The preparation of 7-substituted norbornadiene-2,3-dicarboxylic anhydrides and an experimental and theoretical study of their reactivity

Article abstract of DOI:10.1016/j.tet.2007.03.009

Four new substituted methano-bridged or heteroatom-bridged norbornadienomaleic anhydrides have been prepared and converted to sesquinorbornadiene anhydrides by reaction with cyclic 1,3-dienes. The versatility of parity reversal, in conjunction with N-substituent steric effects, has been used to produce all three possible stereoisomers of the N,O-sesquinorbornadiene anhydrides in separate, stereoselective cycloadditions. The anhydrides have been synthesized by cyclization of their diacids (in situ production) or by flash vacuum pyrolysis of their furan adducts (yielding crystalline products); further fragmentation occurs at these or higher temperatures to produce five-membered carbocyclic or heterocyclic anhydrides. Activation energies have been evaluated for the fragmentation and cycloaddition processes using DFT calculations (B3LYP/6-31G*) and these calculations correctly predict, which reaction can be intercepted at the norbornadienomaleic anhydride stage and preferred stereochemistry of cycloadducts.

Full text of DOI:10.1016/j.tet.2007.03.009

Tetrahedron 63 (2007) 4338–4346
The preparation of 7-substituted norbornadiene-2,3-dicarboxylic
anhydrides and an experimental and theoretical study
of their reactivity
y
y
*
Davor Margetic, Ronald N. Warrener, Guangxing Sun and Douglas N. Butler
ꢀ
Centre for Molecular Architecture, Central Queensland University, Rockhampton, Queensland 4702, Australia
Received 27 November 2006; revised 14 February 2007; accepted 1 March 2007
Available online 6 March 2007
Abstract—Four new substituted methano-bridged or heteroatom-bridged norbornadienomaleic anhydrides have been prepared and converted
to sesquinorbornadiene anhydrides by reaction with cyclic 1,3-dienes. The versatility of parity reversal, in conjunction with N-substituent
steric effects, has been used to produce all three possible stereoisomers of the N,O-sesquinorbornadiene anhydrides in separate, stereoselective
cycloadditions. The anhydrides have been synthesized by cyclization of their diacids (in situ production) or by flash vacuum pyrolysis of their
furan adducts (yielding crystalline products); further fragmentation occurs at these or higher temperatures to produce five-membered
carbocyclic or heterocyclic anhydrides. Activation energies have been evaluated for the fragmentation and cycloaddition processes using
DFT calculations (B3LYP/6-31G*) and these calculations correctly predict, which reaction can be intercepted at the norbornadienomaleic
anhydride stage and preferred stereochemistry of cycloadducts.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
to be the most powerful C]C dienophile capable of isola-
tion.5,7 The ease with which 4 adds cyclic 1,3-dienes (cyclo-
pentadiene and fulvenes) or five-membered heterocycles
(furan and pyrrole) at room temperature has allowed rapid
entry to a wide range of bridge-substituted oxasesquinorbor-
nadienes, many for the first time. The fact that reaction of
anhydride 4 can be achieved with thiophene under high pres-
sure at room temperature has allowed production of the first
sulfur-bridged sesquinorbornadiene.8
Alkene systems formed by sharing a common p-bond
between two dienophiles have been found to yield a class
of highly reactive dienophiles. This is particularly evident
in those, which include maleic anhydride as one component,
e.g., maleic anhydride with itself to give 1,1 maleic anhy-
dride with p-benzoquinone to give 2,2 and maleic anhydride
with norbornadiene or 7-oxanorbornadiene to give 33,4 or 4,
respectively5,6 (Fig. 1). In fact, the last mentioned compound
4 has been described in our previous paper where it is shown
2. Results and discussion
O
O
O
O
O
O
O
O
O
O
O
O
O
O
In this study, we discuss approaches to the synthesis of nor-
bornadiene-2,3-dicarboxylic anhydrides 7a–f modified at
the 7-position (aza, oxa, thia, isopropylidene, and adamantyl-
idene); reports on a high level computational and FVP study
on the propensity of norbornadienes 7a–f to undergo retro
Diels–Alder fragmentation to form carbocyclic and hetero-
cyclic anhydrides 8a–f and to demonstrate the power of
parity reversal and steric substituent control to form N,O-
bridged sesquinorbornadiene anhydrides covering all geo-
metrical types via individual, stereoselective cycloaddition
reactions.
O
O
O
O
1
2
3
4
Kanematsu, 1979 Edman, 1968
Sauer, 1967
Butler, 2000
Figure 1. Superdienophiles 1–4, formed by the formal fusion of two dieno-
philes at the p-bond.
Keywords: Dienophiles; Sesquinorbornadienes; Flash vacuum pyrolysis;
DFT calculations; Diels–Alder reaction; Retro Diels–Alder fragmentation.
* Corresponding author at present address: Laboratory for Physical Organic
Chemistry, Department of Organic Chemistry and Biochemistry, RuCer
Boskovic Institute, Bijenicka cesta 54, 10000 Zagreb, Croatia. Tel.:
+385 1 4561 008; fax: +385 1 4680 195; e-mail: margetid@emma.irb.hr
Present address: Molecular Architecture Section, Intelligent Polymer
Research Institute, The University of Wollongong, Northfields Avenue,
Wollongong, NSW 2522, Australia.
Our approach to the synthesis of norbornadiene-2,3-dicarbo-
cyclic anhydrides 7a–f was based on the flash vacuum pyrol-
ysis (FVP)9 of their respective furan adducts 5a–f (Scheme
1). Preferential loss of furan rather than the alternative dienes
in reaction 5/7 was predicted by smaller activation
ꢁ
ꢀ
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0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.009

D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
4339
(a)
O
X
X
O
O
FVP 2
-ethyne
O
S
O
FVP 1
- 6
-S
CO
O
7d
O
O
-furan 6
CO
C
O
CO
O
OC
OC
O
10
X
O
5
7
8
9d
Series a) X=CH2; b) X=O; c) X=NZ; d) X=S; e) X=C=CMe2; f) X=C=CAdamantyl
(b)
CO2H
NZ
NZ
Ac2O
adducts
(see Scheme 2)
Z=CO2CH2Ph
CO
O
+
CO2H
CO2H
N
Z
C
O
CO2H
12
11
13
7c
(c)
O
Ac2O
6
+
CO2R
CO
O
FVP
O
CO2R
15 R=H
14 R=CH3
CO
O
CO
C
O
OC
OC
7f
9f
O
5f
KOH
X-ray structure
(Figure 1)
major isomer
Scheme 1. Synthesis of norbornadiene-2,3-dicarboxylic anhydrides 7a–f.
