Cyclization of electron-deficient cyclopentadienone with 2-alkenyl and 2-alkynylamines via sequential pericyclic reaction pathway

Article abstract of DOI:10.1021/jo015941o

The pericyclic reactions of 2,5-bis(methoxycarbonyl)-3,4-diphenylcyclopentadienone (1a) with both allylic and propargylic amines have been investigated. The reaction proceeded via initial formation of the 1,4 adducts followed by the ene cyclization and/or

Full text of DOI:10.1021/jo015941o

8902
J . Org. Chem. 2001, 66, 8902-8911
Cycliza tion of Electr on -Deficien t Cyclop en ta d ien on e w ith
2-Alk en yl a n d 2-Alk yn yla m in es via Sequ en tia l P er icyclic Rea ction
P a th w a y
Yasuyuki Yoshitake, Kouki Yamaguchi, Chika Kai, Takayo Akiyama, Chiaki Handa,
Tamaki J ikyo, and Kazunobu Harano*
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi,
Kumamoto 862-0973, J apan
harano@gpo.kumamoto-u.ac.jp
Received J uly 18, 2001
The pericyclic reactions of 2,5-bis(methoxycarbonyl)-3,4-diphenylcyclopentadienone (1a ) with both
allylic and propargylic amines have been investigated. The reaction proceeded via initial formation
of the 1,4 adducts followed by the ene cyclization and/or sequential pericyclic reactions depending
upon the structures of the amines. The reaction of 1a with diallylamine (2a ) gave the tetracyclic
compound (3a ). On the other hand, the reaction of 1a with 2-propynylamine (2c) gave exclusively
the bicyclic compound (5c). In the reactions with the secondary 2-propynylamines (2d ,e), the
tetracyclic compounds (3d ,e) were exclusively formed. The reactions of 1a with R-branched primary
1,1-dialkyl-2-propynylamines (2f,g) gave mixtures of 3- and 5-type compounds. The tetracyclic
compounds 3 were formed from the intramolecular [4+2]π cycloadditions of the [1,5]-sigmatropic
rearrangement products of the 1,4 adducts of 1a and 2, followed by the [1,5]-sigmatropic
rearrangement of hydrogen and dehydrogenation. The bicyclic compounds 5 were derived from the
[2π+2π+2σ] reaction of the 1,4 adducts of 1a and 2. The one-pot multistage sequential pericyclic
reactions were discussed on the basis of the X-ray crystallographic structures and the MO calculation
data.
In tr od u ction
[1,6-ab]naphthalen-2-one derivative (3a ) as a one-pot
reaction product, without knowing its formation mech-
anism.
On the basis of these backgrounds, we considered that
a marked difference in the reaction behavior between the
hydroxy- and amino-substituted alkenes depends on the
characters of their HOMO and the novel tetracyclic
compound 3a is presumably derived from the 1,4 adduct
of 1a and 2a .
Cyclopentadienones (1) are antiaromatic diene com-
ponents1 having very low lowest unoccupied molecular
orbital (LUMO) energy levels. However, there are not
many cyclopentadienones existing as monomers. Of
those, 2,5-bis(methoxycarbonyl)-3,4-diphenylcyclopenta-
dienone (1a ), which exists as a monomer, is a powerful
4π source, and a systematic study of the pericyclic
reactions of 1a with various unsaturated compounds was
made by Kanematsu and associates.2 On the other hand,
it is well-known that 1a also shows high reactivity toward
alcohols or amines to give the 1,4 adducts.3 The precon-
ception about the priority of 1,4 addition over cycload-
dition seems to prevent the detailed study of the cycload-
dition reaction of 1a with unsaturated compounds bearing
a hydroxy or an amino group.
We now discuss the reactions in detail, with newly
obtained data, to clarify the overall character of the
cyclization reactions of 1a with unsaturated amines.
Resu lts a n d Discu ssion
Th eor etica l Con sid er a tion of th e Rea ction Be-
h a vior of Cyclop en ta d ien on es (1a ) tow a r d Dia llyl-
a m in es (2a ). To know the reaction behavior of 1a , the
MNDO-PM35 calculations were carried out. The frontier
molecular orbital (FMO) energy levels and coefficients
of 1a and 2a are graphically represented in Figure 1,
which involves the FMO of allyl alcohol. As can be seen
in Figure 1, the interaction between the LUMO of 1a and
the HOMOs of the olefins plays a leading role in the
reactions.
The HOMO of diallylamine (2a ) is localized at the lone
pair of the nitrogen atom (n-HOMO), and the dienophilic
π-orbital is found in the NHOMO, whereas the HOMO
of allyl alcohol is π-HOMO. This implies that allylic
During the course of a study on the pericyclic reaction
behavior of cyclopentadienones, we found that 1a reacted
with allylic alcohols to give the [4+2]π cycloadduct.4 On
the other hand, in the reaction with diallylamine (2a ),
we isolated the 2a,3,4,4a,5,9c-hexahydro-3-aza-pentaleno-
* Corresponding author.
(1) Inagaki, S.; Hirabayashi, Y. J . Am. Chem. Soc. 1977, 99, 7418-
7423.
(2) Harano, K.; Yasuda, M.; Ban, T.; Kanematsu, K. J . Org. Chem.
1980, 45, 4455-4462. Mori, M.; Hayamizu, A.; Kanematsu, K. J . Chem.
Soc., Perkin Trans. 1 1981, 1259-1272. J ikyo, T.; Eto, M.; Harano, K.
J . Chem. Soc., Perkin Trans. 1 1998, 3463-3470 and references
therein.
(3) Eistert, B.; Thommen, A. J . Chem. Ber. 1971, 104, 3048; Arackal,
T. J .; Eistert, B. Chem. Ber. 1973, 106, 3788.
(4) (a) Harano, K.; Eto, M.; Oya, T.; Nakamoto, S.; Hisano, T.
Tetrahedron Lett. 1992, 43, 6473-6476. The atomic coordinates for
the nonhydrogen atoms of 3a were communicated. (b) Eto, M.; Harano,
K.; Oya, T.; Hisano, T. Chem. Pharm. Bull. 1993, 41, 97-107.
(5) PM3 calculations were performed using MOPAC ver. 6.0 (QCPE
No. 445) and MOPAC97. Stewart J . J . P. QCPE Bull., 1990, 10, 86.
MOPAC97, Fujitsu Ltd: Tokyo, J apan, 1998.
10.1021/jo015941o CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/27/2001

Cyclization of Cyclopentadienone with Alkynylamine
J . Org. Chem., Vol. 66, No. 26, 2001 8903
F igu r e 1. FMO coefficients and energy levels.
Sch em e 1
alcohols undergo [4+2]π cycloaddition and allylic amines
undergo 1,4 addition.
Rea ction of 1a w ith 2-P r op en yla m in es (2a ,b). A
mixture of 1a and 2a in DMF was allowed to stand at
room temperature until 1a could not be recognized on
the thin-layer chromatogram (TLC) of the reaction
mixture. Purification of the crude product by chroma-
tography on silica gel with n-hexane-benzene elution
afforded three products (3a , 4a , and 1z). The mass
spectrum of 3a showed a dehydrogenated 1:1 adduct of
1a and 2a . The IR spectrum showed a conjugated
carbonyl absorption band at 1706 cm-1, and UV-vis
absorption spectrum showed an n-π* absorption, indi-
cating the presence of the 2-methoxycarbonyl-3-phenyl-
1
cyclopentenone moiety. The H NMR spectrum exhibited
that the three olefinic hydrogens of an N-allyl group
changed to the hydrogens on sp3 carbons. The 13C NMR
spectra supported this assignment. The 1H detected
heteronuclear multiple bond connectivity (HMBC) spec-
trum and numbers of aromatic protons (9H) suggested
that the terminal carbon of an allyl group connected with
the 2-position of a phenyl group. The methyl protons of
a methoxycarbonyl group showed high-field shift [δ 3.02
for C(2a)-CO2Me] compared with the other methyl group
[δ 3.89 for C(1)-CO2Me], implying that the ester and the
9C-phenyl groups are in a nearly face-to-face disposition.
To clarify the full structure of 3a , a single-crystal X-ray
analysis was performed. Compound 3a has isoindole
skeleton condensed with benzene and cyclopentenone
rings, which is assumed to be formed from intramolecular
cycloaddition of the aromatic diene (styrene moiety) with
the allyl group (Figure S1).
Compound 4a has molecular formula of C27H27NO6,
which corresponds to 1a + 2a + oxygen. The IR and UV
spectra are similar to those of 3a . The IR spectrum
exhibited hydroxy and enone absorption bands. The latter
was confirmed by the vis absorption spectral data. The
NMR spectral data showed adjacent three sp3 carbons.
