Cycloaddition reactions of phthalimide substituted cyclic polyenes with heteroatom dienophiles

Article abstract of DOI:10.1002/jhet.5570440334

(Chemical Equation Presented) The cycloaddition of 6-phthalimidobicyclo[5. 1.0]octa-2,4-diene and 7-phthalimido-1,3,5-cycloheptatriene with nitrosobenzene and with 4-phenyl-1,2,4-triazoline-3,5-dione each gave a single heterocyclic product. X-ray crystallographic analysis of 8a indicated the regio- and stereoselectivity of this cycloaddition.

Full text of DOI:10.1002/jhet.5570440334

May-Jun 2007
Cycloaddition Reactions of Phthalimide Substituted Cyclic Polyenes
with Heteroatom Dienophiles
719
Stephen S. Templina, Nathaniel J. Wallockb, Dennis W. Bennettc, Tasneem Siddiqueec,
Daniel T. Haworthb, and William A. Donaldsonb*
aDepartment of Chemistry, Cardinal Stritch University, 6801 N. Yates Road, Milwaukee, WI 53217 USA
bDepartment of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881 USA
cDepartment of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, 3210 N. Cramer St.,
Milwaukee, WI 53211-3029 USA
Received May 23, 2006
N
N
H
O
O
O
R
N
N
N
H
H
H
H
N
H
R N O
Ph
Ph
N
O
NPhth
O
H
NPhth
H
NPhth
The cycloaddition of 6-phthalimidobicyclo[5.1.0]octa-2,4-diene and 7-phthalimido-1,3,5-cyclo-
heptatriene with nitrosobenzene and with 4-phenyl-1,2,4-triazoline-3,5-dione each gave a single
heterocyclic product. X-ray crystallographic analysis of 8a indicated the regio- and stereoselectivity of this
cycloaddition.
J. Heterocyclic Chem., 44, 719 (2007).
ring structure by either C=C, N–O, or C–O bond cleavage
(Scheme I) [3, 4]. This methodology has been utilized for
the preparation of 2-amino-6-hydroxy-1,7-heptanedioic
acid [5a], 5-lipoxygenase inhibitors [4b], metabotropic
glutamate receptor II (mGluR II) agonist analogues [5b],
(+)-uracil polyoxin C [5c], and (+)-streptazoline [5d].
More recently, C–N bond cleavage of 2,4,6-triaza-3,5-
dioxotricyclo[5.2.1.02,6]decenes (4) has been reported
including asymmetric variants (Scheme I) [6].
INTRODUCTION
Cycloadditions of conjugated dienes such as
cyclopentadiene with heteroatom dienophiles, such as
nitroso compounds (1) and 4-phenyl-1,2,4-triazoline-
3,5-dione (PTAD, 2) have been known for more than a
half-century [1,2]. In particular, the derived 3-azo-2-
oxabicyclo[2.2.1]heptenes (3) have great synthetic
potential due to the versatile routes to open the bicyclic
There are few examples of the reaction of 1 with
cycloheptatrienes or cycloheptadienes [7,8]. For example,
cycloadducts of nitrosobenzene with the benzannulated
cycloheptatrienone, purpurogallin (5), have been
examined as mimetics for the antimalarial agent
artemisinin (Scheme II) [8]. While there are slightly more
examples of the reaction of PTAD with cycloheptadienes
[7b,9], the cycloaddition of 2 with cycloheptatrienes has
been extensively studied [10].
Scheme I
N–O
C–O
OH
N
H
cleavage cleavage
R
HO
N
R
O
O
Nu
3
O
C=C
cleavage
C–O
cleavage
R
N
O
HO2C
CO2H
OH
N
Scheme II
R
N
O
Nu
R
O
N
R
OMe
O
O
1
OMe
Ph
1, R = Ph
N
O
OMe
ref. 8
O
MeO
OMe
R
R
MeO
O
O
N
N
N
O
O
Ph
2
O
O
5
IC50 3–9 μM against
O
P. falciparum
O
N
O
H
O
Me
O
O
HN
N
C–N
cleavage
O
Ph
O
N
H
artemisinin
O
N
N
Ph
Me
Me
Me
H
4
O
Nu

720
S. Templin, N. Wallock, D. Bennett, T. Siddiquee, D. Haworth, W. Donaldson
Vol 44
As part of our interest in the preparation of mGluR II
ligands [11], we herein report on the cycloaddition of
cyclic polyenes 6 and 7 with heteroatom dienophiles. The
phthalimide substituted polyenes 6 and 7 were chosen
since this protected nitrogen substitutent would provide a
useful functionality for further elaboration.
