Intramolecular [4+2] cycloaddition of furfurylsubstituted homoallylamines to allylhalides, acryloyl chloride and maleic anhydride

Article abstract of DOI:10.1002/jhet.5570430611

Acylation of 4-(furyl-2)-4-R-aminobut-1-enes and 4-R-4-furfurylaminobut-1- enes with maleic anhydride, acryloyl chloride or allylhalides provided 3-aza-10-oxatricyclo[5.2.1.0^1.5]decenes. The tricycles are formed via an initial amide formation followed by a stereoselective exo-IMDAF (Intramolecular Diels-Alder of Furan). In case of competing cycloaddition (for compounds possessing two furan or two dienophilic moieties) the most substituted fivemembered cycle is preferably annulated. Refluxing of 4-R-4- furfurylaminobut-1-enes in acetic anhydride led to exo-3-aza-11-oxatricyclo[6.2. 1.0^1.6]undecenes with the pseudoequatorial substituent R-4. Treatment of 3-aza-10-oxatricyclo[5.2.1.0^1.5]decenes with PPA at 90-110 °C promoted cyclic ether opening, aromatization and intramolecular cyclization reactions sequence to give the corresponding tetracyclic compounds - tetrahydroisoindolo[2,1-a]quinolines and tetrahydroisoindolo[2,1-b][2] benzazepines in good yields. Unusual products of ipso-substitution in aromatic ring were obtained on cyclization of N-p-R-substituted 2-allyl-4-oxo-3-aza-10- oxatricyclo[5.2.1.0_1.5]dec-8-enes.

Full text of DOI:10.1002/jhet.5570430611

Nov-Dec 2006
1479
Intramolecular [4+2] Cycloaddition of Furfurylsubstituted
Homoallylamines to Allylhalides, Acryloyl chloride and Maleic anhydride
Alexey V. Varlamov, Ekaterina V. Boltukhina, Fedor I. Zubkov* and Eugenia V. Nikitina
Organic Chemistry Department of Russian Peoples’ Friendship University, 6, Miklukho-Maklayia St., Moscow
117198, Russian Federation. Fax. +7 095 9550779; e-mail: fzubkov@sci.pfu.edu.ru
Konstantin F. Turchin
Center of Drugs Chemistry ꢀ All-Russian Institute for Chemical and Pharmaceutical Research, 7, Zubovskaya
St., Moscow 119815, Russian Federation
Received December 8, 2005
Me
Me
R3
H+
R2 = Ph
R = Ar, Hetaryl
R3 = H, Alkyl, OMe
O
N
O
CHO
O
O
Me
Me
Me
N
R2
R
R3
O
H+
CH2NH2
O
N
Ac
N
R2 = Bn
O
Acylation of 4-(furyl-2)-4-R-aminobut-1-enes and 4-R-4-furfurylaminobut-1-enes with maleic
anhydride, acryloyl chloride or allylhalides provided 3-aza-10-oxatricyclo[5.2.1.01,5]decenes.
The tricycles are formed via an initial amide formation followed by a stereoselective exo-
IMDAF (Intramolecular Diels-Alder of Furan). In case of competing cycloaddition (for
compounds possessing two furan or two dienophilic moieties) the most substituted
fivemembered cycle is preferably annulated. Refluxing of 4-R-4-furfurylaminobut-1-enes in
acetic anhydride led to exo-3-aza-11-oxatricyclo[6.2.1.01,6]undecenes with the pseudoequatorial
substituent R-4. Treatment of 3-aza-10-oxatricyclo[5.2.1.01,5]decenes with PPA at 90ꢀ110 °C
promoted cyclic ether opening, aromatization and intramolecular cyclization reactions sequence
to give the corresponding tetracyclic compounds ꢀ tetrahydroisoindolo[2,1-a]quinolines and
tetrahydroisoindolo[2,1-b][2]benzazepines in good yields. Unusual products of ipso-substitution
in aromatic ring were obtained on cyclization of N-p-R-substituted 2-allyl-4-oxo-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-enes.
J. Heterocyclic Chem., 43, 1479 (2006).
Introduction.
centers. The second aim was to synthesize a series of
carboxyl non substituted isoindolo[2,1-a]quinolines 2
(-benzazepines 3) as their further functionalization could
allow us to find some perspective ways for the
construction of the patented pharmacophores analogues
[9-14].
Recently we have proposed several effective
synthetic approaches to the potential biologically active
compounds such as hydrogenated hydroxyisoquinolines
1 [1,2], isoindolo[2,1-a]quinoline- 2 [3-5] and iso-
indolo[2,1-b]benzazepinecarboxylic acids
3 [6,7]
Results and Discussion.
(Scheme 1) using furylsubstituted homoallylamines 4,
5 as starting materials. Amines 4 and 5 were obtained
from easily available imines 6 and 7 correspondingly.
The intramolecular furan Diels–Alder reaction
(IMDAF) [8] between the alkenyl fragment and the
furan core in the amines 4 or 5 was the key step of the
transformations mentioned above.
The present study had two major aims. First it was
interesting to investigate the competing intramolecular
cycloaddition processes in the case of amines 4 and 5
possessing several potential diene and/or dienophilic
We have chosen the reaction sequence shown in
Scheme 1 to solve these problems basing on the array of
butenylamines 10aꢀf, 11aꢀc, and 12aꢀc as starting
materials. It is worth noting that the homoallylamines
10a,f [2], 11aꢀc [3], and 12aꢀc [6,7] were obtained and
characterized by our group earlier, and the aryl- 10b,
hetaryl substituted amines 10cꢀe were first synthesized.
Amines 10ꢀ12 (Fig. 1) were obtained in 71ꢀ86% yield
except the pyridylsubstituted compound 10e moderate
yield of which could be explained by the low solubility of

