2,3,4-Triphenyl-3-azabicyclo[3.2.0]hepta-1,4-diene - Facile ring-opening by electrophiles and novel reactions with dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1002/ejoc.200400433

A 3-azabicyclo[3.2.0]hepta-1,4-diene with no substituent in the cyclobutene moiety has been prepared for the first time; it undergoes extremely facile electrophilic attack at the β-position to give the ring-opened product, probably by a retro-Friedel-Crafts process. The title compound also undergoes a novel reaction with dimethyl acetylenedicarboxylate to afford the azepine. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400433

FULL PAPER
2,3,4-Triphenyl-3-azabicyclo[3.2.0]hepta-1,4-diene ؊ Facile Ring-Opening by
Electrophiles and Novel Reactions with Dimethyl Acetylenedicarboxylate[‡]
Kiyoshi Matsumoto,*[a] Sadahito Goto,[b] Naoto Hayashi,*[c] Hirokazu Iida,[a]
Takane Uchida,[d] and Akikazu Kakehi[e]
Keywords: Azepine / retro-FriedelϪCrafts reaction / Ring opening / Small ring system
A 3-azabicyclo[3.2.0]hepta-1,4-diene with no substituent in
the cyclobutene moiety has been prepared for the first time;
it undergoes extremely facile electrophilic attack at the β-
position to give the ring-opened product, probably by a retro-
Friedel−Crafts process. The title compound also undergoes a
novel reaction with dimethyl acetylenedicarboxylate to
afford the azepine.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
Results and Discussion
The 1,3-dipolar cycloaddition between cis-1,2,3-tri-
phenylaziridine (cis-1a) and dimethylcyclobutene-1,2-dicar-
boxylate (2) took place smoothly and stereospecifically to
produce the corresponding adduct 3a,[6] which was hydro-
lysed as described before[7] to give trans-2,3,4-triphenyl-3-
azabicyclo[3.2.0]heptane-1,5-dicarboxylic acid (trans-4a) in
69% yield. Hydrolysis was carried out with potassium hy-
droxide either in aqueous methanol or in aqueous dimethyl
sulfoxide (Table 1). The latter conditions,[7] which have been
reported to be effective for hydrolysis of sterically hindered
esters, proved to give better results for 3a. The trans-4a was
successfully subjected to oxidative decarboxylation with
lead tetraacetate,[8] affording the desired compound, 2,3,4-
Benzocyclobutene and related compounds, including
their heteroanalogues, represent a unique compromise be-
tween the thermodynamic stability associated with an aro-
matic system and the kinetic reactivity of a strained cyclo-
butene.[1,2]
Although 3-thiabicyclo[3.2.0]hepta-1,4-diene and its
derivatives are relatively well known,[3,4] the sole example
of the corresponding aza-analogue was reported by Garratt
et al., who synthesised 6,7-di-tert-butyl-3-thiabicyclo-
[3.2.0]hepta-1,4-diene and its pyrrole and furan analogues
through the base-catalysed rearrangement of the corre-
sponding 4-heterohepta-1,6-diynes.[5] We now report the
first synthesis of the title compound with no substituent in
the cyclobutene moiety along with the extremely facile ring-
opening of 5a by electrophiles and novel reactions of the
title compound with dimethyl acetylenedicarboxylate
(DMAD).
triphenyl-3-azabicyclo[3.2.0]hepta-1,4-diene
(5a),
in
50Ϫ60% yields. In our hands, however, this method was not
amenable to production of the similar adducts 3b or 3c,[6]
from aziridines such as 1-benzyl-2,3-diphenyl-aziridine (1b)
and 1-cyclohexyl-2-aroyl-aziridines (1c). No dicarboxylic
acid 4c was obtained under the above conditions, for ex-
ample, and neither did cis- or trans-4b smoothly undergo
decarboxylation (Scheme 1). Furthermore, all attempts to
[‡]
This work was in part performed at Graduate School of Human
and Environmental Studies, Kyoto University, Kyoto 606-8501.