RESULTS AND DISCUSSION
6-Phthalimidobicyclo[5.1.0]octa-2,4-diene (6) and 7-
phthalimido-1,3,5-cycloheptatriene (7) were prepared by
literature procedures [11a,12].
Reaction of 6 with
nitrosobenzene gave 8a (Scheme III). The 13C NMR
spectrum of 8a indicated that this compound consisted of
10 sp2 and 6 sp3 hybridized carbons, while the H NMR
1
Figure 1. ORTEP diagram of 8a with atomic numbering, showing 50%
probability ellipsoids for non-hydrogen atoms.
spectrum contained four signals due to cyclopropane
protons. In order to determine the structure of 8a
unambiguously an X-ray diffraction analysis of this
compound was undertaken. A drawing of the molecule
and the crystallographic numbering is given in Figure 1,
the experimental crystallographic data, and the structural
parameters are given in Tables 1–3. This reveals the
stereo- and regioselectivity of the cycloaddition product
as indicated. The bond lengths and bond angles of 8a are
similar to those of other 7-oxa-8-aza-bicyclo[2.2.2]octa-2-
enes and 8-oxa-9-aza-bicyclo[2.2.2]non-2-enes [13]. The
reaction of 6 with PhC(O)NO gave 8b, whose structure
Table 1
Crystal Data and Structure Refinement for 8a
Empirical formula
Formula weight
CCDC No.
C22H18N2O3
358.38
239646
Wavelength (Å)
Crystal system
Space group
0.71069
Monoclinic
P21/c
Unit cell dimensions
a (Å)
b (Å)
c (Å)
ꢁ, deg
9.426(5)
10.753(5)
17.161(5)
98.130(5)
1721.9(13)
4
1.382
0.093
0.3 x 0.2 x 0.15
2.18 to 25.00
4035/3026 [Rint = 0.0298]
–1 to 11, –1 to 12, –20 to 20
3026/0/317
0.994
R1 = 0.0434, wR2 = 0.0860
R1 = 0.0980, wR2 = 0.1089
0.152 and –0.180
1
Volume, Å3
Z
Calculated (density), g cm–3
Absorption coefficient, mm–1
Crystal size, mm
ꢂ range, deg
Reflections collected/unique
Range of h, k, l
was assigned on the basis of similarity of its H NMR
spectral data [14] with that of 8a.
Scheme III
9
H
10
PhN=O/CH2Cl2
R
or
1
N
H
H
H
5
O
6
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2s (I)]
R indices (all data)
PhCONH(OH)
NaIO4
DMF/CH2Cl2
NPhth
H
NPhth
6
8a, R = Ph (quant.)
8b, R = COPh (quant.)
Largest feature, e Å–3
8
9
Ph
5.94, 6.20 ppm) [15] match well with those of H-6, H-9
and H-10 of 8a (ꢀ, 5.28, 5.84, and 6.36 ppm), while the
signals for C-1, C-4 and C-5 of (ꢀ 73.6, 50.4, 64.1 ppm)
of 9a match well with those of C-1, C-5 and C-6 of 8a (ꢀ
73.8, 51.8, and 62.3 ppm).
1
Ph
N O
N
O
5
CH2Cl2
NPhth
H
R
7
9a, R = NPhth (44%)
9b, R = H (20%, Ref. 7a)
The products 8a and 8b represent cycloaddition of the
N=O bond to 6 in a regioselective fashion. This selectivity
is such that the oxygen adds to the diene carbon closest to
the phthalimide substitutent. It is anticipated that the
phthalimide group will act as an electron withdrawing
substituent, and thus diene/triene carbons proximal to this
group will bear a greater partial positive charge than those
more distant. This is qualitatively supported by Hartree-
Fock calculations of 6. Notably, the observed
regioselectivity is similar to that previously reported for
cycloaddition of nitrosobenzene with a variety of
substituted dienes [16]. Additionally, minimization of the
In comparison, the reaction of 7 with an excess of 1 (12
mol equiv.) did not go to completion after 6 days (40 °C).
