Iridium- and rhodium-catalyzed [2+2+2] cycloadditions of diynes with maleimide: A new synthetic route to highly substituted phthalimides

Article abstract of DOI:10.1055/s-2008-1072746

The [2+2+2] cycloaddition of maleimide with α,ω-diynes in the presence of [IrCl(cod)]₂ or [RhCl(cod)]₂ and DPPE gives cyclohexadiene derivatives which are readily aromatized with DDQ or MnO ₂. This two-step procedure gives

Full text of DOI:10.1055/s-2008-1072746

1376
LETTER
Iridium- and Rhodium-Catalyzed [2+2+2] Cycloadditions of Diynes with
Maleimide: A New Synthetic Route to Highly Substituted Phthalimides
New
Synthetic
R
e
oute to H
i
o
ghly Substitu
n
ted Phthalim
a
ides rdo X. Alvarez, Bernard Bessières,* Jacques Einhorn*
Département de Chimie Moléculaire (SERCO), UMR-5250, ICMG FR-2607, Université Joseph Fourier, 301 Rue de la Chimie, BP 53,
38041 Grenoble, Cedex 9, France
Fax +33(4)76635983; E-mail: bernard.bessieres@ujf-grenoble.fr; E-mail: jacques.einhorn@ujf-grenoble.fr
Received 12 February 2008
Ar
O
O
Z
Abstract: The [2+2+2] cycloaddition of maleimide with a,w-
diynes in the presence of [IrCl(cod)]2 or [RhCl(cod)]2 and DPPE
gives cyclohexadiene derivatives which are readily aromatized with
DDQ or MnO2. This two-step procedure gives access to highly sub-
stituted phthalimides in good yields.
[2+2+2]
+
NH
Z
NH
Ar
Ar
O
O
Ar
Key words: alkyne cycloaddition, phthalimides, iridium, rhodium,
dehydrogenations
Ar
O
[O]
Z
NH
N-Hydroxyphthalimide (NHPI) has recently been recog-
nized as a valuable catalyst for the aerobic oxidation of
various organic compounds under mild conditions.1 The
major drawback of these catalytic processes is the rather
poor turnover number of NHPI, requiring typically 10
O
Ar
Scheme 1
mol% catalyst loading to obtain satisfactory conversions. Chalk mentioned that Ni(CO)2(PPh3)2 catalyzes the
We have recently discovered that some NHPI analogues [2+2+2] cycloaddition of two alkynes with N-substituted
exhibit improved catalytic properties, allowing a lower maleimide, but under his conditions, the corresponding
catalyst loading (typically 1–4 mol%). These NHPI ana- 1,3-cyclohexadiene gives a Diels–Alder adduct with a
logues have in common their highly substituted phthal- second molecule of maleimide. Cycloaddition of hexa-
imide backbone bearing two aryl substituents ortho to the 2,4-diyne and N-phenylmaleimide gave a more sterically
imide moiety.2 Further improvements in the catalyst load- hindered 1,3-cyclohexadiene, which did not form a Diels–
ing of NHPI-type oxidations are highly desirable. Conse- Alder adduct, but in this case the yield of the [2+2+2] cy-
quently, we decided to explore new simple and efficient cloaddition was rather poor.6a More recently, Itoh report-
synthetic pathways able to furnish diaryl-substituted ed the ruthenium-catalyzed cycloaddition of a,w-diynes
phthalimide backbones.
with N-phenylmaleimide, but in his case too, the primary
reaction was followed by a Diels–Alder reaction with a
second molecule of N-phenylmaleimide, furnishing the
Diels–Alder adduct as the sole product.6f Furthermore, we
haven’t found any report of the use of N-unsubstituted
maleimide for this type of reaction.
The [2+2+2] cyclotrimerization of alkynes has become a
powerful method to obtain highly substituted aromatics.
