7.2 Hz,
CH), 6.46 (1H, s, CH), 6.88-6.91 (2H, m, Ar), 7.10-7.24 (10H,
m, Ar), 7.34-7.37 (3H, m, Ar); 13C NMR (75 MHz, CDCl3, TMS)
δ 20.6, 27.1, 37.5, 43.8, 45.7, 127.0, 127.6, 127.8, 127.9, 128.0,
128.1, 128.3, 128.6, 128.7, 129.5, 129.9, 131.5, 136.5, 140.4, 142.3,
143.8, 171.1, 173.7; MS (EI) m/z (%) 420 (43.73) [M+], 378
(31.55), 377 (100), 331 (26.09), 253 (28.80), 231 (69.29), 215
(26.46), 167 (37.70), 91 (38.02); HRMS (EI) calcd for C29H24O3
(M+) requires 420.1725, found 420.1723.
Supporting Information Available: Spectroscopic data of
the compounds shown in Tables 1-3 and detailed descriptions
of experimental procedures. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO802786R
J. Org. Chem. Vol. 74, No. 6, 2009 2485