energies obtained from B3LYP/6-31G* calculations. Retro
Diels–Alder reaction10 led to the production of the parent
anhydride 7a, mp 85–85 ꢀC (lit.3 mp 88–89 ꢀC) in 85% iso-
lated yield by FVP (325 ꢀC, 0.005 mbar) of the furan adduct
5a in only the second method reported for the preparation
and isolation of this compound. Given the simplicity of the
process and the ready availability of the starting materials,
this now constitutes the preferred route to 7a. The 1H
NMR spectrum of 7a (vinylic d 7.14, bridgehead d 4.08,
and methylene d 2.77) corresponded with that published,3
while the 13C NMR (not reported previously) exhibited
five resonances (d 47.7, 78.0, 142.6, 159.3, and 170.6) in
accord with its C2 symmetry. Reaction of 7a with furan 6
regenerated the adduct 5a, together with its isomers, in the
same ratio as that observed in the in situ method (vide
supra).5
trapping agent. Attempts to prepare the 7-N-Z-derivative 7c
by FVP of the adduct 5c were unsuccessful and led only to
the N-Z-derivative of pyrrole-3,4-dicarboxylic anhydride
8c and acetylene. In the case of the S-bridged system 7d,
pyrolysis of adduct 9d8 (370 ꢀC, 0.005 mbar) gave no
spectral support for the production of 7-thianorbornadiene
anhydride 7d in the crude pyrolyzate, however circumstan-
tial evidence for its formation came from the isolation of
phthalic anhydride 10 and spectral identification of furan
from the cold trap. It is clear from this result that loss of sul-
fur from the 7-thianorbornadiene anhydride 7d is preferred
to retro Diels–Alder ejection of acetylene.
In seeking an explanation for these varied FVP results, we
have conducted a quantum-chemical study using high level
DFT calculations (B3LYP/6-31G*).15 The transition states
(TS1) involved in the production of the norbornadiene-2,3-
dicarboxylic anhydrides 7a–c from their furan adducts
Similar FVP of the furan adduct 5e at 375 ꢀC yielded
7-isopropylidene-norbornadiene-2,3-dicarboxylic anhydride
1
7e,11 mp 127–128 ꢀC, in 57% isolated yield. The H NMR
of 7e contained three proton resonances (vinylic d 7.06,
bridgehead d 4.49, and methyl d 1.52), which is completely
consistent with the assigned structure, and further supported
by the seven-line 13C NMR (d 19.5, 48,2, 103.5, 142.6,
159.1, 164.1, and 168.3). FVP pyrolysis of the extended-
frame12 furan adduct 5f13 in the adamantylidene series at
380 ꢀC produced the corresponding anhydride 7f, in quanti-
tative yield. The 1H NMR of 7f contained five sets of proton
resonances (vinylic d 7.06, bridgehead d 4.50, and adaman-
tyl resonances: allylic d 2.47, saturated d 1.59–1.67, and
1.79–1.91). Similarly, FVP of exo,endo-furan adduct 9f
(X-ray, Fig. 2) produced anhydride 7f. These experiments
confirm that the stereochemistry of the adduct, e.g.,
exo,endo-adduct 9f or exo,exo-adduct 5f, is not critical for
successful thermolysis.
The 7-oxa derivative 7b was prepared by FVP of 5b as out-
lined in the previous paper5 and the oily product so obtained
was used immediately for cycloadditions with the 1,3-diene
Figure 2. Structure and crystal packing of 9f with 30% of anisotropic ther-
mal probability.14

4340
D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
Table 1. Activation energiesa for the retro Diels–Alder fragmentation reac-
tions 5a–c (and 9a–c) to 7a–c (Ea1) and 7a–c to 8a–c (Ea2) calculated using
B3LYP/6-31G* method
Z
N
X=CH2
CO
O
OC
TS1
TS2
C
O
34 %
O
18
O
X
O
Z
Z
Z
X
O
O
N
N
N
X=O
6
C
O
O
O
O
X
Ea2
O
O
Ea1
CO
O
CO
O
CO
O
OC
83 %
OC
3 %
OC
9c
16
17
5a–c
9a–c
7a–c
+
7c
traces
Z
Z
N
N
exo,exo-isomer
exo,endo-isomer
X=NZ
11
Z=CO2CH2Ph
Series (a) X¼CH2
Series (b) X¼O
31.3
31.2
33.2
29.2
30.6
31.1
52.4
37.9
32.3
CO
O
OC
22 %
Series (c) X¼NCO2Bn
19
Z
N
kcal molꢁ1
.
a
15 %
X=C=CMe2
CO
OC
5a–c (or 9a–c) and the related transition states (TS2) for the
fragmentation of 7a–c to their five-membered ring anhy-
drides 8a–c were fully optimized. It is found that the activa-
tion energy for the retro Diels–Alder loss of furan (Ea1)
remains very similar (29.2–33.2 kcal molꢁ1) for all three
substrates 5a–c (see Table 1). In contrast, the activation
energy (Ea2) for the loss of acetylene from the norborna-
diene-anhydrides drops from 52.4 kcal molꢁ1 for the parent
7a to 37.9 kcal molꢁ1 for the oxa-system 7b, and further to
32.3 kcal molꢁ1 for the aza-system 7c. As this activation
energy (Ea2) for the aza-system is less than the activation
(Ea1) for its formation from the exo,exo-fused stereoisomer
5c by 1 kcal molꢁ1, then the failure to intercept the inter-
mediate anhydride 7c is fully supported by the calculated
energetics of the two sequential reactions.
O
20
Scheme 2. Azasesquinorbornadiene anhydrides formed by the generation
and trapping of azanorbornadienomaleic anhydride 7c.
This NMR analysis is further confirmed by determination
of crystal structure (Fig. 3).
Reaction of 7c with an excess of furan gives three adducts:
exo,endo- 1:1 adduct 9c, together with 2:1 exo,endo;exo,exo-
bis-adduct 16 and exo,endo;exo,endo-bis-adduct 17. At
30 ꢀC, the olefinic proton resonances of the pyrrole side in
the 1H NMR spectrum of 1:1 adduct 9c are broad and sepa-
rated by 0.30 ppm; while on furan side by 0.06 ppm. This
reflects their relative position in regard to the N–CO bond,
which is undergoing slow rotation at this temperature. The
coalescence of olefinic signals at the zpyrrole side occurs at
63 ꢀC, and the activation energy DG for the N–CO bond
rotation has been calculated to be 67.8 kJ molꢁ1. Structure
of 9c was unequivocally confirmed by X-ray crystallography
(Fig. 3), while structures of adducts 16 and 17 are assigned
by 1D and 2D NMR spectroscopy.
An alternative route to adducts of norbornadiene anhydride,
e.g., furan 5a and 9a, was reported by Williams et al.,16 in
which the related norbornadiene dicarboxylic acid was
dehydrated to produce 7a in situ and trapped by warming
in acetic anhydride in the presence of cyclopentadiene. We
have now used this technique to form adducts of 7-(N-
benzyloxycarbonyl)norbornadienomaleic anhydride 7c and
7-adamantylidene norbornadienomaleic anhydride 7f. The
required dicarboxylic acids were prepared from the addition
of acetylene dicarboxylic acid to N-Z pyrrole (diethyl ether,
sealed tube, 65 ꢀC, 40%) to form 13 or hydrolysis of the
adduct of DMAD with 6,6-adamantylidenefulvene 14 to
access 15. A selection of new azasesquinorbornadiene anhy-
drides formed by the generation and trapping of various
pentacyclic dienes with norbornadienomaleic anhydride 7c
is presented in Scheme 2. All reactions are stereospecific
giving a single product at the anhydride olefinic bond.