Monitoring of the crude reaction mixture indicated the
presence of 9a (R = NPhth) and unreacted 7. After
purification 9a was obtained in 44% isolated yield (58%
BORSM). Notably, the reaction between 1 and the parent
cycloheptadiene is reported to give 9b (R = H) in low
yield [7c].
The structure of 9a was assigned by
comparison of its NMR spectral data with that of 8a. In
particular, the signals for H-5, H-8 and H-9 of 8a (ꢀ 5.35,

May-Jun 2007
Cycloaddition Reactions of Phthalimide Substituted Polyenes with
Heteroatom Dienophiles
721
Table 2.
Table 3.
Atomic Coordinates (x104) and
Equivalent Isotropic Displacement Parameters (Å2 x 103) for 8a
Selected bond lengths (Å) and bond angles (deg) for 8a
O(1)-C(12)
O(2)-C(7)
O(3)-N(1)
O(3)-C(10)
N(1)-C(1)
N(1)-C(15)
N(2)-C(7)
N(2)-C(12)
N(2)-C(11)
C(7)-C(22)
C(8)-C(9)
C(8)-C(15)
C(9)-C(10)
C(10)-C(11)
C(11)-C(13)
C(12)-C(16)
C(13)-C(14)
C(13)-C(18)
C(14)-C(15)
C(14)-C(18)
C(16)-C(17)
C(16)-C(22)
C(17)-C(19)
C(19)-C(20)
C(20)-C(21)
C(21)-C(22)
1.203(3)
1.213(3)
1.446(2)
1.472(3)
1.434(3)
1.478(3)
1.402(3)
1.407(3)
1.473(3)
1.482(3)
1.311(4)
1.502(4)
1.490(4)
1.539(3)
1.516(3)
1.487(3)
1.512(3)
1.498(4)
1.513(4)
1.507(4)
1.375(4)
1.378(3)
1.386(4)
1.380(4)
1.381(4)
1.385(3)
O(1)-C(12)-N(2)
O(1)-C(12)-C(16)
O(2)-C(7)-N(2)
O(2)-C(7)-C(22)
O(3)-N(1)-C(1)
126.0(2)
Atom
x
y
z
Ueq
127.9(2)
124.8(2)
128.6(2)
109.43(18)
109.63(18)
112.2(2)
103.7(2)
117.02(17)
107.9(2)
109.6(2)
114.8(2)
112.9(2)
117.2(2)
117.1(3)
114.7(2)
116.7(3)
117.5(2)
115.0(2)
121.9(2)
126.2(3)
123.4(2)
59.47(17)
60.43(18)
60.10(18)
120.5(3)
O(1)
O(2)
O(3)
N(1)
N(2)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
–3994(2)
–1155(2)
564(3)
–514(2)
800(2)
1150(2)
1866(2)
260(2)
1377(2)
1522(3)
1113(3)
552(4)
427(3)
841(3)
189(2)
689(3)
8004(1)
10235(1)
7815(1)
7096(1)
8990(1)
6544(1)
5739(2)
5223(2)
5498(2)
6291(2)
6815(2)
9813(1)
6679(2)
7237(2)
7975(2)
8559(1)
8685(1)
8238(2)
7423(2)
6829(2)
9371(2)
9406(2)
7628(2)
10141(2)
10808(2)
10778(2)
10042(1)
63(1)
57(1)
57(1)
45(1)
39(1)
42(1)
60(1)
66(1)
58(1)
57(1)
51(1)
42(1)
49(1)
49(1)
46(1)
41(1)
44(1)
46(1)
50(1)
45(1)
42(1)
53(1)
55(1)
60(1)
62(1)
55(1)
42(1)
O(3)-N(1)-C(15)
O(3)-C(10)-C(9)
O(3)-C(10)-C(11)
N(1)-O(3)-C(10)
N(1)-C(15)-C(8)
N(1)-C(15)-C(14)
N(2)-C(11)-C(13)
N(2)-C(11)-C(10)
C(1)-N(1)-C(15)
C(8)-C(9)-C(10)
C(8)-C(15)-C(14)
C(9)-C(8)-C(15)
C(9)-C(10)-C(11)
C(10)-C(11)-C(13)
C(11)-C(13)-C(14)
C(11)-C(13)-C(18)
C(13)-C(14)-C(15)
C(13)-C(14)-C(18)
C(13)-C(18)-C(14)
C(14)-C(13)-C(18)
C(15)-C(14)-C(18)
324(2)
–2271(2)
1189(3)
811(4)
1716(4)
2997(3)
3396(3)
2511(3)
–2033(3)