Numerous catalytic systems have been developed for the
intermolecular (three alkynes), partially intramolecular
(one diyne and one alkyne) or fully intramolecular (one
triyne) versions of this reaction, some of which are char- We report herein the [2+2+2] cycloaddition of a,w-di-
acterized by being tolerant to a broad variety of functional aryldiynes with N-unsubstituted maleimide, catalyzed by
groups.3 Comparatively, the [2+2+2] cycloaddition of two iridium or rhodium complexes. The air stable complex
alkynes and one alkene has been less explored, yet giving [IrCl(cod)]2 in combination with DPPE, has been reported
a concise access to valuable 1,3-cyclohexadiene patterns.4 to be highly efficient in the cycloaddition of diynes with
We became interested in this type of cycloaddition, using alkynes.7 The same combination has been used for the
a,w-diaryldiynes and maleimide, reasoning that the corre- [2+2+2] cycloaddition of diynes with alkenes, generally
sponding dihydrophthalimide cycloadduct should be a used in large excess.6f In our first attempt, diyne 1a was
good precursor of the fully aromatized diaryl phthal- refluxed in THF in the presence of one equivalent of ma-
imides (Scheme 1). These should, in turn, be easy to con- leimide 2, 5 mol% of [IrCl(cod)]2, and 10 mol% of DPPE.
vert into N-hydroxy derivatives.5
After three hours, cyclohexadiene 3a was isolated in 55%
yield, without any trace of the Diels–Alder overreaction
product (Table 1, entry 1). A longer reaction time did not
improve the yield of 3a. After this encouraging result,
screening of the reaction conditions was undertaken.
Changing THF to 1,4-dioxane led to a slight decrease in
the yield of 3a (50%, entry 2).
Some reports of alkyne-maleimide [2+2+2] cycloaddi-
tions can be found in the literature.6 In an early note,
SYNLETT 2008, No. 9, pp 1376–1380
x
x.
x
x.
2
0
0
8
Advanced online publication: 07.05.2008
DOI: 10.1055/s-2008-1072746; Art ID: D05408ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
New Synthetic Route to Highly Substituted Phthalimides
1377
Table 1 [2+2+2] Cycloaddition of 1a with Maleimide 2a
Table 2 [2+2+2] Cycloaddition of Various a,w-Diaryldiynes with
Maleimide
[IrCl(cod)]2
or
Ph
E
E
O
O
R
[RhCl(cod)]2
E
E
Z
+
NH
NH
[IrCl(cod)]2
or
DPPE
O
O
solvent, reflux
O
O
Ph
[RhCl(cod)]2
Ph
Ph
+
NH
Z
NH
1a
E = CO2Et
2
3a
DPPE
THF, reflux
O
O
R
R
Entry
Solvent
THF
Catalyst
Yield of 3a (%)b
R
1
2
[IrCl(cod)]2, DPPE
[IrCl(cod)]2, DPPE
[IrCl(cod)]2, DPPE
[IrCl(cod)]2, DPPE
[IrCl(cod)]2, DPPE
[IrCl(cod)]2, DPPE
[IrCl(cod)]2, DPPE
[IrCl(cod)]2, DPPE
55
50
35
35
45
0
1
2
3
1,4-dioxane
MTBE
EtOH
Entry Diyne
Z
R
Meth- Prod- Yield
oda
A
B
A
B
A
B
A
A
B
B
B
B
B
B
uct
3a
3a
3b
3b
3c
3c
3d
3e
3f
(%)b
87
95
58
81
62
67
78
99
92
95
98
95
97
95c
3
4
1
2
1a
1a
1b
1b
1c
1c
1d
1e
1f
(EtO2C)2C
H
5
acetone
toluene
CH2Cl2
THF
(EtO2C)2C
H
6
3
O
H
7
0
4
O
H
8
87c
63d
95c,d
5
CH2
H
9
THF
[RhCl(cod)]2, DPPE
[RhCl(cod)]2, DPPE
6
CH2
H
10
THF
7
(EtO2C)2C
4-MeO2C
4-MeO
4-HO
4-MeO2C
4-Cl
3-MeO
4-MeO
4-Me
a Unless otherwise indicated, reaction performed with 5 mol% of Ir or
Rh complex and 10 mol% of DPPE in refluxing THF for 3 h.
b Isolated yield.
