Carbon-carbon double-bond isomerization and diels-alder reaction of dimethyl 5-methylene-4-isopropylidene-2-cycloheptene-1,1-dicarboxylate with dienophiles

Article abstract of DOI:10.1055/s-0029-1218574

Tricyclic compounds were obtained as a single diastereomer via carbon-carbon double-bond isomerization-Diels-Alder reaction of dimethyl 5-methylene-4-isopropylidene-2-cycloheptene-1,1-dicarboxylate with dienophiles under the catalysis of [RhCl(cod)₂]₂/dppe/AgOTf. Further experiments provided the proof of isomerization of carbon-carbon double bond. Meanwhile a sequential double Diels-Alder reaction took place without carbon-carbon double-bond isomerization when 4-phenyl-4H-1,2,4-triazole-3,5-dione used as a dienophile.

Full text of DOI:10.1055/s-0029-1218574

LETTER
227
Carbon–Carbon Double-Bond Isomerization and Diels–Alder Reaction of
Dimethyl 5-Methylene-4-isopropylidene-2-cycloheptene-1,1-dicarboxylate
with Dienophiles
S
ynthesisof
T
i
ricyclic
n
Compoundsg Lu,a Jinqiang Kuang,b Shengming Ma*a,b
a
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
345 Linglin Lu, Shanghai 200032, P. R. of China
Fax +86(21)64167510; E-mail: masm@mail.sioc.ac.cn
Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University,
3663 North Zhongshan Road, Shanghai 200062, P. R. of China
b
Received 8 October 2009
R
Abstract: Tricyclic compounds were obtained as a single diastere-
omer via carbon–carbon double-bond isomerization–Diels–Alder
reaction of dimethyl 5-methylene-4-isopropylidene-2-cyclohep-
tene-1,1-dicarboxylate with dienophiles under the catalysis of
[RhCl(cod)2]2/dppe/AgOTf. Further experiments provided the
proof of isomerization of carbon–carbon double bond. Meanwhile a
sequential double Diels–Alder reaction took place without carbon–
carbon double-bond isomerization when 4-phenyl-4H-1,2,4-triaz-
ole-3,5-dione used as a dienophile.
R
2 mol% [RhCl(CO)2]2
or 2.5 mol% [RhCl(COD)]2
5 mol% dppp
R
/
R
X
X
48–78%
1
2
X = CH2(CO2Me)2, NTs, O
R = Me, Et, -(CH2)5-
Equation 1
Key words: Diels–Alder reactions, isomerizations, rhodium,
stereoselectivity, carbocycles
Et
N
O
O
MeO2C
MeO2C
H
The Diels–Alder reaction is a powerful tool for construc-
tion of complicated six-membered derivatives with good
to excellent selectivity.1 After the first report of rhodium-
catalyzed Diels–Alder reaction by Livinghouse and co-
workers,2 the chemistry of this catalytic reaction has been
greatly explored.3 Recently, the catalytic enatioselective
reactions have also been independently achieved by
Mikami’s group4 and Hayashi’s group5 using chiral rhod-
ium catalysts.
H
MeO2C
MeO2C
2 mol% [RhCl(COD)]2
2a
+
5–7 mol% dppe
H
10 mol% AgOTf
toluene
O
4a
reflux, 12 h, 97%
80 °C, 42 h, 89%
NEt
O
O
2 equiv
MeO2C
MeO2C
MeO2C
MeO2C
NEt
Recently, we have observed that the cyclometallation of
9,9-disubstituted 1,2,7,8-tetraenes under the catalysis of
[RhCl(CO)2]2 (2 mol%) or [RhCl(cod)]2 (2.5 mol%)/dppp
(5 mol%) afforded the seven-membered cross-conjugated
trienes 2 (Equation 1).6 We reasoned that the Diels–Alder
reaction of the diene unit of the cross-conjugated triene 2
with dienophile would afford complex polycyclic com-
pounds efficiently, if the issue of selectivity can be ad-
dressed. Interestingly, when 2a was treated with N-ethyl
maleimide under the catalysis of [RhCl(cod)]2/dppe/AgO-
Tf, instead of the normal [4+2] product 3a,7 tricyclic prod-
uct 4a was isolated as a single diastereomer in 97% yield,
probably via in situ generated triene 5a (Scheme 1).8 The
structure of this product was unambiguously established
by X-ray diffraction studies (Figure 1).9 The reaction was
much slower at 80 °C; however, a 89% yield could also be
achieved for 4a after 42 hours.
O
3a
5a
Scheme 1
SYNLETT 2010, No. 2, pp 0227–0230
Advanced online publication: 11.12.2009
x
x.
x
x.
2
0
1
0
Figure 1 ORTEP representation of 4a
DOI: 10.1055/s-0029-1218574; Art ID: W16409ST
© Georg Thieme Verlag Stuttgart · New York