The HMBC spectrum showed correlation between 3-H
and 4-C, implying the formation of a pyrrolidine ring
condensed with the cyclopentenone moiety (2,3,3a,6a-
tetrahydro-1H-cyclopenta[b]pyrrol-6-one skeleton). The
structure was confirmed by the X-ray analysis of the
analogue (4b) derived from the reaction of 2-butenyl(n-
propyl)amine (2b) with 1a (Figure S2 and Scheme 1).

8904 J . Org. Chem., Vol. 66, No. 26, 2001
Yoshitake et al.
Ta ble 1. P r od u ct Distr ibu tion for th e Rea ction of 1a
w ith 2a a
Sch em e 3
yield (%)
solvent
temp. (°C) time (h) 3a 4a 1z total
DMF
r.t.
r.t.
0
48
48
72
72
25 15
37 10
14 30
6
-
-
-
46
47
44
39
DMF (deairing)
DMF (deairing)
toluene (deairing)
0
8
31
a
1:1 reaction.
Sch em e 2
The structure of 1z was determined as a diepoxide of
1a on the basis of the MS data. The high-field shift of
the phenyl protons indicates the stereochemistry of the
diepoxide to be syn. The formation of 1z is suppressed
under deairing conditions (see Table 1). When a mixture
of 1a and triethylamine in toluene was stirred at room
temperature, 1z was produced. The diepoxide 1z is
considered to be derived from the [4+2]π cycloadduct of
1a and oxygen.6
Sch em e 4
The product distributions under some different condi-
tions are tabulated in Table 1. The reaction did occur
even at 0°, wherein the formation of 4a is predominant.
A dipolar aprotic solvent (DMF) was found to be a
suitable solvent for the reaction. In the case of toluene
at 0°, the formation of a small amount of the Diels-Alder
adduct was also observed. Several 2-alkenylamines were
allowed to react with 1a , but the yields were low.
Rea ction of 1a w ith 2-P r op yn yla m in es (2c-g). A
mixture of 1a and 2-propynylamine (2c) in acetonitrile
was allowed to stand at 0 °C or room temperature for 4h
under an argon gas atmosphere. The crude product was
purified by chromatography on silica gel to give 5c
(Scheme 2). Inspection of the 1H NMR and 13C NMR
spectra of 5c indicated the presence of the exocyclic vinyl
group and the three sp3 carbon atoms, except for the two
methoxy groups. The IR and visible absorption spectra
implied the presence of the phenyl-conjugated cyclopen-
tenone structure. These suggest the formation of 3-me-
thylenepyrrolidine ring.
The regiochemistry of the cyclization was established
by the single-crystal X-ray analysis, showing that the
nitrogen atom of 2c attached to the â position of the
cyclopentadienone ring (Figure S3). The Diels-Alder
reaction product was not produced, indicating that the
nitrogen lone pair is more reactive than the acetylenic π
orbitals, in accordance with the FMO consideration.
Propyl(2-propynyl)amine (2d ) reacted with 1a under
the same reaction condition to give the tetracyclic com-
pound (3d a ) (see Scheme 3).
The reactions of 2,5-bis(methoxycarbonyl)-3,4-di-
(4-methoxyphenyl)cyclopentadienone (1b) and 2,5-bis-
(methoxycarbonyl)-3,4-di(4-bromophenyl)cyclopentadi-
enone (1c) with 2d afforded the similar adducts (3d b and
3d c) (see Scheme 3).
The reactions with 1,1-Diethyl-2-propynylamine (2f)
and 1-ethynylcyclohexylamine (2g) gave the bicyclic
compound (5f,g), together with the tetracyclic compounds
(3f,g). The results are shown in Scheme 5.
As described above, the reaction with the unsubstituted
primary amine (2c) gave the bicyclic compound, whereas
the reactions with the secondary amines (2d ,g) gave the
tetracyclic compounds. The reactions with primary amines
(2f,g) branched at the R position gave mixtures of the
bicyclic and tetracyclic compounds.
In the reactions studied, a marked reactivity difference
between 2-alkenylamines and 2-alkynylamines was ob-
served. Allylamine reacted with 1a but did not produce
the bicyclic compound such as 5c obtained in the reaction
of 1a with 2c. The reaction product was a mixture of the
1,4 adduct and its 1,5 sigmatropic rearrangement prod-
uct, which readily decomposed to the starting materials.
In the formation reaction of the tetracyclic compounds
3, the substituent effect of 2-alkenyl moiety is significant.
For example, the reaction of 1a with 2-butenylpropyl-
amine (2b) gave the tetracyclic 3b (8%) and bicyclic
compounds 4b (7%) in poor yields. The difference in
reactivity between 2-alkenylamines and 2-alkynylamines
is attributable to the steric repulsion between the olefinic
protons of 2 and the residual moieties in the pericyclic
transition-state structures, besides their intrinsic reac-
tivity difference between alkene and alkyne observed in
pericyclic reactions.7
The structure was determined by comparison of the
1H NMR spectrum with that of 3e derived from the
reaction of 1a with di(2-propynyl)amine (2e), whose
structure was confirmed by the X-ray crystallography (see
Scheme 4 and Figure S4).
(6) Oxygen may be activated by light in the presence of strong
electron-donating amines. The isolation of the [4+2]π cycloadduct of
teracyclone and singlet oxygen was reported. Chan N. W. S. Chem.
Commun. 1970, 1550.
(7) Ciganek, E. Org. React. 1984, 32, 59-60 and references therein.

Cyclization of Cyclopentadienone with Alkynylamine
J . Org. Chem., Vol. 66, No. 26, 2001 8905
Sch em e 5
Rea ction Mech a n ism . The bicyclic compound (5c) is
considered to be formed from the ene reaction of the 1,4
adduct of 1a and 2c. The transition structure (TS-5c)
was successfully located by ab initio (HF) and DFT
(B3LYP) calculations at 6-31G* level without simplifica-
tion of the reaction system.8 The forming C‚‚‚C single
bond length is 2.283Å, while the two partial O‚‚‚H and
C‚‚‚H bond lengths are 1.150 and 1.487 Å, supporting
the [2π+2π+2σ] reaction in which the acetylenic and
ethylenic π bonds act as 2π and the O-H bond acts as
2σ (see Figure 2).
F igu r e 2. B3LYP/6-31G* transition structure (TS-5c) of the
intramolecular ene reaction of the 1,4 adduct of 1a and 2c.
Next, to obtain an evidence of the 1,5 sigmatropic
rearrangement of the 1,4 adduct, a model reaction was
studied using aniline. When 1a and aniline were dis-
solved in CDCl3 at room temperature, monitoring of the
ensuing reaction by analyzing the 1H NMR signals of the
OMe groups of 1a at δ 3.73, 6 at δ 3.62 and 3.82, and 7
at δ 3.38 and 3.90 revealed the initial formation of 6. As
illustrated by Figure 3, the concentration of 6 increased
rapidly until a maximum was reached (<10 min) and
then decreased gradually with increase of 7. From the
consumption of 6 and the behavior of the other composi-
tions (1a and 7, Scheme 6), it is obvious that 6 is
converted to 7, whose structure was confirmed by the
single-crystal X-ray analysis.9
In this reaction, a small amount of the 1,4 adduct (6)
was isolated from the reaction of 1a with aniline in CH3-
F igu r e 3. Time course experiment for the reaction of 1a with
aniline.
(8) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
J ohnson, B. G.; Robb, M. A.; Cheeseman, J . R.; Keith, T.; Petersson,
G. A.; Montgomery, J . A.; Raghavachari, K.; Al-Laham, M. A.;
Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.; Cioslowski, J .;
Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.; Peng, C. Y.; Ayala,
P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.; Replogle, E. S.; Gomperts,
R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.; Defrees, D. J .; Baker, J .;
Stewart, J . J . P.; Head-Gordon, M.; Gonzalez, C.; and Pople, J . A.
Gaussian 94, Revision D.4; Gaussian, Inc.: Pittsburgh, PA, 1995.
(9) Taken from: Kai, C. Master’s Thesis, Kumamoto University,
Kumamoto, J apan, 2000. The X-ray coordinates will be published
elsewhere: Yoshitake, Y.; Kai, C.; J ikyo, T.; Harano, K. Manuscript
in preparation.
CN at 0 °C. The 1,4 adduct was found to be thermally
stable. The 1,5 sigmatropic rearrangement did not occur
by only heating at 60 °C, but in the presence of aniline,
the rearrangement easily occurred. This indicates that
the base-catalyzed enolization of the carbonyl group of
the cyclopentenone moiety is required for the creation of
the 1,5 sigmatropic rearrangement reaction system (6′).