[a]
Faculty of Pharmaceutical Sciences, Chiba Institute of Science, decarboxylate cis- and trans-4b were unsuccessful under
Choshi, Chiba 288-0025 Japan
Fax: (internat.) ϩ 81-479-30-4501
conditions either similar to those above or even more for-
ced, presumably due to preferential attack at the benzylic
E-mail: kmatsumoto@cis.ac.jp
Research Center, Toyobo Co., LTD,
Otsu 520-0292, Japan
[b]
[c]
[d]
[e]
position[9] (Table 2).
Compound 5a has an m.p. of 218Ϫ219 °C and is stable
at room temperature. The methylene protons and carbons
Faculty of Science, Toyama University,
Toyama 930-8555, Japan
1
are observed at δ ϭ 3.41 (s, H NMR) and δ ϭ 27.50 (13C
Faculty of Education, University of Fukui,
Fukui 910-0017, Japan
Faculty of Engineering, Shinshu University,
Nagano 380-8533, Japan
NMR), and the coupling constant (J) in the cyclobutene
moiety is 140 Hz. This value is comparable to those of
Eur. J. Org. Chem. 2004, 4667Ϫ4671
DOI: 10.1002/ejoc.200400433
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K. Matsumoto, S. Goto, N. Hayashi, H. Iida, T. Uchida, A. Kakehi
FULL PAPER
Table 1. Hydrolysis of diesters 3aϪ3c
Entry
Diester
3
Method
Time (h)
4
4
R1
R2
R3
H
Yield (%)[a]
m.p. (°C)
1
2
3
4
5
6
7
8
trans-3a
trans-3a
trans-3b
trans-3b
cis-3b
cis-3b
trans-3c
trans-3c
Ph
Ph
A
B
A
B
A
B
A
B
60
35
138
17
29
49
69
95
63
69
0
65
0
221.5Ϫ224.0
220.0Ϫ221.8
Bn
Ph
H
Bn
H
Ph
H
239.3Ϫ243.0
C6H11
COPh
65
37
0
[a]
Isolated yields.
Scheme 1. Synthesis of 5a and ring-opening by electrophiles
Table 2. Oxidative decarboxylation of diacids 4 with Pb(OAc)4
Table 3. Treatment of 2,3,4-triphenyl-3-azabicyclo[3.2.0]hepta-1,4-
diene (5a) with electrophiles
Entry Diacids
4
Temp. (°C) Time 5a
R1 R2 R3
(h)
Yield (%)[a]
Entry
YϪX
Temp (°C)
Time
6 Yield (%)[a]
1
2
3
4
trans-4a Ph Ph
trans-4a
H
room temp.
70
70
3
3
72
5
46
55
0
1[b]
2[b]
3[b]
4[c]
5[d]
6[e]
HϪONO2
HϪCl
HϪOAc
HϪOCH3
HϪOCH3
BrϪBr
room temp.
room temp.
room temp.
reflux
room temp.
room temp.
a few min
2.5 h
76 h
14 d
16 h
(6a) quant.
(6b) quant.
(6c) 73
trans-4b Bn Ph
H
Ph 70
cis-4b
Bn
H
0
(6d) 36
(6d) quant.
(9) quant.
[a]
Isolated yield.
a few min
[a] Isolated yields. [b] A suitable amount of 1  aqueous HX solution
the parent cyclobutene (140 Hz),[10] benzocyclobutene
(138 Hz)[11] and the heteroanalogues (137Ϫ140 Hz).[3c]
crystal structure of this compound would thus be interest-
ing, but unfortunately all attempts to obtain a crystal suit- are summarized in Table 3. The reaction can readily be ex-
able for X-ray measurement failed in our hands. plained in terms of an initial electrophilic addition of a pro-
[d]
in benzene was used.[c] HX was used as solvent.
amount of 1  HNO3 was used. In chloroform.