High stereospecificity was observed in the reaction of 7c
with 6,6-dimethylfulvene, where exo,endo-adduct 20 was
formed as the single product in moderate yield (15%). Struc-
ture of 20 was deduced by NMR analysis and supported by
1
similarity of its H NMR spectrum to that of 9c. The most
indicative feature is the separation of olefinic protons
of the pyrrole and fulvene sides (0.26 and 0.07 ppm, respec-
tively). This result also indicated that cycloaddition of 7c
Dienophile 7c reacted with excess cyclopentadiene at 60 ꢀC
to produce exclusive 2:1 adduct 18. Formation of intermedi-
ate anhydride 9c could be deduced from the structure of the
final bis-adduct. The exo,endo-geometry on the unsubsti-
tuted part of 18 is revealed by the observation of the coupling
between endo- and bridgehead protons but not on the anhy-
dride side of molecule. The exo,endo-structure of the anhy-
dride side of 18 can be envisaged by similar chemical shifts
of the olefinic signals on both sides of adduct, and the lack of
steric compression effects of nitrogen.17 Owing to the steric
hindrance on both sides, the rotation of the central carbamate
N–CO bone is locked even at 60 ꢀC, causing the loss of sym-
Figure 3. Crystal structures of 18 and 9c with 30% of anisotropic thermal
probability.
1
metry and the duplication of the H and 13C NMR signals.

D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
4341
Table 2. B3LYP/6-31G* activation energies for Diels–Alder reactions of
7c with cyclic dienesa
product 19, was formed exclusively (Scheme 2). The sim-
1
plicity of the H NMR spectra of 19 at 60 ꢀC is indicative,
Z
Z
possessing three non-benzenoid resonances, is in full agree-
ment with its C2v symmetry. At room temperature, the sys-
tem suffers slow rotation about the bridge N–CO bond
causing signal broadening. Again, the crystal analysis con-
firms the geometry of 19 (Fig. 4).
N
X
N
X
CO
O
CO
O
OC
OC
X
exo,exo-
11.4
exo,endo-
This difference and the stereochemical outcome could be
easily predicted by DFT calculations at B3LYP/6-31G*
level. Transition state geometries of Diels–Alder reactions
of pentacyclic dienes (furan and 6,6-dimethylfulvene) with
dienophile 7c are illustrated in Figure 5. Calculated activa-
tion energies (Table 2) are in good agreement with experi-
ment: exo,endo-addition is favored for CPD, furan and
6,6-dimethylfulvene, while exo,exo-addition is predicted
for N-Z pyrrole reaction.
CH2
O
NZ
5a
5b
5c
5d
9a
9b
9c
9e
10.5
16.7
20.2
11.5
15.6
21.9
15.0
C]CMe2
kcal molꢁ1; Z¼CO2Me.
a
with 6,6-dimethylfulvene, although predicted to be the most
reactive (Table 2) is a less yielding reaction than with CPD
and furan, presumably due to smaller efficiency of isolation
process.
The availability of the new heterobridged dienophiles 7b and
7c has allowed a new set of parity reversal experiments5 to be
examined. As described above, the parity reversal reaction
was conducted on the N-Z compound 7c, which was
The opposite stereochemistry was obtained in the reaction of
N-Z pyrrole 11 and diene 7c. In this case, the exo,exo-
Figure 4. Structure and crystal packing of 19 with 30% of anisotropic thermal probability.
(b)
(a)
1.397
1.410
95.3
°
95.1
°
1.487
1.555
104.4
1.420
°
1.485
1.560
1.543 2.270
2.217
102.5
°
112.1°
1.544
111.1
1.363
°
1.478
1.379
Figure 5. Transition state for: (a) exo,exo-Diels–Alder reaction of 7c with furan, (b) exo,endo-Diels–Alder reaction of 7c with 6,6-dimethylfulvene, calculated
using B3LYP/6-31G* method.

4342
D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
generated in situ and reacted with furan 6 to form alternate
turn-frame adduct 9c as a major product (Scheme 2). Fur-
thermore, reaction of pyrrole 21 with 7-oxanorbornadiene-
maleic anhydride 7b produced a single adduct 27 in which
the heterobridges are syn-facially oriented (Scheme 3).
The stereoselectivity of this reaction can be changed by
attaching a bulky group onto the pyrrole nitrogen.6 Thus,
reaction of N-trityl pyrrole 24 with 7b allowed entry to the
isomeric turn-frame adduct 28. Interestingly, reactions of
N-TMS and N-i-Pr3Si substituted pyrroles 22 and 23 with
7b produced exo,exo-adduct 27, indicating the removal of
nitrogen protecting group from pyrroles in the course of
cycloaddition. Cleavage of 22 and 23 could not be stopped
by addition of bases such as triethylamine, potassium car-
bonate, and sodium hydrogencarbonate. The structures of
these adducts were assigned on the basis of proton chemical
shift data and comparisons with related model compounds of
established structure (27: vinylic d 6.81, 6.67, bridgehead
d 5.23, 4.48; 28: vinylic d 6.74, 6.56, bridgehead d 5.29,
4.79). In each case, high stereoselectivity was observed,
yet the combination of parity reversal methodology and ste-
ric control has allowed access to all three possible structures,
some with frame geometry not available by either individual
cycloaddition strategy. The ability to access adducts of for-
mal endo-cycloaddition origin, a cycloaddition selectivity
seldom observed in norbornene chemistry, makes the present
methodology a powerful synthetic strategy.
addition, density functional theory calculations (B3LYP/6-
31G*) were successfully used to evaluate activation energies
for the fragmentation processes and cycloaddition reactions.
These calculations correctly predict, which reactions can be
intercepted at the norbornadienomaleic anhydride stage and
experimentally observed stereospecificities of Diels–Alder
reactions with cyclic heterodienes.
4. Experimental details
4.1. General
Flash vacuum pyrolyses were conducted (100 mg scale)
under very high vacuum (0.005 mbar)19 in an unpacked
600ꢂ6 mm Pyrex tube heated by a horizontally-mounted
‘Termolyne’ model 21100 tube furnace (300–400 ꢀC). The
optimum pyrolysis temperature (calibrated using a thermo-
couple externally attached to the glass pyrolysis tube) was
determined separately for each substrate.
NMR spectra were recorded on a Bruker AMX-300 or
Bruker Avance DPX 400 NMR spectrometers. Spectra
were measured in CDCl3 with tetramethylsilane as an inter-
nal reference at 30 ꢀC unless indicated otherwise. Mass
spectrometry was conducted by Central Queensland Univer-
sity Analytical Laboratories using a Shimadzu QP200 mass
spectrometer or a Micromass Autospec instrument. Melting
points were determined on a Gallenkamp melting point ap-
paratus and are uncorrected. Microanalyses were performed
by CQUAL using a Fisons GSE EA 1108 microanalyser.