8
(EtO2C)2C
9
O
O
O
O
O
O
c Reaction performed with 10 mol% of Ir or Rh complex and 20 mol%
of DPPE.
10
11
12
13
14
1g
1h
1i
3g
3h
3i
d Yield after 24 h reaction.
The lower yield obtained with methyl tert-butyl ether
(35%, entry 3) may be explained by the low solubility of
maleimide in this solvent. Interestingly the reaction can be
performed in a protic solvent such as EtOH (35% yield,
entry 4). Acetone can also be used, giving a yield of 45%
of 3a (entry 5). Contrastingly, no reaction occurred in tol-
uene or dichloromethane and the starting materials were
recovered unchanged (entries 6 and 7). Using THF as the
best solvent, a very good yield of 87% of 3a was obtained
when the amount of iridium catalyst was increased to 10
mol% and DPPE to 20 mol% (entry 8).
1j
3j
1k
3k
a Method A: 10 mol% of [IrCl(cod)]2 and 20 mol% DPPE in refluxing
THF for 3 h. Method B: 10 mol% of [RhCl(cod)]2 and 20 mol% DPPE
in refluxing THF for 24 h.
b Isolated yield of pure 3.11
c Reaction performed with 5 mol% of [RhCl(cod)]2 and 10 mol% of
DPPE.
catalyst and of DPPE resulted in an almost quantitative
Rhodium catalysts are also increasingly popular in the do-
main of [2+2+2] cycloaddition.1 The use of [RhCl(cod)]2,
associated with a water-soluble phosphine ligand, seems
to have been limited to alkyne cyclotrimerization in aque-
ous media8 and, to our knowledge, it has not been used
previously for the diyne–alkene [2+2+2] cycloaddition.
When in our previous experiments [IrCl(cod)]2 was re-
placed by [RhCl(cod)]2, cycloaddition proceeded well,
though at a slower rate, requiring typically 24 hours for
completion. Nevertheless, the reaction was very clean and
the yields improved when compared with the iridium-cat-
alyzed experiments: 5 mol% of [RhCl(cod)]2 along with
10 mol% of DPPE gave a 63% yield of 3a after a 24 hours
reflux in THF (entry 9). Doubling the amount of rhodium
yield of 3a (95% isolated, entry 10).9
With these results in hand, we next explored the scope of
the reaction by modifying the linker (Z) or the aryl part of
the a,w-diaryldiyne 110 (Table 2). Ether-linked 1b and
methylene-linked 1c diynes revealed the same trends as
the malonate-linked diyne 1a: rhodium-catalyzed cy-
cloadditions with maleimide were slower than their iridi-
um-catalyzed counterparts, but the isolated yields of
cyclohexadienes 3b and 3c were comparatively higher
(entries 1–6). Malonate-linked diynes functionalized on
the aromatic rings with electron-withdrawing (1d) and
electron-donating groups (1e) both gave cycloaddition
with maleimide under iridium catalysis, furnishing the
Synlett 2008, No. 9, 1376–1380 © Thieme Stuttgart · New York

1378
L. X. Alvarez et al.
LETTER
R
Table 3 Aromatization of 1,3-Cyclohexadienes 3
R
R
Z
1. [RhCl(cod)]2
DPPE, THF,
reflux, 24 h
O
O
O
O
+
NH
Z
NH
DDQ or MnO2
2. MnO2, reflux,
4 d
Z
NH
Z
NH
O
O
O
R
O
R
R
1
2
4
R
R
3
4
Scheme 2 One-pot [2+2+2] cycloaddition–aromatization
Entry
3
Z
R
4
Yield (%)a
corresponding cyclohexadienes 3d and 3e in 78% and
99% isolated yields (entries 7 and 8). A further explora-
tion of the behavior of various aryl-substituted ether-
linked diynes was undertaken. In all cases, the cyclohexa-
dienes (3f–k) have been isolated in excellent yields (en-
tries 9–14). Interestingly, the reaction is compatible with
free hydroxy and halogen substituents (entries 9 and 11).