–1825(3)
–1476(3)
–597(3)
–1368(3)
–3477(4)
–2070(3)
–1920(3)
–1232(3)
–3970(3)
–5103(4)
–3367(3)
–5313(4)
–4401(4)
–3271(3)
–3084(3)
–134(3)
312(3)
1050(2)
–450(2)
2248(3)
2721(3)
1977(3)
–1077(2)
–1871(3)
2356(3)
–2307(3)
–1971(3)
–1164(3)
–719(2)
Scheme IV
N
N
14
13
H
O
O
N
O
7
N
steric interactions between the phenyl group of 1 and the
phthalimide group of 6 in the cycloaddition transition
state, may contribute to the observed regioselectivity [17].
For 9a (cycloadduct of 7 with 1), the regioselectivity is
the same as that reported for 9b, the cycloaddition product
from unsubstituted cycloheptatriene and 1 [7c].
H
H
Ph
2
N
Ph
11
H
NPhth
N
12
O
H
10 (80%)
NPhth
6
N
N
H
The cyclic polyenes 6 and 7 were treated dropwise
with a solution of 4-phenyl-1,2,4-triazoline-3,5-dione (2),
to afford 10 and 11 as crystalline solids (Scheme IV). The
structure of 10 was assigned by comparison of its NMR
spectral data with that for 8a. In particular, the signals for
H-7, H-11, H-12, H-13 and H-14 of 10 (ꢀ 5.19, 5.50, 4.88,
6.13, 6.54 ppm) are similar to those of H-1, H-5, H-6, H-
10 and H-9 of 8a (ꢀ 4.97, 5.28, 4.58, 5.84, and 6.36 ppm).
Additionally the NMR spectral data for 10 may be
compared to 12, the cycloadduct of homofulvene (13) and
2 (Equation I) [9d]. The signals for H-7, H-12, and H-
13/H-14 of 12 (ꢀ 5.07, 5.39, 6.04/6.26 ppm) are similar to
those of 10.
The symmetrical structure of 11 was assigned on the
basis of its NMR spectral data. In particular, the 1H NMR
spectrum of 11 consisted of four non-aromatic signals
while the 13C NMR spectrum consisted of 13 total signals,
three of which corresponded to sp3 hybridized carbons.
The relative stereochemistry about the cyclopropane
ring was assigned on the basis of the magnitude of H-H
O
NPhth
9
8
O
O
N
NPhth
N
7
N
Ph
N
Ph
H
10
H
O
H
11 (88%)
NPhth
H
15
Equation I
14
13
H
O
O
N
7
N
H
H
2
N
N
Ph
H
N
12
N
Ph
ref. 9d
O
O
14 (20%)
12 (32%)
13
coupling for these protons; the 2.3 Hz coupling between
the signals at ꢀ 2.55 (1H) and 2.42 (2H) are consistent
with their trans-disposition about the three-membered
ring. Product 11 arises via equilibration of 7 with its

722
S. Templin, N. Wallock, D. Bennett, T. Siddiquee, D. Haworth, W. Donaldson
Vol 44
and NaIO4 (1.96 g, 8.98 mmol) in CH2Cl2 (7.2 mL), DMF (7.2
mL) and water (3.6 mL) was added, over a period of 80 min, a
solution of benzohydroxamic acid (1.23 g, 8.97 mmol) in DMF
(3.6 mL). The reaction mixture was stirred for an additional 2 h,
then poured into water (30 mL) and extracted with CH2Cl2 (3 x
30 mL). The combined extracts were dried and concentrated.