228
P. Lu et al.
LETTER
When N-phenyl maleimide or p-iodophenyl maleimide
was treated with 2a under the same conditions, the corre-
sponding tricyclic products 4b or 4c could be isolated as a
single diastereomer in 86% yield (Scheme 2). The tricy-
clic product 4d was also formed in 66% yield as the only
diastereomer when maleic anhydride was used as the di-
enophile.
MeO2C
MeO2C
3 mol% [RhCl(cod)]2
5 mol% dppe
5a (62%)
+
10 mol% AgOTf
toluene, reflux
17 h
MeO2C
MeO2C
MeO2C
MeO2C
5a' (4%)
MeO2C
X
O
N
MeO2C
2a
O
H
2–3 mol% [RhCl(cod)]2
5 mol% dppe
2a
+
O
1 equiv AlCl3
MeO2C
MeO2C
H
10 mol% AgOTf
toluene, reflux
CH2Cl2, r.t.
18 h
MeO2C
MeO2C
H
5a' (54%)
X
4
Scheme 3
4b X = NPh, 12 h, 86%
O
4c X = N-(4-IC6H4), 12 h, 86%
4d X = O, 46 h, 66%
O
PhN
Scheme 2
O
N
O
N
toluene, r.t.
18 h
N
N
MeO2C
MeO2C
When a less active dienophile, for example, 1,4-diace-
toxy-2-butyne, was used instead of the expected tricyclic
compound, we isolated the carbon–carbon double-bond
migration product 5a in 53% yield, together with another
carbon–carbon double-bond isomer 5a¢ in ca. 40% yield,
+
NPh
MeO2C
MeO2C
O
5a
6
4e (95%)
2 equiv
which was contaminated with unidentified byproducts Scheme 4
(Equation 2). This reaction clearly indicated that the cy-
cloaddition reaction shown in Schemes 1 and 2 took place
after the formation of the carbon–carbon double-bond mi-
gration product 5a.
MeO2C
MeO2C
MeO2C
MeO2C
2.4 mol% [RhCl(COD)]2
5a (53%)
2a
+
4 mol% dppe
+
8 mol% AgOTf
toluene, reflux
24 h
AcO
OAc
MeO2C
MeO2C
1.6 equiv
5a' (~40%)
Equation 2
Figure 2 ORTEP representation of 4e
Further study led to the observation that in the absence of
the dienophile the reaction of 2a – under the same condi-
tions – afforded the carbon–carbon double-bond isomer-
ization product 5a in the yield of 62% highly selectively,
together with another carbon–carbon double-bond isomer
5a¢ in only 4% yield. The product 5a¢ was also formed ex-
clusively in the presence of Lewis acid AlCl3 in CH2Cl2
(Scheme 3).
4e was also unambiguously confirmed by the X-ray dif-
fraction studies (Figure 2).10
When this active dienophile 6 was treated with 2a under
the catalysis of [RhCl(cod)]2/dppe/AgOTf at room tem-
perature, surprisingly the polycyclic product 7 was isolat-
ed as a single diastereomer in 23% yield (Scheme 5). The
structure of 7 was unambiguously confirmed by the X-ray
diffraction studies (Figure 3).11 Obviously, the normal
Diels–Alder tricyclic product 8 was formed firstly, fol-
lowed by the further reaction with 4-phenyl-4H-1,2,4-tri-
azole-3,5-dione. Furthermore, in the absence of this
Treatment of triene 5a with 4-phenyl-4H-1,2,4-triazole-
3,5-dione (6) could also smoothly afford the tricyclic
compound 4e in 95% yield (Scheme 4). The structure of
Synlett 2010, No. 2, 227–230 © Thieme Stuttgart · New York