Method Method
Ab
Bc
99
99
99
99
99
99
99
99
99
99
99
1
2
3a (EtO2C)2C
H
H
H
4a 98
4b 93
3b
3c
O
3
CH2
4c
4d
4e
4f
95
–
We next attempted the aromatization of the resulting 1,3-
cyclohexadienes 3 using DBU and air12 but no reaction
occurred. The use of Pd/C or Pt/C in refluxing THF was
also ineffective.13 Contrastingly, when purified 3a was re-
acted with one equivalent of DDQ in refluxing toluene,
smooth conversion into fully aromatized phthalimide 4a
was obtained, isolated with a 98% yield after aqueous
workup and chromatographic purification (Table 3, entry
1, method A). The same method was effective using vari-
ous diynes, giving yields of isolated phthalimides 4 rang-
ing from 87% to 98% (entries 2, 3, 7, 8, 10, 11). An even
more convenient aromatization reagent was MnO2.14
When 3a was refluxed in toluene in the presence of ten
equivalents of activated MnO2, complete aromatization
was achieved after 48 hours and a quantitative yield of an-
alytically pure 4a was obtained after simple filtration and
solvent evaporation (Table 3, entry 1, method B). The
same method was used for the aromatization of cyclo-
hexadienes 3b–k obtained previously. The corresponding
phthalimides 4b–k have all been isolated in quantitative
yields (entries 2–11).15 This last aromatization method has
finally been extended to a one-pot [2+2+2] cycloaddition–
aromatization procedure. After completion of the rhodi-
um-catalyzed [2+2+2] cycloaddition of diyne 1a with ma-
leimide in THF (Table 2, entry 2), MnO2 (10 equiv) was
added and the reaction mixture was refluxed for four days.
Workup gave phthalimide 4a in 90% isolated yield. Sim-
ilarly, one-pot cycloaddition–aromatization gave 4h al-
most quantitatively starting from diyne 1h and maleimide
(Scheme 2).
4
3d (EtO2C)2C 4-MeO2C
5
3e
3f
(EtO2C)2C 4-MeO
–
6
O
O
O
O
O
O
4-HO
–
7
3g
3h
3i
4-MeO2C
4-Cl
4g 98
4h 98
8
9
3-MeO
4-MeO
4-Me
4i
4j
–
10
11
3j
92
3k
4k 87
a Isolated yield of pure 4.16
b Method A: reflux of 3 in toluene with DDQ (1 equiv) for 24 h.
c Method B: reflux of 3 in toluene with MnO2 (10 equiv) for 48 h.
bones. Their transformation into new NHPI analogues is
under way. A more complete scope of the present ap-
proach is also being studied.
Acknowledgment
We thank the CNRS and the Université Joseph Fourier for financial
support (UMR-5250, ICMG FR-2607) and the University of Costa
Rica for a fellowship to L.X.A.
References and Notes
(1) For reviews, see: (a) Recupero, F.; Punta, C. Chem. Rev.
2007, 107, 3800. (b) Ishii, Y.; Sakaguchi, S. Catal. Today
2006, 117, 105. (c) Sheldon, R. A.; Arends, I. W. C. E. Adv.
Synth. Catal. 2004, 346, 1051. (d) Ishii, Y.; Sakaguchi, S.;
Iwahama, T. Adv. Synth. Catal. 2001, 343, 393.
(2) (a) Nechab, M.; Einhorn, C.; Einhorn, J. Chem. Commun.
2004, 1500. (b) Nechab, M.; Kumar, D. N.; Philouze, C.;
Einhorn, C.; Einhorn, J. Angew. Chem. Int. Ed. 2007, 46,
3080.