The residue was purified by column chromatography (SiO2,
hexanes–ethyl acetate = 2:1 gradient) to afford 8b as a cream
colored solid (1.168 g, ~100%)(recrystallized from CH3CN), mp
202-203°; ir (KBr): 3100, 3071, CO 1769, 1713, 1650, 1387 cm–
bicyclo[4.1.0]heptadiene isomer 15 via 3,3-sigmatropic
rearrangement. Typical barriers for cycloheptatriene-
norcaradiene interconversion (ꢀG‡ ~ 2–12 kcal mol–1)
[18] are considerably lower than activation parameters for
cycloaddition with PTAD (ꢀG‡ ~ 17–20 kcal mol–1) [10e].
Thus, while the equilibrium between 7 ꢁ 15 lies far
toward 7 (no 15 detected by NMR spectroscopy),
apparently reaction of PTAD with 15 is more rapid than
with 7, and the dynamic equilibrium is siphoned off by
this cycloaddition.
1
1; H nmr (deuteriochloroform, 60°): ꢂ 0.69 (ddd, 1H, J = 5.2,
7.9, 9.7 Hz), 1.39 (br pent, 1H, J = 8.5 Hz), 1.80-1.66 (m, 2H),
4.53-4.50 (m, 1H), 5.21 (dd, 1H, J = 3.6, 7.8 Hz), 5.81 (br m,
1H), 6.23 (br t, 1H, J = 8.4 Hz), 6.46 (ddd, 1H, J = 1.2, 6.6, 9.0
Hz), 7.50-7.39 (m, 3H), 7.78-7.72 (m, 4H), 7.86 (d, J = 3.0, 5.4
Hz, 2H, phenyl protons); 13C nmr (deuteriochloroform): ꢂ 9.6,
13.6, 16.1, 51.6, 76.7, 77.1, 123.5, 128.0, 128.5, 128.9, 129.7,
130.3, 130.8, 132.1, 134.3, 168.2. Anal. Calcd. for C23H18N2O4:
C, 71.49; H, 4.70; N, 7.25. Found: C, 71.22; H, 4.70; N, 6.87.
4-Phthalimido-7-phenyl-7-azo-6-oxabicyclo[3.2.2]nona-2,8-
diene (9a). To a solution of nitrosobenzene (70 mg, 0.65 mmol)
in freshly distilled CH2Cl2 (2 mL), under N2 at room
temperature, was added cycloheptatriene 7 (120 mg, 0.51
mmol). The green solution was heated at reflux for 20 h, at
which time analysis of an aliquot by 1H NMR spectroscopy
indicated the reaction was ~25% complete. Additional
nitrosobenzene (600 mg, 5.6 mmol) was added and the reaction
mixture was heated at reflux for an additional 5 days. The
mixture was cooled and concentrated, and 1H NMR
spectroscopy indicated 9a and unreacted 7. The residue was
purified by column chromatography (SiO2, hexanes–ethyl
acetate = 4:1 –> pure ethyl acetate gradient) to give a tan solid
(77 mg, 44%). Recrystallization from hexanes–ethyl acetate
gave an analytically pure sample, mp 145.5-147°; ir (nujol): CO
In summary, the cycloaddition of 6 or 7 with hetero
dienophiles proceeded in a selective fashion to generate
polycyclic heterocycles 8-11. These structures provide a
rich variety of structural diversity, which could be of
further use in synthesis.
EXPERIMENTAL
1
All H NMR and 13C NMR spectra were recorded at 300 and
75 MHz respectively. Melting points were obtained on a Mel-
Temp melting point apparatus and are uncorrected. Elemental
analyses were obtained from Midwest Microlabs, Ltd.,
Indianapolis, IN.
Bicyclic diene 6 and cycloheptatrienyl phthalimide 7 were
prepared according to the literature methods [10a,11].