1480
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
Scheme 1
R1
R2
R1
R2
MgBr
O
N
NH2
+
O
H
O
6
O
H
R1
N
R1
R2
HO
HO
N
ref. 1
Ac2O
R1
R2
O
N
Ac
R2
O
8
1
4
Me
R1, R2 = H, Alkyl, Cycloalkyl, Ar
Me Me
ref. 3-5
R3 = Ph
N
H
O
2
O
CO2H
O
N
R3
O
O
O
HO2C
Me
O
Me
Me
N
Me
R3
9
5
ref. 6,7
R3 = Bn
Me
N
O
MgCl
3
CO2H
THF
H2N
R3
N
H
+
R3
O
O
7
O
the intermediate imine-allylmagnesium bromide complex
both in ether and THF.
As we have shown earlier [3], cycloaddition of
maleic anhydride to 4-furyl-4-aminobutenes 5 was
preceded by the preliminary N-acylation leading to
in the analogous manner through the formation of
the intermediate N-acryloyl derivative 13a (R=H).
Since the intermediates 13 possessed two dieno-
philic fragments (allyl and N-acryloyl) in their
molecules two competing ways of the [4+2] intra-
Figure 1
R
H
H
H
H
R
N
N
N
N
O
O
R
O
O
Me
Me
10f
11a-c
10a-e
Compound 10a 10b
12a-c
10c
10d
10e 10f 11a 11b 11c 12a 12b 12c
Me OMe H Me OMe
84 76 75 86 83 83 71
R
Ph C6H4OMe-p Thienyl-2 Furyl-2 Py-3
H
Yield, % 72 78 82 78 50
the formation of the intermediate maleinamide 13b
(R=CO2H, Scheme 2). Obviously the interaction
between acrylic anhydride and amine 10f proceeded
molecular cycloaddition were theoretically possible:
A (isoindole formation) and B (formation of iso-
quinolines).