A catalytic
[e]
A
During the workup after decarboxylation of trans-2,3,4- ton to form a nitrogen-stabilized carbocation, which un-
triphenyl-3-azabicyclo[3.2.0]heptane-1,5-dicarboxylic acid dergoes nucleophilic attack at the γ-position, giving the
(4a), we found an extremely facile ring-opening of 5a by product 6. The reaction can formally be regarded as a retro-
electrophiles in the cyclobutene moiety. Thus, treatment of FriedelϪCrafts reaction. The driving force of the reaction
5a with 1  nitric acid in benzene at room temperature af- must be not only strain of the cyclobutene ring but also the
forded the corresponding ester 6a in quantitative yield. stabilization of the carbocation by the nitrogen atom and
Such conversion took place even in methanol, albeit after the phenyl groups. The higher strain in 7 relative to 8 is
2 weeks at reflux and in only moderate yield. The results apparent from the number of sp2-hybridised carbon atoms
4668
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Eur. J. Org. Chem. 2004, 4667Ϫ4671

2,3,4-Triphenyl-3-azabicyclo[3.2.0]hepta-1,4-diene
FULL PAPER
Scheme 2. Mechanism of ring-opening of 5a by electrophiles
in the four-membered ring (i.e., two such atoms in 7 and Treatment of 5a with 1 equiv. of DMAD in 1,2-dichloro-
only one in 8), together with i-strain. Although pyrroles benzene at reflux for 3 h afforded a 1:1 adduct as orange
1
usually undergo electrophilic attack at their α-positions, this needles in 54% yield. Inspection of the H and 13C NMR
was not the case here, attack taking place at the β-position, spectra confirmed that the compound had retained its
probably because of the unfavourable resonance structure cyclobutene ring, but that it was unsymmetrically substi-
(strained cyclobutene) derived from electrophilic attack at tuted. An X-ray analysis of this compound established that
the α-position. Indeed, from semiempirical molecular or- the compound had the structure 13, which is also consistent
bital calculations, the heat of formation of 7 is higher than with the NMR spectroscopic data. Photochemical[13a] and
that of 8.[12] In a similar fashion, 5a readily reacted with thermal[13b] formation of analogous but isomeric azepine
bromine to give 9, whereas the parent 3-thiabicyclo- diesters had been reported from pyrrole and DMAD, and
[3.2.0]hepta-1,4-diene 10 was reported to react with bro- from 3-azaquadricyclane. No thermal formation of an
mine to afford the tetrabromide 11 (Scheme 3).[3b]
azepine from pyrroles has been reported,[14,15] although
Treatment with DMAD was next performed, since we treatment of 1-methylindole with DMAD gave the azep-
hoped the compound 5a would serve either as a diene or ine.[16] The formation of 13 can be explained in terms of an
an azomethine ylide or as both, as shown in structure 12. initial DielsϪAlder reaction between 5a and DMAD to
Scheme 3. Reaction of bromine with 5a compared with 10
Scheme 4. Plausible mechanism for the formation of the azepine 13 on treatment of 5a with DMAD
Eur. J. Org. Chem. 2004, 4667Ϫ4671
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K. Matsumoto, S. Goto, N. Hayashi, H. Iida, T. Uchida, A. Kakehi
FULL PAPER
128.1,129.1, 138.7, 139.1, 145.7, 172.3, 173.8 ppm. C26H23NO4
(413.5): calcd. C 75.53, H 5.61, N 3.39; found C 75.31, H 5.46,
N 3.35.
give the adduct 14, which undergoes an intramolecular nu-
cleophilic attack to form the zwitterionic intermediate 15,
followed by rearrangement. The driving force for this intra-
molecular nucleophilic attack and subsequent novel re-
arrangement might be the highly sterically congested nature
of the initial adduct.[17] As a passing note, we initially pro-
posed intervention of a bicyclic aziridine 16 from 15, but
16 would also be highly energetically (i.e., sterically) un-
favourable according to semiempirical molecular orbital
calculations.[17] The calculated values of the kinetic energies
of the transition states should in principle be more import-
ant, but unfortunately it was not possible, in our hands, to
find reasonable transition state structures by the AM1 and
PM3 methods (Scheme 4).