From the facts described above, the tetracyclic com-
pound is considered to be formed via the 1,5 sigmatropic

8906 J . Org. Chem., Vol. 66, No. 26, 2001
Yoshitake et al.
reactions proceed under very mild reaction conditions,10
although the dienophile moiety is not activated at all.
The DFT TS calculations (B3LYP/6-31G*) using a simpli-
fied model reaction system (GSc f TSc) suggest that
the IMDA reaction has a stepwise cycloaddition character
(see the forming C-C bond lengths in Figure 4 and the
energetics in Table 3). The UHF/AM1 or UHF/PM3 TS
calculation using the full structure also suggests the
stepwise character (Figure S5).
Sch em e 6
The IMDA reaction product (C) may transform to the
dihydro derivative (D) by the 1,5 sigmatropic rearrange-
ment of hydrogen (see Scheme 7).
The final stage of dehydrogenation mechanism is
uncertain. In the reaction of 1a with propyl(2-propynyl)-
amine (2d ) in toluene or with allyl tert-butylamine in
CHCl3, we isolated the [3,3]-sigmatropic rearrangement
product (8) of the DA adduct of 1a and the dihydropen-
tadienone (1a + 2H; Scheme 9). This seems to suggest
that 1a acts as a hydrogen acceptor. However, the
concentration change of 1a did not affect the yield of 3.
At the present time, the dehydrogenation mechanism
remains to be confirmed.
rearrangement product (B) of the 1,4 adduct (A) of 1a
and the unsaturated amines, followed by the intramo-
lecular Diels-Alder (IMDA) reaction using the styrene
moiety as diene and dehydrogenation of the IMDA adduct
(see Scheme 7).
There are two IMDA reaction pathways (I and II)
arisen from the two styrene moieties (see Scheme 8). The
AM1 or PM3 transition-state calculation rules out route
I because of the higher reaction barrier than that of route
II because of ring strain (see Table 2).
The FMO consideration for the reaction behavior of
allylic amines toward cyclopentadienones can be applied
to 2-alkyn-1-ols. Usually, 2-propyn-1-ol reacted with 1a
to give the DA adduct (9). However, in the presence of
amines, the bicyclic compound (10) was produced (Scheme
10). This may be attributed to the stabilization of the
alcoholate anion (HCtC-CH2O-) in aprotic solvents and
the acceleration of the 1,5 sigmatropic rearrangement
reaction by enolization of the cyclopentenone moiety of
the 1,4 adduct.
Styrenes are usually poor dienes in the IMDA reaction
because the initial step requires loss of aromatic reso-
nance stabilization. It is noteworthy that the IMDA
Mention should be made of a charge-transfer complex
formation. At an early stage of the reaction with primary
Sch em e 7

Cyclization of Cyclopentadienone with Alkynylamine
J . Org. Chem., Vol. 66, No. 26, 2001 8907
Sch em e 8
F igu r e 4. B3LYP/6-31G* transition structure for the model
IMDA reaction (GSc f TSc f GSc’). HF/6-31G* bond lengths
(Å) are in parenthses.
Ta ble 3. En er getics of th e Gr ou n d -sta te a n d
Tr a n sition -sta te Str u ctu r es for th e Mod el IMDA Rea ction
(GSc f TSc f GSc′)
geometry
method
Ea
∆Eb
GSc
RHF/3-21G
RHF/6-31G*
B3LYP/6-31G* -672.4115
RHF/3-21G
-664.3993
-668.1198
TSc
-664.3270
-668.0322
45.37 (GSc f TSc)
54.97 (GSc f TSc)
29.81 (GSc f TSc)
RHF/6-31G*
B3LYP/6-31G* -672.3640
B3LYP/6-31G* -672.4279 -10.29 (GSc f GSc′)
GSc’
Ta ble 2. En er getics of th e Gr ou n d -Sta te a n d
Tr a n sition -Sta te Str u ctu r es for th e IMDA Rea ction Step
in th e Rea ction of 1a w ith 2a (GS f TSa ,b f GSa ,b)
a
b
In Hartree. In kcal/mol.
a
a
charge-transfer complexation but show Diels-Alder re-
activity. It appears likely that 1,4 addition reaction
proceeds via charge-transfer complexes.
geometry
method
∆Hf
)
∆∆Hf
GS
AM1
PM3
AM
PM3
AM1
PM3
AM
PM3
AM1
PM3
-55.66
-69.84
3.03
-16.37
-10.00
-24.59
-42.30
-62.53
-72.09
-85.44
-
-
On the basis of the experimental facts, calculated TS
structures, and reaction mechanism, it is reasonable to
expect that the product in the reaction of 1a with
2-alkynylamines would depend on the stability of the 1,4
adducts of 1a and 2-alkynylamines. The addition of the
secondary amines to the 3-position of 1a produces the
overcrowded 3-(primary or secondary 2-alkynylamino)-
3,4-diphenylcyclopentenone derivatives. Therefore, for
the relief of the strain, the 1,4 adducts may isomerize to
the corresponding 1,5 sigmatropic rearrangement prod-
ucts leading to the tetracyclic compounds. In the case of
the R-branched primary amines, the steric repulsions in
the 1,4 adducts are somewhat smaller than those of the
secondary amines to give the tetracyclic compounds in
addition to the bicyclic compounds.
In conclusion, we have demonstrated that unsaturated
amines react readily with 1a to give bicyclic and/or
tetracyclic compounds in good yield. The striking differ-
ence in the reaction behavior between allylic alcohols and
allylic amines can be attributable to the character of their
HOMOs. The molecular design using multistage sequen-
tial pericyclic reaction methodology is very valuable for
construction of complexed molecules under very mild
reaction conditions. Further generalizations of these
observations and their implications for the synthesis of
TSa
TSb
GSa
GSb
58.69 (GS f TSa )
53.47 (GS f TSa )
45.66 (GS f TSb)
45.25 (GS f TSb)
13.06 (GS f GSa )
8.22 (GS f GSa )
-16.43 (GS f GSb)
-15.60 (GS f GSb)
a
In kcal/mol.
and secondary amines, perceptible transient color changes
(orange f green) were observed. The tertiary amines
such as triethylamine did not produce similar transient
color changes with 1a . These facts indicate that the
hydrogen bonding to the carbonyl functions of 1a lowers
the LUMO energy level and enhances the electron
acceptability, very favorable for charge-transfer complex-
ation. 2,5-Dimethyl, 2,5-diethyl and 2,5-diphenylcyclo-
pentadienones and phencyclone (1,3-diphenylcyclopenta-
[l]phenanthren-2-one) did not show color changes due to
(10) Campos, P. J .; Lamaza, I.; Rodriguez, M. A.; Canal, G.
Tetrahedron Lett. 1997, 38, 6741-6744. Aromatic methyleneamines
(4π) react with cyclopentadiene (2π) at 40 °C to give [4+2]π adducts.
The observed regio- and stereochemistry suggests a concerted mech-
anism for the reaction.
(11) White, D. M. J . Org. Chem. 1974, 39, 1951.

8908 J . Org. Chem., Vol. 66, No. 26, 2001
Yoshitake et al.
Ma ter ia ls. 2,5-Bis(methoxycarbonyl)-3,4-diphenylcyclopen-
tadienone11 1a was prepared according to the previously
reported method. 2,5-Bis(methoxycarbonyl)-3,4-di(4-meth-
oxyphenyl)cyclopentadienone (1b) was prepared by essentially
the same procedure as that described for 1a using CH3CN as
solvent. 2,5-Bis(methoxycarbonyl)-3,4-di(4-bromophenyl)cy-
clopentadienone (1c) was prepared using DMF as solvent.
1b: Red prisms. mp 126-127 °C (from Et2O). Yield 22%. IR
(KBr) (cm-1): 1710 (CdO). 1H NMR (300 MHz, CDCl3) δ (ppm):
3.76 (6H, s, COOCH3), 3.82 (6H, s, OMe), 6.80 (4H, d, J ) 9
Hz, Ar-H), 7.00 (4H, d, J ) 9 Hz, Ar-H). 13C NMR (125 MHz,
CDCl3) δ -(ppm): 52.0 (COOCH3), 55.2 (OMe), 113.1, 131.3
(Ar-C), 118.5, 123.1, 161.4, 162.1 (quaternary C), 163.0
(-COO), 190.9 (CdO). m/z (EI) 409 (M+ + 1). Anal. Calcd for
Sch em e 9
C
23H20O7: C, 67.64; H, 4.94. Found: C, 67.40; H, 4.78.