LETTER
Synthesis of Tricyclic Compounds
229
MeO2C
MeO2C
MeO2C
O
2a
+
toluene, r.t.
N
N
MeO2C
O
NPh
N
N
O
O
O
PhN
N
O
MeO2C
MeO2C
NPh
N
N
N
NPh
2 equiv 6
O
3 mol% [RhCl(cod)]2
5 mol% dppe
O
8
6
10 mol% AgOTf
22.5 h, 23%
4 equiv 6
22 h, 94%
Scheme 5
Acknowledgment
Financial supports from National Natural Science Foundation of
China (20732005) and Major State Basic Research Development
Program (2009CB825300) are greatly appreciated. We also thank
Mr. Jingbo Zhao in our research group for reproducing the prepara-
tions of 4d in Scheme 2, 5a¢ in Scheme 3, and 7 in Scheme 5.
References and Notes
(1) (a) Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.
Comprehensive Asymmetric Catalysis, Vol. 1-3; Springer:
Berlin, 1999. (b) Yamamoto, H. Lewis Acids in Organic
Synthesis, Vol. 1-2; Wiley-VCH: New York, 2000.
(c) Kobayashi, S.; Jørgensen, K. A. Cycloaddition Reaction
in Organic Synthesis; Wiley-VCH: New York, 2002.
(d) Jørgensen, K. A. Angew. Chem. Int. Ed. 2000, 39, 3558.
(2) Jolly, R. S.; Luedtke, G.; Sheehan, D.; Livinghouse, T.
J. Am. Chem. Soc. 1990, 112, 4965.
(3) (a) Gilbertson, S. T.; Hoge, G. S.; Genov, D. G. J. Org.
Chem. 1998, 63, 10077. (b) Heath, H.; Wolfe, B.;
Livinghouse, T.; Bae, S. K. Synthesis 2001, 2341.
(c) O’Mahony, D. J. R.; Belanger, D. B.; Livinghouse, T.
Synlett 1998, 443.
Figure 3 ORTEP representation of 7⋅2CH2Cl2
catalyst, the reaction also took place to afford 7 in 94%
yield with 4 equivalents of dienophile 6.
(4) Aikawa, K.; Akutagawa, S.; Mikami, K. J. Am. Chem. Soc.
2006, 128, 12648.
(5) Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew.
Chem. Int. Ed. 2007, 46, 7277.
(6) Lu, P.; Ma, S. Org. Lett. 2007, 9, 2095.
In conclusion, we observed here some interesting cy-
cloaddition reactions of dimethyl 5-methylene-4-isopro-
pylidene-2-cycloheptene-1,1-dicarboxylate with different
dienophiles: with maleimide or maleic anhydride, the car-
bon–carbon double-bond isomerization took place under
the catalysis of cationic rhodium catalyst first, followed
by Diels–Alder reaction, providing an efficient strategy to
the construction of tricyclic compounds with high stereo-
selectivity. On the other hand, the polycyclic product 7
could also be obtained via a sequential double Diels–
Alder reaction when 4-phenyl-4H-1,2,4-triazole-3,5-di-
one (6) was used. In this reaction, the carbon–carbon dou-
ble-bond isomerization was not observed. Further studies
in this area are being pursued in this laboratory.
(7) Wang, B.; Cao, P.; Zhang, X. Tetrahedron Lett. 2000, 41,
8041.
(8) (a) Tani, K. Pure Appl. Chem. 1985, 57, 1845; and
references cited therein. (b) Akutagawa, S. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H., Eds.; Springer: New York, 1999,
Chap. 23. (c) Fu, G. C. In Modern Rhodium-Catalyzed
Organic Reactions; Evans, P. A., Ed.; Wiley-VCH:
Weinheim, 2002, Chap. 2.
(9) Crystal Data for Compound 4a
C21H27NO6, MW = 389.44, monoclinic, Pc, final R indices
[I > 2s(I)], R1 = 0.0549, wR2 = 0.1248, R indices (all data):
R1 = 0.0633, wR2 = 0.1299, a = 13.7051 (13) Å,
b = 11.8187 (11) Å, c = 12.9999 (12) Å, b = 103.869 (2)°,
V = 2044.3 (3) Å3, T = 293 (2) K, Z = 4, reflections
collected/unique: 11758/4448 (Rint = 0.1361), number of
observations [>2s(I)] 3626, parameters, 531. Supplementary
crystallographic data have been deposited at the Cambridge
Crystallographic Data Centre: CCDC 635123.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Synlett 2010, No. 2, 227–230 © Thieme Stuttgart · New York

230
P. Lu et al.
LETTER
(10) Crystal Data for 4e
(11) Crystal Data for 7
C23H25N3O6, MW = 439.46, triclinic, P-1, final R indices
[I > 2s(I)], R1 = 0.0394, wR2 = 0.1111, R indices (all data):
R1 = 0.0498, wR2 = 0.1212, a = 8.4388 (4) Å, b = 8.5666
(4) Å, c = 16.3077 (7) Å, a = 99.1060 (10)°, b = 100.0250
(10)°, g = 105.3230 (10)°, V = 1093.44 (9) Å3, T = 296 (2)
K, Z = 2. Reflections collected/unique: 12810/ 3839
(Rint = 0.0204), number of observations [>2s(I)] 3118,
parameters, 289. Supplementary crystallographic data have
been deposited at the Cambridge Crystallographic Data
Centre: CCDC 750106.
C33H34Cl4N6O8 (M + 2CH2Cl2), MW = 784.46, monoclinic,
P2 (1)/c, final R indices [I > 2s(I)], R1 = 0.0827,
wR2 = 0.2345, R indices (all data): R1 = 0.1191,
wR2 = 0.2521, a = 15.8125 (15) Å, b = 11.7056 (11) Å,
c = 19.5084 (18) Å, b = 93.543 (2)°, V = 3604.0(6) Å3,
T = 293 (2) K, Z = 4. Reflections collected/unique: 18430/
6687 (Rint = 0.1120), number of observations [>2s(I)] 3630,
parameters, 464. Supplementary crystallographic data have
been deposited at the Cambridge Crystallographic Data
Centre: CCDC 738018.
Synlett 2010, No. 2, 227–230 © Thieme Stuttgart · New York

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