trans-3-Benzyl-2,4-diphenyl-3-azabicyclo[3.2.0]heptane-1,5-di-
carboxylic Acid (trans-4b): M.p. 220Ϫ222 °C. 1H NMR (270 MHz,
CDCl3): δ ϭ 1.95Ϫ2.60 (4 H), 2.72, 3.70 (dd, J ϭ 15.7 Hz, 2 H),
4.23 (s, 1 H), 5.14 (s, 1 H), 7.23Ϫ7.94 (m, 15 H) ppm. 13C NMR
(67.8 MHz, [D6]DMSO): δ ϭ 18.1, 28.3, 50.1, 56.4, 59.8, 70.5, 71.7,
126.7, 127.3, 127.4, 127.6, 127.9, 128.4, 137.0, 137.5, 138.7, 172.6,
173.5 ppm. C27H25NO4 (427.5): calcd. C 75.86, H 5.89, N 3.28;
found C 75.56, H 6.02, N 3.25.
cis-3-Benzyl-2,4-diphenyl-3-azabicyclo[3.2.0]heptane-1,5-dicarb-
oxylic Acid (cis-4b): M.p. 239Ϫ243 °C. 1H NMR (270 MHz,
CDCl3): δ ϭ 1.95Ϫ2.60 (m, 4 H), 2.72, 3.70 (dd, J ϭ 15.7 Hz, 2
H), 4.23 (s, 1 H), 5.14 (s, 1 H), 7.23Ϫ7.94 (m, 15 H) ppm. 13C
NMR (67.8 MHz, [D6]DMSO): δ ϭ 18.1, 28.9, 50.1, 56.4, 59.8,
70.5, 71.7, 126.7, 127.3, 127.4, 127.6, 127.9, 128.4, 137.0, 137.5,
138.7, 172.6, 173.5 ppm. C27H25NO4 (427.5): calcd. C 75.86, H
5.89, N 3.28; found C 75.56, H 6.02, N 3.25.
Conclusion
In conclusion, since a wide variety of mesoionic com-
pounds[18] and non-stabilized azomethine ylides[19] are
available, it may be anticipated that this strategy might pro-
vide a route to 3-azabicyclo[3.2.0]hepta-1,4-diene systems,
which may in turn serve as useful building blocks in or-
ganic synthesis.
Preparation of 2,3,4-Triphenyl-3-azabicyclo[3.2.0]hepta-1,4-diene
(5a): Lead tetraacetate (0.123 g, 0.250 mmol) was added portion-
wise under argon, with stirring, to a solution of trans-2,3,4-tri-
phenyl-3-azabicyclo[3.2.0]heptane-1,5-dicarboxylic acid (0.050 g,
0.121 mmol) in dry pyridine (2 mL). The mixture was heated to 70
°C for 3 h. After evaporation of the solvent under vacuum, the
residue was chromatographed on alumina, eluting with benzene,
giving 5a as white powder in 55% yield (0.021 g, 0.066 mmol). M.p.
Experimental Section
Melting points were taken on a Yanagimoto micro melting point
apparatus and were uncorrected. The 1H NMR spectra were meas-
ured either on a JEOL JNM-EX270 (270 MHz) or on a JNM-
ALPHA500 (500 MHz) instrument. The 13C NMR spectra were
recorded either on a JNM-EX270 or on a JNM-ALPHA500 pulsed
Fourier-transform spectrometer, operating at 67.80 Hz or at
125.65 Hz, respectively. Chemical shifts are expressed in parts per
million downfield from internal tetramethylsilane. Either partial
proton decoupling or the DEPT method was used to distinguish
between individual carbon atoms. Preparative medium-pressure
liquid chromatography was carried out on a column (25 ϫ 310 mm)
prepacked with silica gel (Lobar, LiChroprep Si60, Merck).