1c: Orange prisms. mp 234-235 °C (from acetone). Yield
40%. IR (KBr) (cm-1): 1718 (CdO). 1H NMR (300 MHz, CDCl3)
δ (ppm): 3.75 (6H, s, COOCH3), 6.91 (4H, d, J ) 9 Hz, Ar-H),
7.45 (4H, d, J ) 8 Hz, Ar-H). 13C NMR (125 MHz, CDCl3) δ
(ppm): 52.3 (COOCH3), 130.5, 131.3 (Ar-C), 119.6, 125.3,
129.3, 161.2 (quaternary C), 162.1 (-COO), 190.1 (CdO). m/z
(EI) 506 (M+). Anal. Calcd for C21H14Br2O5: C, 49.83; H, 2.79.
Found: C, 50.03; H, 2.90
Cycloa d d ition s of 1a w ith Un sa tu r a ted Am in es (Gen -
er a l P r oced u r e). A mixture of 1a (3.0 mmol) and diallylamine
(2a ) (15.0 mmol) in DMF (1 mL) was stirred at room temper-
ature. After 72 h, the reaction mixture was diluted with
benzene. The solution was 3 times washed with water. The
organic layer was separated, dried over MgSO4, and evapo-
rated to dryness. The residue was purified by column chro-
matography on silica gel with AcOEt-benzene.
Sch em e 10
With 2b-h , the following products were obtained by es-
sentially the same procedure as that described above.
P r od u cts fr om th e Rea ction of 1a w ith Dia llyla m in e
(2a). 3-Allyl-2-oxo-9c-ph en yl-2,3,4,4a,5,9c-h exah ydr o-(2aa,-
4a a ,9ca )-3-a za -p en ta len o[1,6-a b]n a p h th a len e-1,2a -d ica r -
boxylic Acid Dim eth yl Ester (3a ). Yellow prisms (37%). mp
130-131 °C (EtOH). IR (KBr)/cm-1: 1740 (enone CdO), 1706
(ester CdO). 1H NMR (500 MHz; CDCl3) δ (ppm): 2.60 (1H, t,
J ) 9 Hz, 4-Hâ), 2.94 (1H, d, J ) 18 Hz, 5-Hâ), 3.00-2.98
(2H, m, N-CH2 and 5-Ha), 3.02 (3H, s, -OMe), 3.47 (1H, dd,
J ) 9, 6 Hz, 4-Ha), 3.46-3.41 (1H, m, 4a-H), 3. 59 (1H, dd, J
) 6, 14 Hz, N-CH2), 3.89 (3H, s, -OMe), 5.09 (1H, d, J ) 10
Hz, -CHdCH2), 5.19 (1H, d, J ) 17 Hz, -CHdCH2), 5.93-
5.87 (1H, m, -CHdCH2), 7.30-7.05 (8H, m, Ar-H) and 7.70
(1H, d, J ) 8 Hz, 9-H). 13C NMR (125 MHz, CDCl3) δ (ppm):
194.8, 169.9, 168.9 (CdO), 164.5 (>C9b), 136.9 (C1), 135.5
(-CHdCH2), 117.4 (-CHdCH2), 82.8 (C2a-N), 64.7 (C9c-Ph),
53.6, 52.3, 26.3 (-CH2-), 51.7, 52.6, (-OCH3), 38.8 (C4a). m/z
(EI) 443 (M+). Anal. Calcd for C27H25NO5: C, 73.12; H, 5.68;
N, 3.16. Found: C, 73.32; H, 5.61; N, 3.33. The stereo structure
was established by the X-ray analysis.
1-Allyl-3-h yd r oxym eth yl-6-oxo-3a ,4-d ip h en yl-2,3,3a ,6-
tetr a h yd r o-(3a a ,6a a )-1H-cyclop en ta [b]p yr r ol-5,6a -d ica r -
boxylic Acid Dim eth yl Ester (4a -en d o). Yellow oil. IR
(KBr)/cm-1: 1724 (enone CdO), 1740 (ester CdO), 3496 (-OH).
1H NMR (500 MHz; CDCl3) δ (ppm): 2.49-2.52 (1H, m, 3-Hb),
3.09, 3.82 (6H, s,-OMe × 2), 2.92 (1H, dd, J ) 10, 6 Hz, 2-Hb),
3.36 (1H, d, J ) 10 Hz, 2-HR), 3.66 (1H, dd, J ) 14, 6 Hz,
N-CH2-CHd), 3.03 (1H, dd, J ) 8, 14 Hz, N-CH2-CH)),
3.85 (1H, dd, J ) 11, 4 Hz, -CH2-O), 4.14 (1H, dd, J ) 11,
4 Hz, -CH2-O), 5.14 (1H, d, J ) 10 Hz, -CHdCH2), 5.24
(1H, d, J ) 17 Hz, -CHdCH2), 5.58 (1H, dddd, J ) 17, 10, 8,
6 Hz, -CHdCH2) and 7.27-7.52 (10H, m, Ar-H). 13C NMR
(125 MHz, CDCl3) δ (ppm): 194.8 (C6), 176.3 (C4), 169.2
(C6a-COO-), 164.3 (C5-COO-), 135.2 (-CHdCH2), 117.9
(-CH)CH2), 83.8 (C6a), 70.6 (C3a-Ph), 63.0 (CH2-O), 54.0
(C2), 52.2 (N-CH2-CHd), 52.6, 52.1 (-OCH3), 45.7(C3). m/z
(EI) 461 (M+). HRMS Calcd for C27H27NO6 (M+): 461.1826.
Found: 461.1838.
various heterocyclic compounds are the object of ongoing
investigations.
Exp er im en ta l Section
Melting points were uncorrected. The IR spectra were taken
with a Hitachi 270-30 spectrophotometer. 1H NMR and 13C
NMR spectra were taken with J EOL J NM-EX 270 (270 MHz),
J NM-AL 300 (300 MHz), and J NM-A 500 (500 MHz) spec-
trometers for ca..10% solution with TMS as an internal
standard; chemical shifts are expressed as δ values, and the
coupling constants (J ) are expressed in Hz. UV spectra were
recorded on a Shimadzu UV-2500PC spectrophotometer.
5-Oxo-1,2-diph en yl-3,7-dioxa-tr icyclo[4.1.0.00,4]h eptan e-
4,6-d ica r boxylic Acid Dim eth yl Ester (1z). Colorless pow-
der. mp 94-95 °C. IR (KBr)/cm-1 : 1768 (enone CdO), 1774
(ester CdO). 1H NMR (500 MHz; CDCl3) δ (ppm): 3.65 (6H, s,
-OMe × 2), 7.50-7.27 (10H, m, Ar-H). 13C NMR (125 MHz

Cyclization of Cyclopentadienone with Alkynylamine
J . Org. Chem., Vol. 66, No. 26, 2001 8909
CDCl3): 188.1(CdO), 141.0(COO), 53.1(OMe), 61.3(C-Ph), 76.7-
(C-COOMe). m/z (EI) 380 (M+). HRMS Calcd for C21H16NO7
(M+): 380.0872. Found: 380.0896.
P r od u cts fr om th e Rea ction of 1a w ith 2-Bu ten ylp r o-
p yla m in e (2b). According to the general method, the reaction
was performed in chloroform at 0 °C to give the tetracyclic
(8%) and bicyclic compounds (7%).
1.45-1.52 (2H, m, N-CH2-CH2-CH3), 2.86-2.95 (1H, m,
N-CH2-CH2-CH3), 3.00-3.10 (1H, m, N-CH2-CH2-CH3),
3.04 (3H, s, C2a-COOCH3), 3.86 (3H, s, C1-COOCH3), 3.97
(1H, d, J ) 11 Hz, 4-H), 4.22 (1H, d, J ) 9 Hz, 4-H), 6.44 (1H,
s, 5-H), 7.01-7.28 (8H, m, Ar-H), 7.80 (1H, d, J ) 8 Hz, 9-H).
13C NMR (75 MHz, CDCl3) δ (ppm): 11.5 (N-CH2-CH2-CH3),
22.3 (N-CH2-CH2-CH3), 51.1 (COOMe × 2), 52.3 (N-CH2-
CH2-CH3), 58.6 (C4), 65.7 (C9c), 79.8 (C2a), 120.2 (C5), 127.2,
127.3, 127.4, 127.8, 128.3, 128.9, 129.0, 131.9 (Ar-H), 127.6,
128.1, 134.0, 137.2 (quaternary C), 162.9 (C1-COO), 168.9
(C2a-COO), 177.7 (C9b), 196.9 (CdO). m/z (EI) 443 (M+). Anal.
Calcd. for C27H25NO5: C, 73.12; H, 5.68; N, 3.16. Found: C,
73.18; H, 5.66; N, 3.24.