Column chromatography was carried out on Merck silica
gel 60 (180–230 mesh). Radial chromatography was per-
formed on the Chromatotron model 7924Twith Merck silica
gel 60 PF254 as absorbent. Petroleum ether (bp range 40–
60 ꢀC), ethyl acetate, and diethyl ether p.a. grade were
used as supplied. Substituted pyrroles, 6,6-adamantylidene-
fulvene,13 and compounds 5a,5 5e,5 9d,8 and 9e5 were
prepared according to literature. Other reagents are commer-
cially available (Aldrich) and were used without further
purification. Quantum-chemical calculations were per-
formed using Spartan program on a Silicon Graphics
R5000 workstation. For all structures, harmonic vibration
frequency calculations were performed to confirm whether
the obtained geometry represents a transition or minimum
energy structure.
R
N
O
O
7b
7b
24
RN
N
R
21-23
CO
CO
OC
OC
O
O
21 R=H
28 R=Tr
22 R=TMS
23 R=Si(i-Pr)3
24 R=Tr
25 R=TMS
26 R=Si(i-Pr)3
27 R=H
Scheme 3. Cycloaddition reactions of pyrroles with anhydride 7b.
The reactions described in Scheme 3 have demonstrated
extremely high dienophilicity of anhydride 7b, reacting
with unsubstituted pyrrole at room temperature, within
10 min. It is known that pyrrole itself is very poor diene.
To enhance its reactivity in Diels–Alder cycloadditions
N-electron-withdrawing substituents are required, in con-
junction with various physical and catalytic methods includ-
ing high pressure, ultrasound, and Lewis acid catalysis.18
4.1.1. (1a,2b,3a,6a,7b,8a)-11,12-dioxazatetracyclo-
[6.2.1.13,6.02,7]dodeca-4,9-diene-2,7-dicarboxylic anhy-
dride (5b). A mixture containing (1a,2b,3a,6a,7b,8a)-
11,12-dioxazatetracyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-2,7-
dicarboxylic acid20 (400 mg, 1.60 mmol), triethyl amine
(0.5 mL), and acetic anhydride (5.0 mL) was stirred at
60 ꢀC overnight. Volatiles were removed by evaporation
in vacuo and brown colored residue purified by two-fold
recrystallization from ethyl acetate. Anhydride 5b was
obtained as a yellow colored needles (270 mg, 73%), mp
3. Conclusion
New heteroatom-bridged norbornadienomaleic anhydrides
have been synthesized from their diacids or by flash vacuum
pyrolysis of their furan adducts. Further fragmentation
occurs at these or higher temperatures to produce five-
membered carbocyclic or heterocyclic anhydrides. These
heteronorbornadienomaleic anhydrides have been converted
to sesquinorbornadiene anhydrides by reaction with (het-
ero)cyclic 1,3-dienes, showing high reactivity. The versatil-
ity of parity reversal, in conjunction with N-substituent steric
effects, enabled the production of all three possible stereo-
isomers of the N,O-sesquinorbornadiene anhydrides. The
structures of all new adducts were assigned on the basis
of NMR spectroscopy and crystallographic analysis. In
1
183–184 ꢀC, lit.21 184–185 ꢀC. H NMR (CDCl3) d 5.30
(4H, t, J¼0.9 Hz, H1,3,6,8), 6.77 (4H, t, J¼0.9 Hz,
H4,5,9,10).
4.1.2. (1a,2b,3a,6a,7b,8a)-11-Isopropylidene-12-oxate-
tracyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-2,7-dicarboxylic

D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
4343
anhydride (5e). Mp 164–165 ꢀC. 1H NMR (CDCl3) d 1.61
(6H, s, CH3), 3.78–3.80 (2H, m, H9,10), 4.99–5.01 (2H,
m, H3,6), 6.56–6.60 (2H, m, H4,5), 6.71–6.73 (2H, m,
H9,10). 13C NMR (CDCl3) d 19.9, 46.7, 71.9, 81.7, 113.6,
139.5, 140.4, 145.1, 170.0. IR (KBr, cmꢁ1): 1760.
HRMS(EI) (M+) C16H14O4 requires m/z 270.0892, found
270.0891.
s, H3,6), 6.58 (2H, t, J¼1.5 Hz, H4,5), 6.72 (2H, s,
H9,10). 13C NMR (CDCl3) d 28.3, 28.4, 34.1, 37.1, 37.7,
38.3, 45.8, 72.0, 81.6, 128.4, 138.2, 139.6, 140.7, 170.2.
IR (KBr, cmꢁ1): 1776 (C]O). HRMS(EI) (M+) C23H22O4
requires m/z 362.1518, found 362.1515. Compound 9f mp
198–201 ꢀC. 1H NMR (CDCl3) d 1.60–2.00 (12H, m,
AdH), 2.35–2.38 (2H, m, AdH1,2), 3.42 (2H, s, H1,8),
5.16 (2H, s, H3,6), 6.35 (2H, s, H4,5), 6.60 (2H, t,
J¼1.5 Hz, H9,10). 13C NMR (CDCl3) d 18.8, 28.3, 33.8,
36.8, 37.2, 38.9, 42.8, 70.4, 82.7, 129.4, 138.7, 135.0,
141.0, 173.0. IR (KBr, cmꢁ1): 1770 (C]O). HRMS(EI)
(M+) C23H22O4 requires m/z 362.1518, found 362.1516.
4.1.3. 7-Oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxy-
lic anhydride (7b). Anhydride 7b was obtained by flash
vacuum pyrolysis of anhydride 5b (100 mg, 0.43 mmol) at
360ꢃ5 ꢀC and 0.005 mbar. Product deposits at cooler parts
of pyrolysis tube, as pale yellow oil (20 mg, 28%). It was
washed from the tube with CDCl3 and used immediately.
1H NMR (CDCl3) d 5.80 (2H, s, H1,4), 7.30 (2H, s, H5,6).
4.1.7. 7-Benzyloxycarbonyl-bicyclo[2.2.1]hepta-2,5-di-
ene-2,3-dicarboxylic acid (13). A solution of N-Z pyrrole
11 (2.00 g, 10 mmol) and acetylene dicarboxylic acid 12
(1.20 g, 11 mmol) in diethyl ether (10 mL) was heated at
60 ꢀC in a sealed tube for 6 days. The adduct 13 was formed
in 22% conversion yield determined by 1H NMR and used in
4.1.4. (1a,2b,3a,6a,7b,8a)-11-Dibenzyloxycarbonyl-11-
aza-12-oxatetracyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-
2,7-dicarboxylic anhydride (5c). N-Z pyrrole 11 (50 mg,
0.25 mmol) was added to a solution of anhydride 7b
(20 mg, 0.12 mmol) in CDCl3 (1 mL). The reaction was
allowed to stand at room temperature for 5 min. Radial chro-
matography (Et2O/petroleum ether) afforded the adduct 5c
(30 mg, 67%), which was crystallized from Et2O/petroleum
ether as colorless crystals. Mp 121–123 ꢀC. 1H NMR
(CDCl3) d 5.04 (1H, d, J¼12.0 Hz), 5.10 (1H, d, J¼
12.0 Hz) (CH2Ph), 5.11 (1H, s, H1), 5.12 (1H, s, H1), 5.25
(1H, s, H3), 5.30 (1H, s, H6), 6.73–6.74 (4H, m,
H4,5,9,10), 7.34–7.38 (5H, m, Ph). 13C NMR (CDCl3)
d 62.5, 62.5 (C1,8), 68.1 (CH2Ph), 72.9, 73.3 (C2,7), 81.8,
82.0 (C3,6), 128.9, 129.0, 129.2 (C20,30,40 of Ph), 140.6,
140.6, 140.8, 141.1 (C4,5,9,10), 152.9 (CO2Bn), 168.1,
168.3 (CO of anhydride). IR (KBr, cmꢁ1): 1766
(C]OAnh), 1707 (C]OBn). HRMS C20H15NO6 requires
m/z 365.0899, found 365.0899.