1
218.0Ϫ219.0 °C. H NMR (270 MHz, CDCl3): δ ϭ 3.41 (s, 4 H),
6.92Ϫ7.32 (m, 15 H) ppm. 13C NMR (68 MHz. CDCl3): δ ϭ 27.50,
125.45, 126.42, 127.78, 127.92, 128.92, 129.55, 132.54, 140.22 ppm.
C24H19N (321.4): calcd. C 89.68, H 5.96, N 4.36; found C 89.65,
H 5.87, N 4.33.
Reactions between 5a and Electrophiles
With Nitric Acid: Nitric acid (1 , 0.1 mL) was added with stirring,
at room temp., to a solution of 5a (0.13 mmol) in dichloromethane
(1 mL) for a few min. After evaporation of solvent, pure 2-(1Ј, 2Ј,
5Ј-triphenyl-3Ј-pyrrolyl)ethyl nitrate (6a) was obtained in quantitat-
1
ive yield. M.p. 156.7Ϫ157.1 °C. H NMR (270 MHz, CDCl3): δ ϭ
Dimethyl 3-azabicyclo[3.2.0]heptane-1,5-dicarboxylates 3 were pre-
2.94 (t, J ϭ 7.3 Hz 2 H), 4.61 (t, J ϭ 7.3 Hz 2 H), 6.42 (s, 1 H),
6.43Ϫ7.23 (m, 15 H) ppm. 13C NMR (67.8 MHz, CDCl3): δ ϭ
24.23, 73.59, 110.03, 116.50, 126.29, 126.93, 127.10, 127.92, 128.43,
128.50, 128.73, 130.76, 131.95, 132.81, 133.71, 134.46, 138.74 ppm.
C24H20N2O3 (384.4): calcd. C 74.98, H 5.24, N 7.28; found C 74.98,
H 5.16, N 7.24. MS (m/z): 384 [Mϩ].
viously reported in our paper.[6]
General Procedure for Hydrolysis of Dimethyl 3-Azabicy-
clo[3.2.0]heptane-1,5-dicarboxylates (3). Method A: A mixture of 3
(2.3 mmol), potassium hydroxide (9.00 mmol, 0.60 g), methanol
(15 mL) and water (8 mL) was heated at reflux for 60 h. After the
system had cooled, water (6 mL) was added to the solution, which
was made acidic with 6  sulfuric acid. The colourless precipitates
were filtered and dried in vacuo, to give almost pure 4.
With Hydrogen Chloride: Hydrogen chloride (1 , 0.1 mL) was ad-
ded at room temp. with stirring to a solution of 5a (50 mg,
0.13 mmol) in dichloromethane (1 mL). After evaporation of sol-
vent in vacuo, pure 2-(1Ј,2Ј,5Ј-triphenyl-3Ј-pyrrolyl)ethyl chloride
(6b) was obtained in quantitative yield as a colourless powder. M.p.
145.2Ϫ147.8 °C. 1H NMR (270 MHz, CDCl3): δ ϭ 3.00 (t, J ϭ
7.6 Hz, 2 H), 3.69 (t, J ϭ 7.6 Hz 2 H), 6.43 (s, 1 H), 6.90Ϫ7.23 (m,
15 H) ppm. 13C NMR (67.8 MHz, CDCl3): δ ϭ 30.26, 44.93,
110.05, 118.85, 126.16, 126.85, 126.92, 127.84, 127.91, 128.39,
128.46, 128.72, 130.73, 132.11, 132.90, 133.41, 134.18, 138.78 ppm.
C24H20ClN (357.9): calcd. C 80.55, H 5.63, N 3.91; found C 80.26,
H 5.40, N 3.93.