5-Meth yl-2-oxo-9c-p h en yl-3-p r op yl-2,3,4,4a ,5,9c-h exa -
h ydr o-3-aza-pen talen o[1,6-a b]n aph th alen e-1,2a-dicar box-
ylic Acid Dim eth yl Ester (3b). Yellow oil. IR (KBr)/cm-1
:
1705 (enone CdO), 1740 (ester CdO). 1H NMR (500 MHz;
CDCl3) δ (ppm): 0.89 (3H, t, J ) 7 Hz, -CH2-CH2-CH3), 1.42
(3H, d, J ) 7 Hz, 5-Me), 1.59-1.52 (2H, m, -CH2-CH2-CH3),
2.56 (1H, dd, J ) 11, 9 Hz, 4b-H), 2.41-2.36 (1H, m, N-CH2),
2.75-2.69 (1H, m, N-CH2), 3.03 (3H, s, -OCH3), 3.13-3.10
(1H, m, 5a-H), 3.41 (1H, dd, J ) 6, 11 Hz, 4a-H), 3.50-3.47
(1H, m, 4a-H), 3.92 (3H, s, -OCH3), 7.37-7.18 (8H, m, Ar-
H) and 7.76 (1H, d, J ) 7 Hz, 9-H). 13C NMR (125 MHz CDCl3)
δ (ppm): 194.2 (>CdO), 170.1 (C2a-COO), 167.9 (C9b), 164.8
(C1-COO), 83.8 (C2a), 65.0 (C9c), 51.8 (C4), 50.6 (N-CH2),
21.9 (CH2), 45.0 (C4a), 30.2 (C5),19.2 (C5-CH3), 11.6 (CH3).
m/z (EI) 459 (M+). HRMS Calcd for C28H29NO5 (M+): 459.2046.
Found: 459.2039.
In the reaction of 1a with 2d in toluene, small amounts of
the byproducts (8, 11) were isolated. The product 11 is the
aromatized compound of the Diels-Alder adduct of 1a and 2d .
4-Hyd r oxy-3-oxo-1,6,7,7a -tetr a p h en yl-3,4,7,7a -tetr a h y-
dr o-4,7-m eth an o-in den e-2,3a,5,8-tetr acar boxylic Acid Tet-
r a m eth yl Ester (8). Colorless powder. mp 256-259 °C. IR
(KBr) (cm-1): 3280 (-OH), 1742 (-COO), 1705 (CdO). 1H
NMR (500 MHz, CDCl3) δ (ppm): 3.23, 3.52, 3.61, 3.93 (12H,
s, COOCH3 × 4), 4.56 (1H, s, methine), 7.00-8.00 (20H, m,
Ar-H). 13C NMR (125 MHz, CDCl3) δ (ppm): 62.1 (>CH-),
73.1 (>C(Ph)-), 77.4 (>C(COOCH3)-), 97.2 (C-OH), 162.6,
168.7, 169.8, 172.5 (-COO), 188.1 (CdO). m/z (EI) 698 (M+).
This type of compound was also isolated in the reaction of 1a
with allyl tert-butylamine.
1-Oxo-6,7-d ip h en yl-2-p r op yl-2,3-d ih yd r o-1H-isoin d ole-
5-ca r boxylic Acid Meth yl Ester (11). Orange oil. IR (KBr)
(cm-1): 1702 (CdO), 1738 (-COO). 1H NMR (500 MHz, CDCl3)
δ (ppm): 0.92 (3H, t, J ) 7 Hz, N-CH2-CH2-CH3), 1.66 (2H,
q, J ) 7 Hz, N-CH2-CH2-CH3), 3.49-3.52 (2H, m, N-CH2-
CH2-CH3), 3.52 (3H, s, COOCH3), 4.43 (2H, s, methylene),
6.96-7.40 (10H, m, Ar-H), 7.81 (1H, s, Ar-H). 13C NMR (125
MHz, CDCl3) δ (ppm): 11.3 (N-CH2-CH2-CH3), 21.5 (N-
CH2-CH2-CH3), 44.1 (N-CH2-CH2-CH3), 48.7 (methylene),
52.1 (COOCH3), 122.2, 126.7, 126.9, 127.2, 127.9, 128.1, 128.2,
128.6, 128.7, 129.8, 130.1 (Ar-C), 127.8, 132.0, 135.2, 138.3,
140.4, 140.6, 141.3 (quaternary C), 166.8 (-COO), 168.9 (Cd
O). m/z (EI) 385 (M+). HRMS Calcd for C25H23NO3 (M+):
385.16778. Found: 385.16865.
4-Meth oxyp h en yl Der iva tive (3d b). Yellow needles. mp
150-151 °C (from EtOH). IR (KBr) (cm-1): 1712 (CdO), 1732
(-COO);1H NMR (500 MHz, CDCl3) δ (ppm): 0.86 (3H, t, J )
7 Hz, N-CH2-CH2-CH3), 1.46-1.50 (2H, m, N-CH2-CH2-
CH3), 2.89-2.95 (1H, m, N-CH2-CH2-CH3), 3.02-3.05 (1H,
m, N-CH2-CH2-CH3), 3.10 (3H, s, COOCH3), 3.68, 3.74 (6H,
s ×2, OMe ×2), 3.85 (3H, s, COOCH3), 3.95 (1H, d, J ) 11 Hz,
4-H), 4.21 (1H, d, J ) 11 Hz, 4-H), 6.37 (1H, s, 5-H), 6.56-
6.66 (6H, m, Ar-H), 7.84 (1H, d, J ) 9 Hz, 9-H). 13C NMR
(125 MHz, CDCl3) δ (ppm): 11.6 (N-CH2-CH2-CH3), 22.4 (N-
CH2-CH2 CH3), 51.2, 52.3 (COOCH3 ×2), 52.4 (N-CH2-CH2-
CH3), 55.1, 55.3 (OMe ×2), 58.6 (C4), 65.6 (C9c), 79.7 (C2a),
111.8, 113.7 (Ar-C), 120.0 (C5), 131.1 (C9), 121.4, 126.3, 129.6,
136.2, 147.8, 159.0, 162.6 (quaternary C), 163.2 (C1-COO),
169.2 (C2a-COO), 178.6 (C9b), 196.7 (CdO). m/z (EI) 503 (M+).
Anal. Calcd for C29H29NO7: C, 69.17; H, 5.80; N, 2.78. Found:
C, 69.07; H, 5.80; N, 2.82.
4-Br om op h en yl Der iva tive (3d c). Yellow needles. mp
185-187 °C (from EtOH). IR (KBr) (cm-1): 1718 (CdO), 1734
(-COO). 1H NMR (300 MHz, CDCl3) δ (ppm): 0.85 (3H, t, J )
7 Hz, N-CH2-CH2-CH3), 1.44-1.54 (2H, m, N-CH2-CH2-
CH3), 2.87-2.94 (1H, m, N-CH2-CH2-CH3), 3.00-3.09 (1H,
m, N-CH2-CH2-CH3), 3.13, 3.85 (6H, s × 2, COOCH3 × 2),
3.97 (1H, d, J ) 11 Hz, 4-H), 4.19 (1H, d, J ) 11 Hz, 4-H),
6.39 (1H, s, 5-H), 7.09-7.47 (6H, m, Ar-H), 7.71 (1H, d, J )
8 Hz, 9-H). 13C NMR (75 MHz, CDCl3) δ (ppm): 11.5 (N-CH2-
3-(1-Hyd r oxyeth yl)-6-oxo-3a ,4-d ip h en yl-1-p r op yl-2,3,-
3a ,6-tetr a h yd r o-1H-cyclop en ta [b]p yr r ole-5,6a -d ica r box-
ylic Acid Dim eth yl Ester (4b-en d o). Yellow prisms. mp
174-176 °C (EtOH). IR (KBr)/cm-1: 1702 (enone CdO), 1734
(ester CdO), 3572 (-OH). 1H NMR (500 MHz; CDCl3) δ
(ppm): 0.87 (3H, t, J ) 7 Hz, -CH2-CH2-CH3), 1.07 (3H, d,
J ) 6 Hz, -Me), 1.56-1.49 (2H, m, -CH2-CH2-CH3), 2.18
(1H, d, J ) 6 Hz, 3-H), 2.57 (1H, dd, J ) 6, 9.8 Hz, 2-H), 2.81-
2.76, 2.28 (1H, dt, J ) 13, 7 Hz, -CH2-CH2CH3), 3.47 (1H, d,
J ) 10 Hz, 2-H), 3.74, 3.04 (6H, s, -OMe × 2), 4.42 (1H, q, J
) 6 Hz, >CH-OH), 7.72-7.10 (10H, m, Ar-H). 13C NMR (125
MHz CDCl3) δ (ppm): 194.6 (>CdO), 175.7 (C4), 169.7 (C6a-
COO), 164.3 (C5-COO), 84.2 (C6a), 51.1 (N-CH2-CH2-), 48.8
(C2), 52.5, 52.1 (OCH3), 64.6 (>CHOH), 49.1 (C1). m/z (EI) 477
(M+). Anal. Calcd for C28H31NO6: C, 70.42; H, 6.54; N, 2.93.