1
the next reaction step without isolation. H NMR (CDCl3)
d 5.09 (2H, s, PhCH2), 5.73 (2H, t, J¼1.3 Hz, H1,4), 7.18
(2H, br s, H5,6), 7.19–7.22 (5H, m, Ph).
4.1.8. Dimethyl-7-adamantylidene-bicyclo[2.2.1]hepta-
2,5-diene-2,3-dicarboxylate (14). A solution of 6,6-ada-
mantylidenefulvene13 (1.00 g, 5.05 mmol) and dimethyl
dicarboxylate (2.99 g, 14.08 mmol) in chloroform (20 mL)
was refluxed overnight. Solvent was removed in vacuo to
afford dark colored oil. Flash column separation (silica,
petroleum ether/ethyl acetate 5:1) afforded yellow colored
oil. Compound 14 was obtained as a colorless solid by treat-
ment with diethyl ether/petroleum ether (1.36 g, 80%) mp
156–158 ꢀC. 1H NMR (CDCl3) d 1.45–1.86 (12H, m,
AdH), 2.46 (2H, s, AdH), 3.81 (6H, s, CH3), 4.41 (2H, t,
J¼1.90 Hz, H1,4), 6.98 (2H, t, J¼1.90 Hz, H4,5). 13C
NMR (CDCl3) d 28.3, 32.2, 37.1, 38.1, 38.2 (C30), 51.9
(C10), 52.0 (C1,4), 52.6 (CH3), 115.2 (C7,20), 142.5 (C5,6),
152.1 (C5,6), 155.5 (C2,3), 166.1 (C]O). IR (KBr,
cmꢁ1): 1741 (C]O). HRMS C21H24O4 requires m/z
340.1674, found 340.1675.
4.1.5. 7-Adamantylidene-bicyclo[2.2.1]hepta-2,5-diene-
2,3-dicarboxylic anhydride (7f). FVP of adduct 5f
(100 mg, 0.28 mmol) at 380 ꢀC gave anhydride 7f as a color-
less solid (29 mg, 35%), which was used in the next reaction
1
without purification. Mp 124–125 ꢀC. H NMR (CDCl3)
d 1.59–1.67 (10H, m, AdH), 1.79–1.91 (2H, m, AdH), 2.47
(2H, s, AdH1,2), 4.50 (2H, s, H1,4), 7.06 (2H, s, H5,6).
13C NMR (CDCl3) d 28.4, 28.5, 32.7, 37.2, 38.5, 38.6,
48.0, 119.0, 143.6, 158.3, 159.7, 169.1.
4.1.9. 7-Adamantylidene-bicyclo[2.2.1]hepta-2,5-diene-
2,3-dicarboxylic acid (15). Diester 14 (2.63 g, 8 mmol)
was dissolved in methanol (5 mL), and a solution of 10%
aqueous potassium hydroxide (30 mL) was added. Reaction
mixture was stirred for 12 h at room temperature. Solvent
was removed in vacuo, residue taken up in water (20 mL)
and acid 15 precipitated by careful addition of concentrated
hydrochloric acid as a colorless solid (1.32 g, 53%), which
was used in next reaction without further purification. Ob-
4.1.6. (1a,2b,3a,6a,7b,8a)-11-Adamantylidene-12-oxa-
tetracyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-2,7-dicarb-
oxylic anhydride (5f) and (1b,2b,3a,6a,7b,8b)-11-
adamantylidene-12-oxatetracyclo[6.2.1.13,6.02,7]dodeca-
4,9-diene-2,7-dicarboxylic anhydride (9f). The dicarboxy-
lic acid 14 (380 mg, 1.1 mmol) was dissolved in acetic anhy-
dride, then furan (3.0 g, 44 mmol) was added. The mixture
was placed in a sealed vessel, heated to 65–70 ꢀC and left
stirring for 4 h. Excess furan and acetic anhydride were re-
moved in vacuo and the residue was then placed on a column
of silica gel. Further separation by radial chromatography
using 20:1 petroleum ether, with the solvent polarity gradu-
ally increased to ethyl acetate, gave two products, in order of
elution 9f (41 mg, 10%) and 5f (186 mg, 46%). The products
(both isomers) were white crystals. Compound 5f mp 211–
1
tained from crude spectrum H NMR (CDCl3) d 2.01–2.78
(16H, m, AdH, H1,4), 7.31 (2H, s, H5,6).
4.1.10. (1a,2b,3b,6b,7b,8a)-11-Benzyloxycarbonyl-11-
aza-12-oxatetracyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-
2,7-dicarboxylic anhydride (9c), (1a,2b,3b,6b,7b,8a,9-
b,10a,13a,14b)-15-benzyloxycarbonyl-15-aza-16,17-di-
oxahexacyclo[6.6.1.13,6.110,13.02,7.09,14]heptadeca-4,11-
diene-2,7-dicarboxylic anhydride (16) and (1a,2b,-
3b,6b,7b,8a,9b,10b,13b,14b)-15-benzyloxycarbonyl-
15-aza-16,17-dioxahexacyclo[6.6.1.13,6.110,13.02,7.09,14
]
and heptadeca-4,11-diene-2,7-dicarboxylic anhydride
(17). Furan (2 mL, 29 mmol) was added to a mixture of
1
214 ꢀC. H NMR (CDCl3) d 1.60–1.95 (12H, m, AdH),
2.54–2.56 (2H, m, Ad H1,2), 3.77 (2H, s, H1,8), 4.98 (2H,

4344
D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
diacid 13 (300 mg, 0.52 mmol) and acetic anhydride (2.0 g,
19.6 mmol). The mixture was stirred at 60 ꢀC overnight. The
reaction was separated by column chromatography (Et2O) to
afford in the order of elution: mono-adduct 9c (120 mg,
63%), exo,endo;exo,exo-bis-adduct 16 (10 mg, 4%) and
a mixture of 16 and exo,endo;exo,endo-bis-adduct 17 (trace),
all of which were crystallized from diethyl ether. Compound
9c mp 147–148 ꢀC. 1H NMR (CDCl3) d 4.78 (1H, s, H1 or
H8), 4.83 (1H, s, H8 or H1), 4.98 (1H, d, J¼12.0 Hz,
CHaHbPh), 5.15 (1H, d, J¼12.0 Hz, CHaHbPh), 5.19 (1H,
s, H3 or H6), 5.22 (1H, s, H6 or H3), 6.18 (1H, d, J¼
4.8 Hz, H4 or H5), 6.48 (1H, d, J¼4.8 Hz, H5 or H4), 6.72
(1H, s, H9 or H10), 6.78 (1H, s, H10 or H9), 7.31–7.40
(5H, m, Ph). 13C NMR (CDCl3) d 59.7, 59.8 (C1,8), 68.2
(CH2Ph), 70.6, 71.5 (C2,7), 83.0, 83.1 (C3,6), 128.9,
129.3, 129.3 (C203040 of Ph), 136.4 (C10 of Ph), 134.7,
135.0 (C4,5), 140.6, 141.8 (C9,10), 152.4 (CO2Bn), 170.8
(carbonyl of anhydride). IR (KBr, cmꢁ1): 1758 (C]
OAnh), 1706 (C]OBn). HRMS requires C20H15NO6 m/z
365.0899, found 365.0904. Anal. calcd for C20H15NO6: C,
65.74; H, 4.14; N, 3.84. Found C, 65.85; H, 4.15; N,
J¼5.5, 3.2 Hz, H4), 6.08 (1H, dd, J¼5.5, 3.2 Hz, H5),
7.36–7.39 (5H, m, Ph). 13C NMR (CDCl3) d 46.3, 46.4
(C10,13), 47.1, 48.0 (C9,14), 49.8, 49.9, 50.0, 52.4
(C3,6,16,17), 59.6, 60.0 (C1,8), 67.5 (CH2Ph), 69.75, 70.5
(C2,7), 129.3, 129.3, 129.6 (C203040 of Ph), 132.8, 133.2,
134.1, 134.4 (C4,5,11,12), 136.9 (C10 of Ph), 152.5
(CO2Bn), 173.1, 173.2 (carbonyl of anhydride). IR (KBr,
cmꢁ1): 1761 (C]OAnh), 1703 (C]OBn). HRMS
C26H23NO5 requires m/z 429.1576, found 429.1576
(91.5%), 338.1 (7.5), 294.1 (61.0), 272.1 (32.0), 228.1
(100), 184.1 (60.0), 156.1 (21.8), 128.1 (10.0). Anal. calcd
for C26H23NO5: C, 72.7; H, 5.40; N, 3.26. Found C, 72.61;
H, 5.39, N, 3.25%.