Method B: A mixture of 3 (0.29 mmol), potassium hydroxide
(1.22 mmol, 0.076 g), DMSO (20 mL) and water (2 mL) was kept
at 80 °C in an oil bath for 17 h. The cooled solution was poured
into water (500 mL), acidified with 6  sulfuric acid and extracted
with diethyl ether. The organic layer was dried with anhydrous
MgSO4. After evaporation of solvent, the residue was recrystallised
from diethyl ether/hexane to give 4 as colourless crystals.
trans-2,3,4-Triphenyl-3-azabicyclo[3.2.0]heptane-1,5-dicarboxylic
Acid (trans-4a): M.p. 222Ϫ224 °C. 1H NMR (270 MHz, CDCl3):
δ ϭ 1.55Ϫ2.19 (m, 4 H), 5.47 (s, 1 H), 5.92 (s, 1 H), 6.43Ϫ7.34 (m,
15 H) ppm. 13C NMR (67.8 MHz, [D6]DMSO): δ ϭ 20.0, 28.7,
With Acetic Acid: Acetic acid (0.5 mL) was added with stirring at
room temp to a solution of 5a (23 mg, 0.072 mmol) in dichloro-
58.5, 61.0, 68.3, 74.5, 118.1, 119.4, 126.8, 127.0, 127.2, 127.8, methane (2 mL). After evaporation of solvent under vacuum, pure
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Eur. J. Org. Chem. 2004, 4667Ϫ4671

2,3,4-Triphenyl-3-azabicyclo[3.2.0]hepta-1,4-diene
FULL PAPER
2-(1Ј,2Ј,5Ј-triphenyl-3Ј-pyrrolyl)ethyl acetate (6c) was obtained in
73% yield as a colourless powder. M.p. 165.8Ϫ166.5 °C. H NMR
ture, Japan. The authors are also grateful to the Ministry of Edu-
cation, Culture, Sports, Science, and Technology, Japan for pur-
chasing the high-field NMR instruments (JEOL JNM-A500 and
JNM-EX270) through the special fund to KM (Graduate School
of Human and Environmental Studies, Kyoto University) in 1992.
1
(270 MHz, CDCl3): δ ϭ 2.03 (s, 3 H), 2.86 (t, J ϭ 7.3 Hz, 2 H),
4.27 (t, J ϭ 7.3 Hz, 2 H), 6.43 (1 H, s), 6.92Ϫ7.21 (m, 15 H) ppm.
13
C NMR (67.8 MHz, CDCl3): δ ϭ 21.04, 25.84, 65.27, 110.30,
118.29, 126.11, 126.77, 127.75, 127.87, 128.41, 128.75, 130.80,
132.29, 133.03, 133.39, 134.16, 138.89, 171.09 ppm. C25H21NO2
(367.4): calcd. C 81.72, H 5.76, N 3.81; found C 81.55, H 5.69,
N 3.90.
[1]
Part of this work has previously been published as a communi-
cation; see: K. Matsumoto, S. Goto, N. Hayashi, T. Uchida,
A. Kakehi, J. Chem. Soc., Perkin 1 Commun. 1997, 2691.
[2]
R. P. Thummel, Acc. Chem. Res. 1980, 13, 70; B. Halton,
With Methanol: A solution of 5a (20 mg, 0.062 mmol) in methanol
(2 mL) was heated at reflux for 2 weeks. After evaporation of sol-
vent, the residue was recrystallised from dichloromethane/hexane
to afford 3-(2-methoxyethyl)-1,2,5-triphenylpyrrole (6d) as a white
powder in 36% yield (10 mg, 0.028 mmol). M.p. 165.5Ϫ166.5 °C.
1H NMR (270 MHz, CDCl3): δ ϭ 2.82 (t, J ϭ 7.3 Hz, 2 H), 3.25
(s, 3 H), 3.63 (t, J ϭ 7.3 Hz, 2 H), 6.44 (s, 1 H), 6.91Ϫ7.20 (m, 15
H). 13C NMR (67.8 MHz, CDCl3): δ ϭ 26.72, 58.51, 73.57, 110.35,
119.19, 125.97, 126.58, 126.67, 127.66, 127.82, 128.39, 128.75,
130.78, 132.44, 133.15, 134.02, 138.99. C25H23NO (353.5): calcd. C
84.95, H 6.56, N 3.96; found C 84.84, H 6.42, N 4.03.
Chem. Rev. 1973, 73, 113.