Found: C, 70.39; H, 6.40; N, 3.05. The stereo structure was
established by the X-ray analysis.
3-(1-Hyd r oxyeth yl)-6-oxo-3a ,4-d ip h en yl-1-p r op yl-2,3,-
3a ,6-tetr a h yd r o-1H-cyclop en ta [b]p yr r ole-5,6a -d ica r box-
ylic Acid Dim eth yl Ester (4b-exo). Yellow oil. IR (KBr)/
1
cm-1: 1710 (enone CdO), 1744 (ester CdO), 3032 (-OH). H
NMR (500 MHz; CDCl3) δ (ppm): 0.92 (3H, t, J ) 7 Hz, -CH2-
CH2-CH3), 1.16 (3H, d, J ) 6 Hz, -Me), 1.54-1.49 (2H, m,
-CH2-CH2-CH3), 2.67-2.64 (1H, m, 3-H), 2.74-2.68 (1H, m,
N-CH2), 3.00-2.93 (1H, m, N-CH2), 3.16 (1H, dd, J ) 7, 10
Hz, 2-H), 3.29 (1H, dd, J ) 7, 10 Hz, 2-H), 3.02 (3H, s, -OMe),
3.75 (3H, s, -OMe), 4.36-4.33 (1H, m, >CH (OH)) and 7.60-
7.26 (10H, m, Ar-H). 13C NMR (125 MHz CDCl3) δ (ppm):
195.8 (>CdO), 176.6 (C4), 169.0 (C6a-COO), 164.4 (C5-
COO), 70.4 (C3a), 56.4 (C2), 50.6(N-CH2-CH2-), 52.4, 51.5
(OCH3), 67.3 (>CHOH), 54.5 (C1). m/z (EI) 477 (M+).
P r od u cts fr om th e Rea ction of 1a w ith 2-P r op yn yl-
a m in e (2c). 3-Meth ylen e-4-oxo-6,6a -d ip h en yl-2,3,4,6a -tet-
r a h yd r o-(3a a ,6a a )-1H -cyclop en t a [b]p yr r ole-3a ,5-d ica r -
boxylic Acid Dim eth yl Ester (5c). Yellow prisms. mp 129-
130 °C. IR (KBr) cm-1: 1618, 1738 (CdO, COO). 1H NMR (500
MHz, CDCl3) δ (ppm): 3.14 (3H, s, C3a-COOCH3), 3.78 (3H,
s, C5-COOCH3), 3.62 (1H, d, J ) 14.7 Hz, 2-H), 3.92 (1H, d,
J ) 14.7 Hz, 2-H), 5.29 (1H, s, dCH), 5.38 (1H, s, dCH), 7.11-
7.53 (10H, m, Ar-H). 13C NMR (125 MHz, CDCl3) δ (ppm):
51.9 (C5-COOCH3), 52.5 (C3a-COOCH3), 50.3 (C2), 74.2
(C6a), 112.0 (dCH2), 126.7, 127.7, 128.5, 128.6, 130.9 (Ar-C),
131.2, 134.5, 137.2 (quaternary C), 145.4 (C3), 163.8 (C5-
COO), 168.2 (C3a-COO), 172.5 (C6), 192.9 (CdO). m/z (FAB)
+
404 (M +1). Anal. Calcd. for C24H21NO5: C, 71.45; H, 5.25;
N, 3.47. Found: C, 71.63; H, 5.21; N, 3.17.
CH2-CH3), 22.2 (N-CH2-CH2-CH3), 51.4, 52.5 (COOCH3
×
R ea ct ion s of 1a ,b ,c w it h P r op yl(2-p r op yn yl)a m in e
(2d ). 2-Oxo-9c-p h en yl-3-p r op yl-2,3,4,9c-tetr a h yd r o-(2a a ,
9ca )-3-a za -p en ta len o[1,6-a b]n a p h th a len e-1,2a -d ica r box-
ylic Acid Dim eth yl Ester (3d a ). Yellow needles. mp 158-
159 °C. IR (KBr) cm-1: 1726 (CdO, COO). 1H NMR (300 MHz,
CDCl3) δ (ppm): 0.86 (3H, t, J ) 7 Hz, N-CH2-CH2-CH3),
2), 52.3 (N-CH2-CH2-CH3), 58.4 (C4), 65.0 (C9c), 79.4 (C2a),
119.5 (C5), 128.3, 130.3, 130.5, 130.6 (Ar-C), 122.3, 126.6,
127.0, 128.0, 135.6, 135.9, 147.5 (quaternary C), 162.5 (C1-
COO), 168.6 (C2a-COO), 175.6 (C9b), 195.8 (CdO). m/z (EI)
602 (M+ + 1). Anal. Calcd for C27H23Br2NO5: C, 53.93; H, 3.86;
N, 2.33. Found: C, 54.16; H, 4.14; N, 2.31.

8910 J . Org. Chem., Vol. 66, No. 26, 2001
Yoshitake et al.
P r od u cts fr om th e Rea ction of 1a w ith Di(2-p r op yn yl)-
a m in e (2e). 2-Oxo-9c-p h en yl-3-p r op -2-yn yl-2,3,4,9c-tet-
r a h yd r o-(2a a ,9ca )-3-a za -p en ta len o[1,6-a b]n a p h th a len e-
1,2a -d ica r boxylic Acid Dim eth yl Ester (3e). Yellow prisms.
mp 171-174 °C (EtOH). IR (KBr) cm-1: 1680 (enone CdO.
1H NMR (500 MHz; CDCl3) δ (ppm): 2.23 (1H, t, J ) 2.4 Hz,
-CtCH), 3.03, 3.85 (3H, s, -OMe × 2), 3.88 (1H, dd, J ) 16.5,
3.1 Hz, N-CH2), 3.96 (1H, dd, J ) 16.5, 2.4 Hz, N-CH2), 4.24
(1H, d, J ) 11.0 Hz, 4-H), 4.32 (1H, dd, J ) 11.0, 2.0 Hz, 4-H),
6.47 (1H, s, 5-H), 7.02-7.83 (9H, m, Ar-H). 13C NMR (125
MHz, CDCl3) δ (ppm): 39.9, 51.3, 52.3 (OMe × 2), 58.7 (-CH2-
CtCH), 66.2 (C9c), 71.7 (-CtCH), 78.4 (C2a), 80.3 (-CtCH),
128.4 (C4a), 120.8 (C5), 127.4, 127.5, 128.0, 129.2 and 132.1
(aromatic C), 133.8, 136.9, 145.2, 162.6 and 168.2 (-COO),
178.3 (C9b) and 196.1 (CdO). m/z (EI) 439 (M+). The structure
was confirmed by the X-ray analysis.
CDCl3) δ (ppm): 22.9, 25.0, 39.6, 40.5 (spiro carbons), 51.8
(C5-COOCH3), 52.5 (C3a-COOCH3), 74.2 (C6a), 126.9, 128.4,
128.7, 129.5, 130.9 (Aromatic C), 131.5, 132.1, 139.2 (quater-
nary C), 154.1 (C3), 164.3 (C5-COO), 168.5 (C3a-COO), 174.2
(C6), 194.1 (CdO). m/z (EI) 471 (M+). Anal. Calcd. for C29H29
-
NO5: C, 73.87; H, 6.20; N, 2.97. Found: C, 73.65; H, 6.22; N,
2.93.
P r od u ct fr om th e Rea ction of 1a w ith 2-P r op yn -1-ol
(2h ). 3-Meth ylen e-4-oxo-6,6a -d ip h en yl-2,3,4,6a -tetr a h y-
d r o-(3a a ,6a a )-cyclop en ta [b]fu r a n -3a ,5-d ica r boxylic Acid
Dim eth yl Ester (10). Colorless prisms. mp 84-85 °C. IR
(KBr) cm-1: 1606, 1742 (CdO, COO). 1H NMR (500 MHz,
CDCl3) δ (ppm): 3.11 (3H, s, C3a-COOCH3), 3.84 (3H, s, C5-
COOCH3), 4.55 (1H, d, J ) 13.4 Hz, 2-H), 4.90 (1H, d, J )
13.4 Hz, 2-H), 5.32 (1H, s, dCH), 5.44 (1H, s, dCH), 7.25-
7.43 (10H, m, Ar-H). 13C NMR (125 MHz, CDCl3) δ (ppm):
52.0 (C5-COOCH3), 52.6 (C3a-COOCH3), 60.3 (C2), 73.7 (C6a),
111.4 (dCH2), 126.7, 127.7, 128.5, 128.6, 130.9 (Aromatic C),
131.2, 134.5, 137.2 (quaternary C), 143.3 (C3), 164.0 (C5-COO),
167.5 (C3a-COO), 168.2 (C6), 192.1 (CdO). m/z (FAB) 405
(M++1). Anal. Calcd. for C24H20O6: C, 71.28; H, 4.98. Found:
C, 71.13; H, 5.05.