4.1.12. (1a,2b,3a,6a,7b,8a)-11,12-Dibenzyloxycarbonyl-
11,12-diazatetracyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-
2,7-dicarboxylic anhydride (19). A mixture containing
diacid 13 (200 mg, 0.64 mmol) and N-Z pyrrole 11
(260 mg, 1.3 mmol) in acetic anhydride (2.2 g, 21.6 mmol)
was stirred at 80 ꢀC overnight. The reaction was purified
by column chromatography (Et2O/petroleum ether 1:1) to
afford the product 19, which was crystallized from benzene
(70 mg, 22%), mp 147 ꢀC (colorless crystals). 1H NMR
(CDCl3) d 4.84 (2H, br s, two of CH2Phꢂ2), 5.02 (2H, br
s, two of CH2Phꢂ2), 5.20 (4H, s, H1,3,6,8), 6.71 (2H, s,
two of H4,5,9,10), 6.76 (2H, s, two of H4,5,9,10), 7.33–
1
3.82%. Compound 16 mp 168–170 ꢀC. H NMR (CDCl3)
d (1H, d, J¼6.0 Hz, H9), 2.04 (1H, d, J¼6.0 Hz, H14),
4.39 (1H, s, H1), 4.81 (1H, s, H8), 4.81 (1H, s, H10), 4.94
(1H, s, H13), 4.95 (1H, d, J¼12.0 Hz, CHaHbPh), 5.12
(1H, d, J¼12.0 Hz, CHaHbPh), 5.24 (1H, s, H3), 5.28 (1H,
s, H6), 6.12 (1H, dd, J¼5.8, 1.7 Hz, H4), 6.38 (1H, dd,
J¼5.8, 1.6 Hz, H12), 6.41 (1H, dd, J¼5.8, 1.6 Hz, H11),
6.44 (1H, dd, J¼5.8, 1.7 Hz, H5), 7.32–7.40 (5H, m, Ph).
13C NMR (CDCl3) d 47.5, 47.7 (C9,14), 58.4, 58.7 (C1,8),
67.9 (CH2Ph), 68.8, 69.8 (C2,7), 81.3, 81.4 (C10,13), 83.8,
83.9 (C3,6), 129.1, 129.1, 129.3 (C203040 of Ph), 134.9,
134.9 (C4,5), 136.9 (C10 of Ph), 138.3, 138.6 (C11,12),
153.7 (CO2Bn), 171.3 (carbonyl of anhydride). IR (KBr,
cmꢁ1): 1756 (C]OAnh), 1701 (C]OBn). HRMS
C24H19NO7 requires m/z 433.1161, found 433.1162. Com-
pound 17 obtained from crude spectrum. 1H NMR
(CDCl3) d 2.58 (1H, d, J¼6.5 Hz, H9), 2.62 (1H, d, J¼
6.5 Hz, H14), 4.13 (1H, s, H1), 4.21 (1H, s, H8), 4.85 (1H,
m, H10), 4.90 (1H, m, H13), 5.01 (1H, d, J¼11.8 Hz,
CHaHbPh), 5.08 (1H, d, J¼11.8 Hz, CHaHbPh), 5.19 (1H,
m, H3), 5.24 (1H, m, H6), 5.80 (1H, dd, J¼5.8, 1.6 Hz),
5.92 (1H, dd, J¼5.8, 1.7 Hz), 6.16 (1H, dd, J¼5.8,
1.7 Hz), 6.35 (1H, dd, J¼5.8, 1.7 Hz, H4,5,11,12), 7.30–
7.40 (5H, m, Ph).
1
7.36 (10H, m, Phꢂ2). H NMR (CDCl3, 60 ꢀC) d 4.94
(4H, br s, CH2Phꢂ2), 5.18 (4H, s, H1,3,6,8), 6.72 (4H, s,
H4,5,9,10), 7.24–7.31 (10H, m, Phꢂ2). 13C NMR (CDCl3,
30 ꢀC) d 63.3 (C1,3,6,8), 68.5 (CH2Ph), 71.2 (C3,7),
129.1, 129.2 (C203040 of Ph, two overlapped), 136.3 (C10
of Ph), 141.2, 141.9 (C4,5,9,10), 154.2 (CO2Bn), 168.4 (car-
bonyl of anhydride). IR (KBr, cmꢁ1): 1771 (C]OAnh),
1711 (C]OBn). LRMS (m/z) 499 (M+H, 13.2%), 319
(15.0), 297 (21.9), 201 (76.2), 157 (100). Anal. calcd for
C28H22N2O7: C, 67.45; H, 4.45; N, 5.62. Found C, 67.15;
H, 4.42; N, 5.61%.
4.1.13. (1a,2b,3b,6b,7b,8a)-11-Benzyloxycarbonyl-12-
isopropylidene-11-azatetracyclo[6.2.1.13,6.02,7]dodeca-
4,9-diene-2,7-dicarboxylic anhydride (20). 6,6-Dimethyl-
fulvene (200 mg, 1.9 mmol) was added to a mixture of
diacid 13 (248 mg, 0.83 mmol) and acetic anhydride (3.0 g,
39.0 mmol). The mixture was stirred at 60 ꢀC overnight.