General Procedure for the Reaction of Phthalimide
substituted polyenes with Nitrosobenzene. To a solution of
nitrosobenzene (215 mg, 2.01 mmol) in freshly distilled CH2Cl2
(2 mL), under N2 at room temperature, was added bicyclic diene
5 (252 mg, 1.00 mmol). The green solution was stirred for 6 h
and then concentrated. The residue was purified by column
chromatography (SiO2, hexanes–ethyl acetate = 4:1 to 2:1
gradient) (362 mg, 100%).
1
1711, 1770 cm-1; H nmr (deuteriochloroform): ꢂ 4.23 (dd, 1H,
5-H, J = 5.1, 7.7 Hz), 5.35 (dd, 1H, 4-H, J = 5.3, 7.7 Hz), 5.75-
5.68 (m, 1H, 1-H), 5.99-5.88 (m, 3H, H-olefinic), 6.23-6.17 (m,
1H, 9-H), 7.04-6.98 (m, 1H, phenyl proton), 7.16-7.13 (m, 2H,
phenyl proton), 7.34-7.27 (m, 2H, phenyl proton), 7.72-7.69
(AA’BB’, 2H, phthalimide protons), 7.80-7.77 (AA’BB’, 2H,
phthalimide protons); 13C nmr (deuteriochloroform): ꢂ 50.4,
64.1, 73.6, 115.2, 123.0, 123.5, 126.7, 128.8, 129.1, 129.4,
130.3, 132.0, 134.4, 151.4, 168.2. Anal. Calcd. for C21H16N2O3:
C, 73.24; H, 4.68; N, 8.14. Found: C, 73.12; H, 4.82; N, 7.95.
General Procedure for the Reaction of Phthalimide
substituted polyenes with 4-Phenyl-1,2,4-triazoline-3,5-dione.
5-Phthalimido-8-phenyl-8-aza-7-oxatricyclo[4.2.2.02,4]dec-9-
ene (8a). To a solution of nitrosobenzene (215 mg, 2.01 mmol)
in freshly distilled CH2Cl2 (2 mL), under N2 at room
temperature, was added bicyclic diene 6 (252 mg, 1.00 mmol).
The green solution was stirred for 6 h and then concentrated.
The residue was purified by column chromatography (SiO2,
hexanes–ethyl acetate = 4:1 to 2:1 gradient) to give an off-white
solid (362 mg, 100%). Recrystallization from hexanes–ethyl
acetate afforded crystals suitable for X-ray diffraction, mp 128-
1
129°; ir (KBr): 3061, 3032, CO 1708, 1594, 1375 cm–1; H nmr
(deuteriochloroform): ꢂ 0.68 (ddd, 1H, 3-H, J = 5.2, 7.9, 9.5 Hz),
1.39 (pent, 1H, H-cyclopropyl, J = 8.5 Hz), 1.46-1.33 (m, 1H, H-
cyclopropyl), 1.65-1.57 (m, 1H, H-cyclopropyl), 1.79-1.68 (m,
1H, H-cyclopropyl), 4.62-4.55 (m, 1H, 6-H), 4.97 (ddd, 1H, 1-
H, J = 1.2, 6.1, 7.4 Hz), 5.28 (dd, 1H, 5-H, J = 4.4, 8.3 Hz), 5.84
(ddd, 1H, 9-H, J = 0.6, 7.3, 9.4 Hz), 6.36 (ddd, 1H, 10-H, J =
1.4, 6.6, 9.3 Hz), 7.00-6.92 (m, 1H, phenyl proton), 7.11-7.04
(m, 2H, phenyl protons), 7.29-7.21 (m, 2H, phenyl protons),
7.78-7.71 (m, 2H, phthalimide protons), 7.89-7.82 (m, 2H,
phthalimide protons); 13C nmr (deuteriochloroform): ꢂ 9.6, 13.8,
15.8, 51.8, 62.3, 73.8, 117.6, 122.3, 123.4, 126.2, 128.6, 128.7,
131.9, 134.2, 152.5, 168.5. Anal. Calcd. for C22H18N2O3: C,
73.73; H, 5.06; N, 7.82. Found: C, 73.85; H, 5.20; N, 7.75.