P r od u cts fr om th e Rea ction of 1a w ith 1,1-Dieth yl-2-
p r op yn yla m in e (2f). 2,2-Dieth yl-3-m eth ylen e-4-oxo-6,6a -
d ip h en yl-2,3,4,6a -t et r a h yd r o-(3a a ,6a a )-1H -cyclop en t a -
[b]p yr r ole-3a ,5-d ica r boxylic Acid Dim eth yl Ester (5f).
Colorless powder. mp 110 °C. IR (KBr) cm-1: 1620, 1744 (Cd
1
O, COO). H NMR (500 MHz, CDCl3) δ (ppm): 0.47 (3H, t, J
) 7.3, 7.4 Hz, C2-CH2-CH3), 1.04 (3H, t, J ) 7.3 Hz, J ) 7.3
Hz, C2-CH2-CH3), 1.46 (2H, m, C2-CH2-CH3), 1.61-1.82
(2H, m, C2-CH2-CH3), 2.27 (1H, m, NH), 3.03 (C3a-3H, s,
COOCH3), 3.81 (3H, s, C5-COOCH3), 5.08 (1H, s, dCH), 5.48
(1H, s, dCH), 7.17-7.67 (10H, m, Ar-H). 13C NMR (125 MHz,
CDCl3) δ (ppm): 8.56 (C2-CH2-CH3 × 2), 31.8 (C2-CH2-
CH3), 34.8 (C2-CH2-CH3), 51.6 (C5-COOCH3), 52.5 (C3a-
COOCH3), 127.1, 127.9, 128.3, 128.7, 129.0, 129.7, 129.9, 131.1
(Ar-C), 131.5, 132.0, 139.9 (quaternary C), 150.6 (C3), 164.5
(C5-COO), 168.7 (C3a-COO), 174.5 (C6), 194.8 (CdO). m/z (EI)
458 (M+-1). Anal. Calcd. for C28H29NO5: C, 73.18; H, 6.36; N,
3.05. Found: C, 72.52; H, 6.32; N, 2.96.
4,4-Dieth yl-2-oxo-9c-p h en yl-2,3,4,9c-tetr a h yd r o-(2a a ,-
9ca )-3-a za -p en ta len o[1,6-a b]n a p h th a len e-1,2a -d ica r box-
ylic Acid Dim eth yl Ester (3f). Yellow powder. mp 155-156
°C. IR (KBr) cm-1: 1630, 1720 (CdO, COO). 1H NMR (500
MHz, CDCl3) δ (ppm): 0.86 (3H, t, J ) 6.7, 7.3 Hz, C4-CH2-
CH3), 1.11 (3H, t, J ) 7.3 Hz, C4-CH2-CH3), 1.62-1,78 (2H,
m, C4-CH2-CH3), 1.90-2.14 (2H, m, C4-CH2-CH3), 3.24
(3H, s, C2a-COOCH3), 3.85 (3H, s, C1-COOCH3), 6.17 (1H,
s, 5-H), 7.02-7.73 (8H, m, Ar-H), 7.74 (1H, d, J ) 7.9 Hz,
9-H). 13C NMR (125 MHz, CDCl3) δ (ppm): 8.1 (C4-CH2-
CH3), 9.4 (C4-CH2-CH3), 31.2 (C4-CH2-CH3), 52.1 (C1-
COOCH3), 52.4 (C2a-COOCH3), 60.4 (C4), 66.5 (C9c), 77.6
(C2a), 122.9 (C5), 127.3, 127.4, 127.6, 127.8, 128.5, 129.0, 131.7
(Ar-C), 129.1, 130.3, 134.5, 137.3 (quaternary C), 162.7 (C1-
COO), 171.5 (C2a-COO), 181.1 (C9b), 200.1 (CdO). m/z (EI)
456 (M+ - 1). Anal. Calcd. for C28H27NO5: C, 73.51; H, 5.95;
N, 3.06. Found: C, 72.38; H, 5.93; N, 2.48.
P r od u cts fr om th e Rea ction of 1a w ith 1-Eth yn ylcy-
cloh exyla m in e (2 g). Sp ir o[cycloh exa n e-1′,4-(2-oxo-9c-
p h en yl-2,3,4,9c-tetr a h yd r o-(2a a ,9ca )-3-a za -p en ta len o[1,6-
a b]n a p h th a len e)-1,2a -d ica r boxylic Acid Dim eth yl Ester
(3 g). Yellow powder. mp 130-132 °C. IR (KBr) cm-1: 1624,
1724 (CdO, COO). 1H NMR (500 MHz, CDCl3) δ (ppm): 1.32-
2.26 (10H, m, spiro methylenes), 3.26 (3H, s, C2a-COOCH3),
3.84 (3H, s, C1-COOCH3), 6.33 (1H, s, 5-H), 7.01-7.35 (8H,
m, Ar-H), 7.74 (1H d, J ) 7.3 Hz, 9-H). 13C NMR (125 MHz,
CDCl3) δ (ppm): 22.9, 25.0, 39.6, 40.5 (spiro carbons), 52.0
(C1-COOCH3), 52.3 (C2a-COOCH3), 66.3, (C9c), 77.4 (C2a),
120.3 (C5), 127.2, 127.3, 127.4, 127.8, 128.7, 129.0, 131.8 (Ar-
C), 126.8, 129.1, 134.4, 136.9 (quaternary C), 162.6 (C1-COO),
171.5 (C2a-COO), 181.9 (C9b), 200.2 (CdO). m/z (EI) 469
(M+). HRMS Calcd. for C29H27NO5 (M+): 469.1889. Found:
469.2012.
The Diels-Alder Adduct (9) is found in the reaction mix-
ture. Yellow oil. IR (Nujol) cm-1: 1774 (CdO, COO). 1H NMR
(500 MHz, CDCl3) δ (ppm): 2.85 (1H, s, OH), 3.54 (3H, s,
C-COOCH3), 3.79 (3H, s, C-COOCH3), 4.72 (2H, d, J ) 6.1
Hz, CH2), 6.93-7.44 (10H, m, Ar-H), 7.89 (1H, s, dC-H). 13
C
NMR (125 MHz, CDCl3) δ (ppm): 52.0 (C-COOCH3), 52.5 (C-
COOCH3), 63.2 (>CH2), 77.0 (CO-C-CO), 77.3 (CO-C-CO),
129.7 (H-Cd), 126.7, 126.9, 127.2, 127.3, 128.2, 129.7, 129.9
(Aromatic C), 137.7, 138.0, 138.3, 140.6 (quaternary C), 168.3
(C-COO), 169.5 (C-COO), 192.0 (CdO). m/z (FAB) 403 (M+
- 1).
Rea ction of 1a w ith An ilin e.3 A mixture of 1a (0.5 g, 1.4
mmol) and aniline (0.3 g, 3.2 mmol) in acetonitrile (2 mL) was
stirred in an ice-water bath for 3h. After evaporation of the
solvent, the residue was chromatographed on silica gel using
benzene/AcOEt ) 20:1 to give the 1,5 sigmatropic rearrange-
ment product 7 (581 mg, 90%) and the crude 1,4 adduct 6 (72
mg, 10%).
6: Yellow powder (crude). IR (KBr) cm-1 : 3368 (>NH), 1716
1
(CdO); H NMR (CDCl3) δ (ppm): 3.62 (3H, s, C2-COOMe),
3.82 (3H, s, C5-COOMe), 7.04-7.41 (15H, m, Ar-H). 13C
NMR (CDCl3) δ (ppm): 52.5, 52.6 (COOCH3 × 2), 53.9 (dCH),
59.0 (>C(NH-Ph)C-OOCH3), 144.5(>CdC-COOCH3), 163.5-
(CdCPh), 169.6, 178.3, 195.1 (>CdO).
7: Yellow prisms. mp 175°. IR (KBr) cm-1: 3368 (>NH),
1
1774, 1732, 1712 (CdO). H NMR (CDCl3) δ (ppm): 3.38 (3H,
s, C2-COOCH3), 3.90 (3H, s, C5-COOCH3), 5.29 (1H, s,
methine), 5.40 (1H, s, NH), 6.59-7.40 (15H, m, Ar-H). 13C
NMR (CDCl3) δ (ppm): 52.0, 52.5 (COOCH3 × 2), 52.8
(>CH-), 75.0 (>C(NH-Ph)COOCH3), 142.6 (>CdC-COOCH3),
164.4 (C)C-Ph), 167.8, 170.3, 196.0 (>CdO). m/z (EI) 441
(M+). The structure was confirmed by the X-ray analysis.9
Sin gle-Cr ysta l X-r a y An a lyses of th e P r od u cts. Mo-
lecu la r Str u ctu r e of 3a . Single crystals of the compound 3a
were prepared by slow evaporation of an ethanol solution at
room temperature. The cell constants were found by a least-
squares procedure using the values of the Bragg angles of 20
reflections. Systematic absences of reflections indicate the
space group to be P21/n, a nonstandard setting of P21/c (no.