Column chromatography (CH2Cl2) afforded mono-adduct
20, which was crystallized from CH2Cl2/petroleum ether
as colorless crystals (50 mg, 15%), mp 124–125 ꢀC. 1H
NMR (CDCl3) d 1.51 (6H, s, CH3), 3.80 (1H, s, H3), 3.83
(1H, s, H6), 4.84 (1H, s, H1), 4.89 (1H, s, H9), 4.98 (1H,
d, J¼12.1 Hz, CHaHbPh), 5.14 (1H, d, J¼12.1 Hz,
CHaHbPh), 5.98 (1H, s, H4), 6.26 (1H, s, H5), 6.66 (1H, s,
H9), 6.73 (1H, s, H10), 7.31–7.39 (5H, m, Ph). 13C NMR
(CDCl3) d 19.8 (CH3), 48.2 (C3,6), 61.2, 61.2 (C1,8), 67.7
(CH2Ph), 128.7, 128.9, 129.0 (C203040 of Ph), 133. 7, 133.9
(C4,5), 136.5 (C10 of Ph), 140.3, 141.5 (C9,10), 115.8
(C13), 145.4 (C12), 151.6 (CO2Bn), 171.5 (carbonyl of
anhydride). IR (KBr, cmꢁ1): 1768 (C]OAnh), 1709
(C]OBn). HRMS C24H21NO5 requires m/z 403.1420,
found 403.1425.
4.1.11. (1a,2b,3b,6b,7b,8a,9b,10b,13b,14b)-15-Benzyl-
oxycarbonyl-15-azahexacyclo[6.6.1.13,6.110,13.02,7.09,14]-
heptadeca-4,11-diene-2,7-dicarboxylic anhydride (18). A
mixture of diacid 13 (114 mg, 0.38 mmol) and cyclopenta-
diene (1.0 g, 15.2 mmol) in acetic anhydride (2.0 g,
19.6 mmol) was stirred at 65 ꢀC overnight. Column chroma-
tography (Et2O/petroleum ether 1:1) afforded the bis-adduct
18 (56 mg, 34%), which crystallized from Et2O/petroleum
ether as colorless crystals, mp 173–174 ꢀC. 1H NMR
(CDCl3) d 1.19 (1H, d, J¼8.4 Hz, Hc), 1.36 (1H, d, J¼
8.4 Hz, Hd), 1.47 (1H, d, J¼10.3 Hz, Ha), 1.56 (1H, d, J¼
10.3 Hz, Hb), 2.41 (1H, d, J¼1.5 Hz, H9), 2.42 (1H, d,
J¼1.5 Hz, H14), 2.88 (1H, s, H10), 2.92 (1H, s, H13),
3.30 (1H, s, H3), 3.35 (1H, s, H6), 4.17 (1H, s, H1), 4.22
(1H, s, H8), 4.99 (1H, d, J¼11.9 Hz, CHaHbPh), 5.06 (1H,
d, J¼11.9 Hz, CHaHbPh), 5.55 (1H, dd, J¼5.6, 3.1 Hz,
H11), 5.87 (1H, dd, J¼5.6, 3.1 Hz, H12), 5.70 (1H, dd,
4.1.14. (1a,2b,3a,6a,7b,8a)-11-Aza-12-oxatetra-
cyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-2,7-dicarboxylic
anhydride (27). Method A. To a solution of anhydride 7b

D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
4345
˚
obtained by FVP of 5b (100 mg, 0.43 mmol) in CDCl3
(0.5 mL) pyrrole was added (160 mg, 2.86 mmol) and kept
at room temperature for 10 min. The reaction mixture was
subjected to radial chromatography (petroleum ether/ethyl
acetate 10:1, then solvent polarity was gradually increased
to ethyl acetate) to afford the product 27, as a colorless solid
a¼22.3696(7), b¼7.4256(2), c¼29.9342(6) A, a¼90, b¼
3
106.724(2), g¼90ꢀ, V¼4762.0(2) A , Z¼8, Dx¼
˚
1.391 Mg mꢁ3
10,869 unique reflections.
,
l¼0.71073 A, T¼150 K, R¼0.027 for
˚
4.2. Supplementary material
1
(17 mg, 16%), mp 168–169 ꢀC. H NMR (CDCl3) d 4.32
(1H, br s, NH), 4.48 (2H, t, J¼1.5 Hz, H1,7), 5.23 (2H, t,
J¼0.8 Hz, H3,6), 6.67 (2H, t, J¼1.5 Hz, H9,10), 6.81 (2H,
t, J¼0.8 Hz, H4,5). 13C NMR (CDCl3) d 63.5 (C2,7), 71.9
(C1,8), 81.2 (C3,6), 138.2, 142.2, 164.9 (CO). IR (KBr,
cmꢁ1): 1778 (C]O). HRMS C12H9NO5 requires m/z
247.0481, found 247.0492.
Full crystallographic data for compounds 9c, 9f, 18, and 19
have been deposited with the Cambridge Crystallographic
Data Centre, deposition numbers CCDC 624019—624022.
These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
Method B. To a solution of anhydride 7b obtained by FVP of
5b (68 mg, 0.29 mmol) in CDCl3 (0.5 mL) N-TMS
substituted pyrrole 22 was added (152 mg, 1.10 mmol) and
kept at room temperature for 30 min. The reaction mixture
was subjected to radial chromatography (petroleum ether/
ethyl acetate 10:1, then solvent polarity was gradually in-
creased to ethyl acetate) to afford 27 (23 mg, 22%).
Acknowledgements
We thank Dr. Alan Lough (University of Toronto) for con-
ducting the X-ray structure analysis and Mr. Max Cryle
(CMA undergraduate vacation scholar), for experimental
help in the preparation of adducts 5f and 9f. The authors
are grateful for funding support provided by the Central
Queensland RDI program.
Method C. To a solution of anhydride 7b obtained by FVP of
5b (76 mg, 0.33 mmol) in CDCl3 (0.5 mL) N-i-Pr3Si pyrrole
23 was added (268 mg, 1.20 mmol) and kept at room tem-
perature for 30 min. The reaction mixture was subjected to
radial chromatography (petroleum ether/ethyl acetate 10:1,
then solvent polarity was gradually increased to ethyl ace-
tate) to afford 27 (14 mg, 13%).
References and notes
1. Kiselev, V. D.; Iskhakova, G. G.; Shtyrlin, Yu. G.; Konovalov,
A. I. Zh. Org. Khim. 1993, 29, 1111; Sauer, J.; Schroeder, B.;
Mielert, A. Chem. Ber. 1967, 100, 315; Sauer, J.; Schroeder,
B.; Wiemer, R. Tetrahedron Lett. 1967, 9, 306.
2. Morita, S.; Fukushima, S.; Kanematsu, K. Tetrahedron Lett.
1979, 20, 2151.
3. Edman, J. R.; Simmons, H. E. J. Org. Chem. 1968, 35, 3808.
4. Bartlett, P. D.; Combs, G. L., Jr.; Le, A.-K. T.; Watson, W. H.;
Galloy, J.; Kimura, M. J. Am. Chem. Soc. 1982, 104, 3131;
Bartlett, P. D.; Blakeney, A. J.; Watson, W. H.; Kimura, M.