In summary, we have developed a new simple and effi-
cient iridium- and rhodium-catalyzed [2+2+2] cycloaddi-
tion of a,w-diaryldiynes with maleimide. The
corresponding 1,3-cyclohexadienes have been aromatized
readily using DDQ or MnO2. The whole sequence was
also amenable to a one-pot procedure, giving rise to a con-
venient synthesis of highly substituted phthalimide back-
Synlett 2008, No. 9, 1376–1380 © Thieme Stuttgart · New York

LETTER
New Synthetic Route to Highly Substituted Phthalimides
1379
(3) For recent reviews of alkyne cyclotrimerizations, see:
(a) Agenet, N.; Buisine, O.; Slowinski, F.; Gandon, V.;
Aubert, C.; Malacria, M. Org. React. 2007, 68, 1.
(b) Gandon, V.; Aubert, C.; Malacria, M. Chem. Commun.
2006, 2209. (c) Chopade, P. R.; Louie, J. Adv. Synth. Catal.
2006, 348, 2307. (d) Yamamoto, Y. Curr. Org. Chem. 2005,
9, 503. (e) Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J.
Org. Chem. 2005, 4741.
(4) For recent reports, see: (a) Tanaka, K.; Nishida, G.; Sagae,
H.; Hirano, M. Synlett 2007, 1426. (b) Shibata, T.;
Kawachi, A.; Ogawa, M.; Kuwata, Y.; Tsuchikama, K.;
Endo, K. Tetrahedron 2007, 63, 12853. (c)Tsuchikama, K.;
Kuwata, Y.; Shibata, T. J. Am. Chem. Soc. 2006, 128,
13686. (d) Kezuka, S.; Tanaka, S.; Ohe, T.; Nakaya, Y.;
Takeuchi, R. J. Org. Chem. 2006, 71, 543. (e) Kesuda, S.;
Okado, T.; Niou, E.; Takeuchi, R. Org. Lett. 2005, 7, 1711.
(f) Shibata, T.; Arai, Y.; Takara, Y. Org. Lett. 2005, 7, 4955.
(g) Wu, M.-S.; Rayabarapu, D. K.; Cheng, C.-H.
Tetrahedron 2004, 60, 10005. (h) Slowinski, F.; Aubert, C.;
Malacria, M. J. Org. Chem. 2003, 68, 378. (i) Tsukada, N.;
Sugawara, S.; Nakaoka, K.; Inoue, Y. J. Org. Chem. 2003,
68, 5961. (j) Shanmugasundaram, M.; Wu, M.-S.;
Jeganmohan, M.; Huang, C.-W.; Cheng, C.-H. J. Org.
Chem. 2002, 67, 7724. (k) Ikeda, S.; Kondo, H.; Arii, T.;
Odashima, K. Chem. Commun. 2002, 2422.
(15 mL) was added dropwise. The reaction mixture was
stirred at r.t. for 48 h under Ar. The reaction mixture was
poured into an aq soln of 10% HCl and was extracted with
Et2O. The organic phases were washed with H2O, brine, and
dried over Na2SO4. Evaporation of the solvent gave a brown
oil or solid from which the product was separated by column
chromatography over silica gel using a mixture of EtOAc–
pentane (1:1) to give the product 1 with analytical purity in
80–95% yield. All diynes 1 gave analytical and spectral data
in accordance with the structure.
(11) All cyclohexadienes 3 gave analytical and spectral data in
accordance with the structure.