[3] [3a]
P. J. Garratt, K. P. C. Vollhardt, J. Am. Chem. Soc. 1972,
94, 7087. [3b] P. J. Garratt, D. N. Nicolaides, J. Org. Chem. 1974,
[3c]
39, 2222.
40, 970.
P. J. Garratt, S. B. Neoh, J. Org. Chem. 1975,
[4]
[4a] B. E. Ayres, S. W. Longworth, J. F. W. McOmie, Tetrahedron
[4b]
1975, 31, 1755.
K. P. C. Vollhardt, R. G. Bergman, J. Am.
Chem. Soc. 1972, 94, 8950; J. Am. Chem. Soc. 1973, 95, 7538.
[4c]
R. G. Bergman, K. P. C. Vollhardt, J. Chem. Soc., Chem.
[4d]
Commun. 1973, 214.
H. Hauptmann, Tetrahedron Lett.
[4e]
1974, 3589.
M. P. Cava, M. V. Lakshmikantham, M.
Behforouz, J. Org. Chem. 1974, 39, 206. [4f] P. Vogel, M. Hardy,
Helv. Chim. Acta 1974, 57, 196.
When the same reaction was performed at room temp. with a cata-
lytic amount of 1  HNO3, 6d was obtained in quantitative yield
(see Table 3).
[5]
[6]
[7]
[5a] P. J. Garratt, S. B. Neoh, J. Am. Chem. Soc. 1975, 97, 3255.
[5b]
P. J. Garratt, S. B. Neoh, J. Org. Chem. 1979, 44, 2667.
K. Matsumoto, H. Iida, T. Uchida, Y. Yabe, A. Kakehi, J. W.
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K. Matsumoto, Y. Kono, T. Uchida, J. Org. Chem. 1977, 42,
1103.
Treatment of 5a with Bromine: A solution of bromine (0.1 mL) in
chloroform (1 mL) was added dropwise to a stirred solution of 5a
(30 mg, 0.093 mmol) in chloroform (2.5 mL). Evaporation of the
solvent in vacuo gave 2-(1Ј,2Ј,5Ј-triphenyl- 3Ј-pyrrolyl)ethyl acetate
2-(4Ј-bromo-1Ј,2Ј,5Ј-triphenyl-3Ј- pyrrolyl)ethyl bromide as a white
[8]
[9]
R. P. Thummel, J. Chem. Soc., Chem. Commun. 1974, 899.
V. V. Dhekne, A. S. Rao, Synth. Commun. 1978, 8, 135.
[10] [10a]
1
S. Borcic, J. D. Roberts, J. Am. Chem. Soc. 1965, 87, 1056.
powder. M.p. 196.0Ϫ197.0 °C (dec). H NMR (270 MHz, CDCl3):
[10b] E. A. Hill, J. D. Roberts, J. Am. Chen. Soc. 1967, 89, 2047.
δ ϭ 3.11 (t, J ϭ 7.8 Hz, 2 H), 3.54 (t, J ϭ 7.8 Hz, 2 H), 6.84Ϫ7.25
(m, 15 H) ppm. 13C NMR (67.8 MHz, CDCl3): δ ϭ 30.01, 31.57,
99.66, 118.99, 127.04, 127.30, 127.53, 127.75, 128.07, 128.41,
128.61, 130.64, 130.89, 131.41, 132.74, 138.20 ppm. C24H19Br2N
(481.2): calcd. C 59.63, H 4.08, N 2.75; found C 59.90, H 3.98,
N 2.91.
[11] [11a]
G. Fraenkel, Y. Asahi, M. J. Mitchel, M. P. Cava, Tetra-
[11b]
hedron 1964, 20, 1179.
H. Hart, J. A. Hartlarger, R. W.
Fish, R. R. Rafos, J. Org. Chem. 1966, 31, 2244.
[12]
The heats of formation of the carbocations 7 and 8 were ob-
tained by use of the CAChe systems (Version 3.7, CAChe
Scientific, Oxford Molecular Group) AM1: M. J. S. Dewar, E.