J. Am. Chem. Soc. 1980, 102, 1383.
ꢀ
5. Butler, D. N.; Margetic, D.; O’Neill, P. J. C.; Warrener, R. N.
Synlett 2000, 98.
6. Warrener, R. N. Eur. J. Org. Chem. 2000, 3363.
7. RHF/6–31*G//B3LYP/6-31G* FMO-furan gaps of 1–4 and
TCNE are: 11.89, 10.63, 9.46, 9.10, and 10.16 eV, respec-
tively, indicating that 4 is the most reactive dienophile, while
corresponding activation energies for furan addition are 6.65,
14.28, 22.17, 12.09, and 18.99 kcal molꢁ1, indicating that 1 is
the most reactive. High reactivity of 4 could be explained as
a combination of p-bond pyramidalization, ring strain and
4.1.15. (1a,2b,3a,6a,7b,8a)-11-(Triphenylmethyl)-11-
aza-12-oxatetracyclo[6.2.1.13,6.02,7]dodeca-4,9-diene-
2,7-dicarboxylic anhydride (28). To a solution of anhy-
dride 7b obtained by FVP of 5b (100 mg, 0.43 mmol) in
CDCl3 (0.5 mL) N-Tr-pyrrole 24 was added (390 mg,
1.17 mmol) and kept at room temperature for 10 min. The
reaction mixture was subjected to radial chromatography
(petroleum ether/ethyl acetate 10:1, then solvent polarity
was gradually increased to ethyl acetate) to afford the prod-
uct 28, as a colorless solid (25 mg, 12%), mp 192–193 ꢀC.
1H NMR (CDCl3) d 4.79 (2H, t, J¼0.9 Hz, H1,8), 5.29
(2H, t, J¼0.9 Hz, H3,6), 6.56 (2H, t, J¼0.9 Hz, H9,10),
6.74 (2H, t, J¼0.9 Hz, H4,5), 7.01–7.28 (15H, m, Ph). 13C
NMR (CDCl3) d 64.2 (C2,7), 70.8 (C1,8), 80.4 (C3,6),
136.7, 140.1, 144.2, 146.8, 150.2, 152.7, 165.1 (CO). IR
(KBr, cmꢁ1): 1772 (C]O). HRMS C31H23NO5 requires
m/z 489.1576, found 489.1551.
4.1.16. X-ray data: compound 9f. C23H22O4; monoclinic,
space group P2(1)/n, a¼10.2110(8), b¼15.985(2),
ꢀ
stereoelectronic effects (Margetic, D.; Warrener, R. N.;
c¼10.6753(13) A, a¼90, b¼91.034(6), g¼90ꢀ, V¼
Butler, D. N. Sixth Electronic Computational Chemistry
Conference (ECCC-6), paper 39, Homeier, H. H. Ed.,
November 1–30, 1999. http://www.chemie.uni-regens-
burg.de/ECCC6/).
˚
1742.2(4) A , Z¼4, Dx¼1.382 Mg mꢁ3
,
l¼0.71073 A,
3
˚
˚
T¼100 K, R¼0.059 for 3299 unique reflections; 9c:
(C20H15NO6); monoclinic, space group P2(1)/c, a¼
˚
ꢀ
8. Margetic, D.; Butler, D. N.; Warrener, R. N. ARKIVOC 2002,
6, 234.
7.0114(3), b¼16.4247(5), c¼14.0029(7) A, a¼90, b¼
3
101.756(2), g¼90ꢀ, V¼1578.75(11) A , Z¼4, Dx¼
˚
1.537 Mg mꢁ3, l¼0.71073 A, T¼100 K, R¼0.059 for 3592
9. Wiersum, U. E. Recl. Trav. Chim. Pays-Bas 1982, 101, 317.
10. Diels, O.; Alder, K. Liebigs Ann. Chem. 1931, 490, 243; Ripoll,
J. L.; Rouessac, A.; Rouessac, F. Tetrahedron 1978, 34, 19;
Warrener, R. N.; Wang, J.-M.; Weerasuria, K. D. V.; Russell,
R. A. Tetrahedron Lett. 1990, 31, 7069; Roth, W. R.;
Humbert, M.; Wegener, G.; Erker, G.; Exner, H.-D. Chem.
Ber. 1975, 108, 1655.
˚
unique reflections; 18: (C26H23NO5); triclinic, space group
˚
P-1, a¼10.2470(3), b¼11.0605(4), c¼11.4148(5) A, a¼
104.893(2),
b¼103.557(2),
g¼116.008(2)ꢀ,
V¼
3
1030.01(7) A , Z¼2, Dx¼1.385 Mg mꢁ3
,
l¼0.71073 A,
˚
˚
T¼100 K, R¼0.059 for 3592 unique reflections; 19:
(C28H22N2O7); monoclinic, space group P2(1)/n,

4346
D. Margeticꢀ et al. / Tetrahedron 63 (2007) 4338–4346
11. Independently prepared by base hydrolysis of the correspond-
ing diester (Prinzbach, H.; Rivier, J. Helv. Chim. Acta 1970, 53,
2201) and cyclised with acetic anhydride.
16. Williams, R. V.; Sung, C.-L. A.; Kurtz, H. A.; Harris, T. M.
Tetrahedron Lett. 1988, 29, 19.
ꢀ
17. Margetic, D.; Johnston, M. R.; Warrener, R. N.; Butler, D. N.
12. This exo-stereochemical assignment is based on the chemical
shift of the vinylic protons (d 6.58), which is similar to those
observed for the corresponding vinylic protons in other cyclic
diene adducts. Initial attack from the endo-face would form
adduct, which positions the vinylic protons proximate to each
other would result in a significant upfield shift.
Article 37, The Fifth International Electronic Conference on
Synthetic Organic Chemistry (ECSOC-5); Kappe, O.,
Merino, P., Marzinzik, A., Wennemers, H., Wirth, T., Vanden
Eynde, J.-J., Lin, S.-K., Eds.; MDPI: Basel, Switzerland,
2001. ISBN 3-906980-06-5, http://www.mdpi.org/ecsoc-5.htm,
September 1–30, 2001; CD-ROM edition.
13. Prepared by addition of dimethyl acetylenedicarboxylate to
adamantylidenefulvene (Russell, R. A.; Longmore, R.;
Warrener, R. N. J. Chem. Educ. 1992, 69, 164), followed by
base hydrolysis.
14. The molecular plots were produced by the ORTEP-3 v. 1.076
program for Windows, Farrugia, L. J. J. Appl. Crystallogr.
1997, 30, 565.
18. Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179.
19. We find that conducting the FVP at higher pressures also
increases the proportion of secondary fragmentation, a factor
we attribute to increased residence time of the initially formed
norbornadiene anhydride in the pyrolysis tube.
20. Kallos, J.; Deslongchamps, P. Can. J. Chem. 1966, 44, 1239.
21. Warrener, R. N.; Wang, S.; Russell, R. A. Tetrahedron 1997,
53, 3975.
ꢀ
15. Margetic, D.; Warrener, R. N. Croat. Chem. Acta 2003, 76, 357.