Data for Products 3
Compound 3a: mp 171.5 °C. 1H NMR (400 MHz, CDCl3):
d = 8.08 (br s, 1 H), 7.28–7.43 (m, 10 H), 4.28 (s, 2 H), 4.17
(q, 2 H, J = 8.0 Hz), 4.03 (q, 2 H, J = 8.0 Hz), 3.15 and 3.08
(ABq, 4 H, J = 20.0 Hz), 1.21 (t, 3 H, J = 8.0 Hz), 1.08 (t, 3
H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3): d = 176.4,
170.9, 170.8, 138.5, 135.1, 128.4, 128.1, 127.7, 124.0, 61.9,
61.7, 58.3, 47.9, 39.5, 14.1, 14.0. IR (neat): 3153, 3052,
1779, 1751, 1697, 1574, 1493, 1235, 1183 cm–1. Anal. Calcd
for C29H27NO6: C, 71.74; H, 5.61; N, 2.88. Found: C, 71.48;
H, 5.66; N, 2.53.
Compound 3b: mp 253.5 °C (dec.). 1H NMR (400 MHz,
DMSO-d6): d = 11.36 (br s, 1 H), 7.29–7.42 (m, 10 H), 4.74
and 4.30 (ABq, 4 H, J = 13.2 Hz), 4.69 (s, 2 H). 13C NMR
(100 MHz, DMSO-d6): d = 177.8, 138.2, 135.2, 134.1,
128.1, 127.3, 122.7, 70.5, 46.2. IR (neat): 3148, 3058, 1774,
1712, 1574, 1494, 1182 cm–1. Anal. Calcd for C22H17NO3: C,
76.95; H, 4.99; N, 4.08. Found: C, 76.70; H, 5.10; N, 3.85.
Compound 3e: mp 205 °C. 1H NMR (400 MHz, CDCl3):
d = 8.18 (br s, 1 H), 7.29 (d, 4 H, J = 12.0 Hz), 6.94 (d, 4 H,
J = 12.0 Hz), 4.24 (s, 2 H), 4.18 (q, 2 H, J = 8.0 Hz), 4.05 (q,
2 H, J = 8.0 Hz), 3.84 (s, 6 H), 3.14 and 3.09 (ABq, 4 H,
J = 16.0 Hz), 1.22 (t, 3 H, J = 8.0 Hz), 1.09 (t, 3 H, J = 8.0
Hz). 13C NMR (75 MHz, CDCl3): d = 176.6, 171.0, 170.8,
159.0, 134.4, 130.9, 129.4, 123.1, 113.9, 61.9, 61.6, 58.4,
55.3, 47.8, 39.6, 14.1, 14.0. Anal. Calcd for C31H31NO8: C,
68.25; H, 5.73; N, 2.57. Found: C, 68.14; H, 5.66; N, 2.41.
(12) (a) Mori, N.; Ikeda, S.; Sato, Y. J. Am. Chem. Soc. 1999, 121,
2722. (b) Ikeda, S.; Watanabe, H.; Sato, Y. J. Org. Chem.
1998, 63, 7026. (c) Ikeda, S.; Mori, N.; Sato, Y. J. Am.
Chem. Soc. 1997, 119, 4779.
(l) Shanmugasundaram, M.; Wu, M.-S.; Cheng, C.-H. Org.
Lett. 2001, 3, 4233.
(5) Einhorn, C.; Einhorn, J.; Marcadal-Abbadi, C. Synth.
Commun. 2001, 31, 741.
(6) (a) Chalk, A. J. J. Am. Chem. Soc. 1972, 94, 5928.
(b) Zhou, Z.; Costa, M.; Chiusoli, G. P. J. Chem. Soc.,
Perkin Trans. 1 1992, 1399. (c) Tsuda, T.; Mizuno, H.;
Takeda, A.; Tobisawa, A. Organometallics 1997, 16, 932.
(d) Tsuda, T.; Tobisawa, A.; Mizuno, H.; Takeda, A. Chem.
Commun. 1997, 201. (e) Tsuda, T. J. Mol. Catal. A: Chem.
1999, 147, 11. (f) Yamamoto, Y.; Kitahara, H.; Ogawa, R.;
Kawaguchi, H.; Tatsumi, K.; Itoh, K. J. Am. Chem. Soc.
2000, 122, 4310. (g) For an example of cycloaddition of
three alkynes in the presence of a maleimide double bond,
see: Grigg, R.; Sridharan, V.; Wang, J.; Xu, J. Tetrahedron
2000, 56, 8967.