14).
All measurements were made on a Rigaku AFC-6 four-circle
autodiffractometer with a graphite monochromated Mo KR
radiation. The reflection data were collected using ω-2θ scan
technique to a maximum 2θ value of 55.0°. Of the unique
reflections measured, reflections having Io >3.00σI were used.
The structures were solved by direct method.12 The non-
Spir o[cycloh exan e-1′,4-(-3-m eth ylen e-4-oxo-6,6a-diph e-
n yl-2,3,4,6a -t et r a h yd r o-(3a a ,6a a )-1H -cyclop en t a [b]p yr -
r ole)]-3a ,5-d ica r boxylic Acid Dim eth ylester (5 g). Yellow
powder. mp 160-163 °C. IR (KBr) cm-1: 1606, 1722 (CdO,
(12) Hull, S. E.; Lessinger, I.; Germain, G.; Declercq, J .-P.; Woolfson,
M. M. MULTAN78: A System of Computer Programmes for the
Automatic Solution of Crystal Structures from X-ray Diffraction Data;
University of York: York, England, 1978. SAPI91: Hai-Fu, F. Struc-
ture Analysis Programs with Intelligent Control; Rigaku Corporation:
Tokyo, J apan, 1991.
1
COO). H NMR (500 MHz, CDCl3) δ (ppm): 0.65-2.04 (10H,
m, spiro methylenes), 2.54 (1H, s, NH), 3.08 (3H, s, C3a-
COOCH3), 3.80 (3H, s, C5-COOCH3), 5.17 (1H, s, dCH), 5.44
(1H, s, dCH), 7.17-7.65 (10H, m, Ar-H). 13C NMR (125 MHz,

Cyclization of Cyclopentadienone with Alkynylamine
J . Org. Chem., Vol. 66, No. 26, 2001 8911
hydrogen atoms were refined anisotropically and the hydrogen
atoms were refined isotropically. Some hydrogens of the
methoxycarbonyl groups were located on the calculated posi-
tions and refined. The block-diagonal least-squares refinement
was used and the unweighted (R) and weighted agreement
factors (Rw) are given.
) 8.901 (2), b ) 11.392 (3), c ) 21.125 (2) Å, â ) 94.32(1)°, V
) 2135.9(7) Å3, Z ) 4, Dc ) 1.254 gcm-3, Dm ) 1.280(aq. KI)
gcm-3, radiation Mo KR (λ ) 0.71069 Å, scan range 2θ < 55.0°,
unique data collected 4910, unique data used (I > 3.00σ(I))
3519, R ) 0.063, Rw ) 0.093.
The results are listed in Tables S9-S12.
Neutral atom scattering factors were taken from Interna-
tional Tables for X-ray Crystallography.13 All calculations were
performed on a S4-2 workstation with UNICS III Crystal
Structure Analysis Package.14
Molecu la r Str u ctu r e of 3e. Single crystals were prepared
by slow evaporation of an ethanol solution at room tempera-
ture. The crystal structure determination of 3e was performed
by essentially the same manner described in 4b. At the final
stage of the refinement, four peaks appeared in the difference
Fourier map. Those were tentatively assigned to water oxygens
with a multiplicity of 0.5 and included in the further refine-
ment. In light of the quality of R facter, the space group of
P1h(#2) was selected.
Data collection and refinement parameters for 3a . Formula
C
27H25O5N, crystal system monoclinic, space group P21/n, a )
14.022(4), b ) 13.823(7), c ) 11.754(7) Å, â ) 94.21(3)°, V )
2272(2) Å3, Z ) 4, Dc ) 1.297 gcm-3, radiation Mo KR (λ )
0.71069 Å, scan range 2θ < 55.0°, unique data collected 4359,
unique data used (I > 3.00σ(I)) 2576, R ) 0.072, Rw ) 0.096.
The atomic coordinates, distances, and angles are listed in
Table S1-S4.
Data collection and refinement parameters for 3e. Formula
C
27H22NO5‚2H2O, crystal system triclinic, space group P1(-)-
(#2), a ) 9.848(2), b ) 13.201(2), c ) 9.540(2)Å, R ) 96.94(2),
â ) 107.77(2)°, γ ) 92.66(1)°, V ) 1167.9(4) Å3, Z ) 2, Dc )
1.348 gcm-3, Dm ) 1.352(aq. KI) gcm-3, radiation Mo KR (λ )
0.71069 Å, scan range 2θ < 55.0°, unique data collected 5359,
unique data used (I > 3.00σ(I)) 3506, R ) 0.075, Rw ) 0.073.
The results are listed in Tables S13-S16.
Molecu la r Str u ctu r e of 4b. Single crystals were prepared
by slow evaporation of a methanol solution at room temper-
ature. All measurements were made on a Rigaku AFC7R four-
circle autodiffractometer with a graphite monochromated Mo
KR radiation (λ ) 0.7107 Å) and a rotating anode generator.
The crystal structure determination of 4b was performed by
essentially the same manner described in 3a . After adding the
hydrogen atoms, keeping their vibrational amplitude fixed
(B(H) ) B(C) + 1.0 Å), and refining the values with anisotropic
temperature factors for all C, N, and O atoms, the full-matrix
least-squares refinements were performed. All calculations
were performed on a Silicon Graphics IRIS Indigo workstation
with teXsan Crystal Structure Analysis Package.14b,15 The
result is summarized in Tables S5-S8.
Molecu la r Or bita l Ca lcu la tion . Semiempirical MO cal-
culations were run through the ANCHOR II interface using
MOPAC6.05 on a Fujitsu S4/2 workstation (WS) or through
the CS Chem3D Pro interface using MOPAC97 on a Macintosh
G3 personal computer. The ab initio and DFT computations3
were carried out on a Scientists' Paradise Dragon AXP5A/433
computer or a HP Exemplar Technical Server TS VS2550 KS
in the Kumamoto University Information Processing Center.
The ground states (GS) were optimized by the EF routine
implemented in the MOPAC program packages using MNDO-
PM3 (PM3) approximation.5a The transition states (TS) were
located by the transition-state location routine.
Data collection and refinement parameters for 4b. Formula
C
28H31NO6, crystal system orthorhombic, space group P212121-
(#19), a ) 14.61(1), b ) 18.83(1), c ) 9.292(8) Å, V ) 2557(3)
Å3, Z ) 4, Dc ) 1.240 gcm-3, Dm ) 1.158(aq. KI) gcm-3
,
The fully optimized geometries calculated by AM1 or PM3
method were used as starting geometries for the ab initio and
DFT calculations. Graphical analysis of the MO calculation
data was performed on a Macintosh G3 personal computer.
radiation Mo KR (λ ) 0.71069 Å, scan range 2θ < 55.0°, unique
data collected 7220, unique data used (I > 3.00σ(I)) 3070, R )
0.05, Rw ) 0.042.
Molecu la r Str u ctu r e of 5c. Single crystals were prepared
by slow evaporation of an ethanol-ethyl acetate solution at
room temperature. The crystal structure determination of 5c
was performed by essentially the same manner described in
4b. Data collection and refinement parameters for 5c. Formula
Ack n ow led gm en t. We thanks Miss S. Kanzaki,
Miss M. Yamanami, Mr. K. Yamamoto, and Mr. T.
Shiraishi for experimental assistance.
C
24H21NO5, crystal system monoclinic, space group, P21/n, a
Su p p or tin g In for m a tion Ava ila ble: X-ray crystal reports
for 3a , 4b, 5c, and 3e and MO calculation data. This material
is available free charge via the Internet at http://pubs.acs.org.
This material is contained in libraries on microfiche, im-
mediately following this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
(13) Cromer, D. T.; Waber, J . T. International Tables for X-ray
Crystallography; The Kynoch Press: Birmingham, England, 1974; Vol.
IV, Table 2.2A.
(14) (a) Sakurai, T.; Kobayashi, K. Rikagaku Kenkyusho Hokoku
1979, 55, 69. Kawano, S. Koho. Comput. Center Kyushu Univ. 1983,
16, 113. (b) J ohnson, C. K. ORTEP; Report ORNL-3794; Ork Ridge
National Laboratory: Oak Ridge, TN, 1965.
(15) Crystal Structure Analysis Package; Molecular Structure Cor-
poration: 1985 and 1992.
J O015941O