G. Zoebisch, E. F. Hearly, J. J. P. Stewart, J. Am. Chem. Soc.
1985, 107, 3902; Heat of formation of cation 7: 331.63 kcal/
mol; heat of formation of cation 8: 311.62 kcal/mol; PM3: J. J.
Stewart, J. Comp. Chem. 1989, 10, 209; Heat of formation of
cation 7: 138.21 kcal/mol; heat of formation of cation 8: 120.12
kcal/mol.
R. P. Gandhi, V. K. Chadha, Indian J. Chem. 1971, 9, 305.
H. Prinzbach, R. Fuchs, R. Kitzing, Angew. Chem. Int.
Ed. Engl. 1968, 7, 67.
R. A. Jones, G. P. Bean, The Chemistry of Pyrroles, Academic
Press, London, 1977, chapter 6.
Treatment of 5a with DMAD: A solution of 5a (0.034 g, 0.11 mmol)
and DMAD (0.12 cm3, 1 mmol,) in 1,2-dichlorobenzene (3 mL)
was heated at reflux under argon for 3 h. After evaporation of sol-
vent, the residue was chromatographed on silica gel with hexane/
ethyl acetate as eluent to give the product, which was recrystallised
from ethanol to produce the azepine 13 as orange needles. M.p.
[13] [13a]
[13b]
258.3Ϫ263.0 °C (dec.). 1Η NMR (270 MHz, CDCl3):
δ ϭ
2.97Ϫ3.41 (m, 4 H), 3.55 (s, 3 H), 3.71 (s, 3 H), 6.75Ϫ7.87 (m, 15
H) ppm. 13C NMR (67.8 MHz, CDCl3): δ ϭ 29.22, 29.47, 52.31,
52.42, 112.71, 119.01, 119.68, 127.64, 128.05, 128.27, 128.39,
128.63, 128.68, 129.18, 132.29, 134.20, 134.63, 135.98, 142.05,
145.23, 146.51, 151.11, 165.25, 167.30 ppm. C30H25NO4 (463.5):
calcd. C 77.74, H 5.44, N 3.02; found C 77.80, H 3.08, N 2.99.
[14]
[15]
[16]
[17]
R. M. Acheson, Adv. Heterocycl. Chem. 1965, 1, 125; R. M.
Acheson, N. F. Elmore, Adv. Heterocycl. Chem. 1978, 23, 263.
R. M. Acheson, J. Bridson, T. S. Cameron, J. Chem. Soc., Per-
kin Trans. 1 1972, 968.
The heats of formation of 13, 14, and 15 were obtained by use
of the CAChe systems (Version 4.1.1, Oxford Molecular
Group) AM1: M. J. S. Dewar, E. G. Zoebisch, E. F. Hearly, J.
J. P. Stewart, J. Am. Chem. Soc. 1985, 107, 3902; 5a: 387.12538,
13: 29.70126, 14: 106.03925, 15: 65.75824, 16: 105.80957 kcal/
mol; PM3: J. J. Stewart, J. Comp. Chem. 1989, 10, 209; 5a:
350.41893, 13: 7.75890, 14, 55.42717, 15, 35.09190, 16:
78.16375 kcal/mol. As pointed out by one of the referees, there
are great differences in the heats of formation of a single inter-
mediate by different methods. These values are not absolute in
nature but only of relative comparison.
Crystal Structure Determination for Compound 13: The results were
already reported in a preliminarily communication.[1] CCDC-
207/142 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; Fax: ϩ44-1223-336-033; E-mail:
deposit@ccdc.cam.ac.uk].
[18]
[19]
W. D. Ollis, S. P. Stanforth, C. A. Ramsden, Tetrahedron 1985,
41, 2295.
O. Tsuge, S. Kanemasa, Adv. Heterocyclic. Chem. 1989, 45, 231.
Received June 21, 2004
Acknowledgments
This work was supported in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports and Cul-
Eur. J. Org. Chem. 2004, 4667Ϫ4671
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4671