(7) Takeuchi, R.; Tanaka, S.; Nakaya, Y. Tetrahedron Lett.
2001, 42, 2991.
(8) Kinoshita, H.; Shinokubo, H.; Oshima, K. J. Am. Chem. Soc.
2003, 125, 7784.
(9) General Procedures for Iridium- and Rhodium-
Catalyzed [2+2+2] Diyne–Maleimide Cycloadditions
(Table 2)
Diyne 1 (0.25 mmol), [IrCl(cod)]2 or [RhCl(cod)]2 (0.025
mmol) and DPPE (0.050 mmol) were dissolved in degassed
THF (5 mL) under an Ar atmosphere and the mixture was
stirred at r.t. for 5 min. Maleimide (0.25 mmol) was then
added in one portion and the reaction mixture was refluxed
for 3 h in the case of iridum catalysis or 24 h in the case of
rhodium catalysis. After cooling, the resulting reaction
mixture was concentrated under reduced pressure and
cyclohexadiene 3 was isolated by column chromatography.
(10) General Procedure for the Preparation of Diynes 1 by
Sonogashira Coupling
(13) For classical aromatization reagents, see: Fu, P. P.; Harvey,
R. G. Chem. Rev. 1978, 78, 317.
(14) (a) Möller, B. S.; Undheim, K. Synth. Commun. 2003, 33,
4209. (b) For a review, see: Mashraqui, S.; Keehn, P. Synth.
Commun. 1982, 12, 637. (c) Fatiadi, A. J. Synthesis 1976,
65. (d) Fatiadi, A. J. Synthesis 1976, 133.
(15) General Procedure for Aromatization of
Cyclohexadienes 3
With DDQ: Cyclohexadiene 3 (0.15 mmol) and DDQ (0.15
mmol) were dissolved in anhyd toluene (5 mL) and the
reaction mixture was stirred under reflux for 24 h. Once
cooled, the resulting reaction mixture was washed with
distilled H2O, dried with Na2SO4, and evaporated under
reduced pressure. Phthalimide 4 was obtained after
chromatographical purification using SiO2.
With MnO2: Cyclohexadiene 3 (0.15 mmol) and activated
MnO2 (1.5 mmol) were added to anhyd toluene (5 mL). The
black suspension was stirred under reflux for 48 h or until
completion of the reaction (TLC monitoring). After cooling,
the solid was filtered off and the filtrate evaporated under
reduced pressure, giving pure 4 in quantitative yields.
An oven-dried flask was charged with the corresponding
aryl iodide (15 mmol), PdCl2(PPh3)2 (350 mg, 0.50 mmol),
anhyd CuI (38 mg, 0.2 mmol), dried Et3N (15 mL) and anhyd
THF (15 mL) under Ar. The mixture was then stirred at r.t.
for 10 min. Afterwards, a solution of the corresponding
diacetylene (5 mmol) in anhyd THF (15 mL) and dried Et3N
Synlett 2008, No. 9, 1376–1380 © Thieme Stuttgart · New York

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L. X. Alvarez et al.
LETTER
(16) All phthalimides 4 gave analytical and spectral data in
accordance with the structure.
H), 1.19 (t, 6 H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3):
d = 170.9, 166.9, 146.9, 136.5, 134.8, 129.1, 129.0, 128.5,
128.4, 62.2, 60.1, 40.3, 14.1. Anal. Calcd for C29H25NO6: C,
72.04; H, 5.21; N, 2.90. Found: C, 72.35; H, 5.59; N, 3.12.
Data for Product 4a
Mp 179.5 °C. 1H NMR (400 MHz, CDCl3): d = 7.57 (br s, 1
H), 7.38–7.51 (m, 10 H), 4.15 (q, 4 H, J = 7.2 Hz), 3.52 (s, 4
Synlett 2008, No. 9, 1376–1380 © Thieme Stuttgart · New York

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