A
solution containing a slight excess of 4-phenyl-1,2,4-
triazoline-3,5-dione (2) dissolved in a minimal amount of ethyl
acetate/hexanes (1:1, ~1 mL) was added, dropwise with stirring,
to a solution of the bicyclic diene 5 (90 mg, 0.36 mmol), also
dissolved in a minimal amount of ethyl acetate/hexanes (1:1, ~3
mL), just until the red color of the triazolinedione persisted.
During the addition a white to off-white precipitate formed. The
mixture was stirred for an additional 30 min, then cooled to 0 °C
(ice/water bath). The precipitate was isolated by vacuum
filtration and washed with ice-cold ethyl acetate/hexanes (1:1) to
give the product 10 as colorless crystals (120 mg, 80%).
4-Phenyl-11-phthalimido-2,4,6-triaza-3,5-dioxotetracyclo-
[5.4.2.02,6.08,10]tridec-12-ene (10). This compound was obtained
as small needle-like white crystals, mp 129-129.5°; ir (nujol):
CO 1707, 1766 cm–1; 1H nmr (deuteriochloroform): ꢂ 0.74 (ddd,
8-Benzoyl-5-phthalimido-8-aza-7-oxatricyclo[4.2.2.02,4]dec-9-
ene (8b). To a rapidly stirring solution of 5 (754 mg, 3.00 mmol)

May-Jun 2007
Cycloaddition Reactions of Phthalimide Substituted Polyenes with
Heteroatom Dienophiles
723
[7] (a) Hart, H.; Ramaswami, S. K.; Willer, R. J. Org. Chem.
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1H, J = 5.1, 7.8, 11.3), 1.43 (br pent, 1H, J = 8.0 Hz), 1.78-1.63
(m, 2H), 4.88 (dd, 1H, J = 3.0, 6.7 Hz), 5.19 (dd, 1H, J = 3.0, 7.8
Hz), 5.50 (t, 1H, J = 6.7 Hz), 6.13 (dd, 1H, J = 7.8, 8.4 Hz), 6.54
(dd, 1H, J = 7.2, 8.7 Hz), 7.54-7.35 (m, 5H, phenyl protons),
7.91-7.76 (AA'BB'q, 4H, phthalimide protons); 13C nmr
(deuteriochloroform): ꢀ 10.0, 15.0, 16.5, 50.3, 51.4, 54.1, 123.7,
125.9, 126.4, 128.4, 129.8, 131.7, 131.8, 134.6, 152.2, 168.2.
Anal. Calcd. for C24H18N4O4: C, 67.60; H, 4.25; N, 13.14.
Found: C, 67.51; H, 4.19; N, 13.12.
4-Phenyl-9-phthalimido-2,4,6-triaza-3,5-dioxotetracyclo-
[5.3.2.02,6.08,10]dodec-11-ene (11). This compound was obtained
as colorless crystals (ethanol), mp 215-217°; ir (nujol): CO
1713, 1779 cm-1; 1H nmr (deuteriochloroform): ꢀ 2.42 (td, 2H, 8-
and 10-H, J = 2.3, 3.2, Hz), 2.55 (t, 9-H, 1H, J = 2.3 Hz), 5.45
(m, 1- and 7-H, 2H), 6.29 (dd, 2H, 11- and 12-H, J = 3.2, 3.8),
7.54-7.33 (m, phenyl protons, 5H), 7.75-7.72 (AA’BB’, 2H,
phthalimide protons), 7.86-7.83 ppm (AA’BB’, phthalimide
protons, 2H); 13C nmr (deuteriochloroform): ꢀ 12.8, 29.8, 52.1,
123.6, 125.7, 126.3, 128.5, 129.3, 131.3, 131.6, 134.5, 156.7,
168.1 ppm. Anal. Calcd. for C23H16N4O4: C, 66.99; H, 3.91; N,
13.58. Found: C, 66.73; H, 3.92; N, 13.25.
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Acknowledgement. Partial financial support for this work were
provided by the National Institutes of Health (Grant No. GM-
42641) and the Department of Education (Grant No.
P200A000228). S.S.T. thanks Cardinal Stritch University for a
sabbatical leave during which portions of this research were
accomplished.
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