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1481
Furfurylsubstituted Homoallylamines to Allylhalides
Scheme 2
amine to a triple bond (Scheme 3) resulting in the
formation of cis-N-dimethoxycarbonylvinylsubstituted
homoallylamine 16 in a quantitative yield. Cis-orientation
of the methoxycarbonyl fragments (E) was established by
comparing with the literature data [18,19].
R
O
5
1
7
O
9
14a R=H
(40%)
N
3
2
14b R=CO2H (60%)
3'
1'
8
2'
Scheme 3
[4+2]
A
E
ꢁ
O
exo-
ꢂ
5
2
7
O
E
4
(H2C=CH-CO)2O
R
8
9
ꢂꢃ
O
4
PhMe
N
N
E
ꢀ, 5 h
O
O
1
ꢀ, 8h
3
10
2
N
10f
16 (98%)
17 (45%)
E
1
O
O
O
E=CO2Me
O
DMAD,
PhMe,
20 °C, 4h
13a, 13b
E
20 °C, PhH
O
E
O
O
H
N
B
E
O
N
O
18
10d
N
E
15
O
R
While the thermal cyclization of homoallylamine 10d
was not observed even after prolonged boiling in xylene,
the intramolecular Diels-Alder reaction of its N-vinyl-
substituted analogue 16 proceeded smoothly in boiling
toluene giving exo-4-furylsubstituted isoquinoline 17. Its
Actually the way A resulting in the formation of N-
cyclohexyl substituted exo-oxoepoxyisoindolones 14
realized that was established experimentally. Reaction
proceeded regio- and stereospecifically giving corre-
sponding exo-oxoepoxyisoindolone 14a and exo-isoindo-
lonecarboxylic acid 14b in satisfactory yields. It’s worth
noting that six-membered cycle annulation (products of
type 15 formation) is commonly preferable compared to
the five-membered cycle formation (products of type 14
formation). We explain our experimental data in terms of
higher reactivity of the electron deficient olefin fragment
(viz R-CH=CHꢀCO) in IMDAF reactions compared to
the electron rich allylic one.
The structure of compounds 14a,b was established
relying on the 1H NMR spectroscopic data (see the
Experimental section). In particular, the H atoms of the
olefin fragment ꢀꢁ2=ꢀꢁ- in these compounds gave the
signals at ꢀ 5.02ꢁ5.04 (H-1ꢂ) and 5.81 (H-2ꢂ) ppm. The
exo-configuration of the Diels-Alder adducts 14 was
confirmed by comparing the values of spin-spin coupling
constants of oxabicyclo[2.2.1]heptene moiety H-atoms
with the literature data [15-17]. Thus J7,6endo value in 14b
was close to zero which fact confirmed the exo-
orientation of CO2H-group and 5-amide substituent. In
case of exo-orientation 6-H atom would give a signal with
J6exo,7 greater than 3 Hz (usually 4.0ꢁ4.5 Hz) [15]. The
spatial structure of the adduct 14a was established in the
same manner.
1
stereochemistry was established based on the ꢁ NMR
data. Thus the exo-orientation of ꢀ5ꢁꢀ6 bond in the
oxabicyclo[2.2.1]heptene fragment was determined
similarly to the compounds 8 [2], and the pseudooequa-
torial position of the 4-furyl substituent (cis- in relation
to the oxa-bridge) was confirmed by considering
J4,5ax=11.0 and J4,5eqv=7.0 Hz values. According to these
values as well as by analogy with the 4-thienyl-
substituted tricycle 26c (as indicated below, Fig. 2) the
piperidine moiety in the molecule of 17 has the “slightly
twisted tub” conformation. Obviously the easiness of
thermal [4+2] cycloaddition in case of alkene 16 was
determined by the flattening of the amide fragment
owing to the conjugation of the unshared electron pair of
the nitrogen atom with the multiple bond, and as a
consequence the approach of the furan and allylic
substituents in the IMDAF intermediate.
It should be emphasized that the reaction of amine 10d
with double molar excess of DMAD as well as boiling of
enamine 16 with the equimolar amount of DMAD in
toluene did not lead to the formation of the prospective
pincer-addition product 18 [20-22] (Scheme 3). In each
case a mixture of DMAD addition products to both furan
rings in bisfuran 16 was isolated from a multicomponent
reaction mixture in a low combined yield along with a
small amount of isoquinoline 17. Their spatial structure
was not studied in detail.
Interaction between difuryl derivative 10d and dimethyl
acetylenedicarboxylate (DMAD) in mild reaction
conditions proceeded as Michael addition of secondary

1482
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
Scheme 4
CO2H
CO2H
O
O
O
O
O
O
[4+2]
O
O
N
N
N
O
PhH, 20 °C
20 (70%)
19
Cl
O
O
O
O
O
O
PhMe
O
10d
N
Et3N, PhMe, 25 °C
ꢀ, 2h
O
21 (93%)
1ꢃ
22 (64%)
ꢁ
ꢂ
6
5
O
3ꢃ
N
4
2ꢃ
ꢂꢃ
7
AllylBr/ K2CO3
Me2CO, 22 °C
Me2CO
O
N
2
8
O
ꢀ, 5h
1
1ꢃ
24 (33%)
23 (77%)
3ꢃ
2ꢃ
O
O
O
O
N
N
25
25*
Alkylation of amine 10d with allylbromide in the
presence of potash proceeded smoothly giving
diallylderivative 23 in good yield (Scheme 4). Heating of
furfurylamine 23 in acetone was accompanied by
considerable resinification of the reaction mixture (we
suppose it took place owing to the side intermolecular
The interaction between homoallylamine 10d and maleic
anhydride proceeded smoothly as a regio- and stereospecific
process (Scheme 4). Initially formed maleinamide 19 (was
not isolated) cyclized instantly to exo-adduct 20. The latter
was isolated as a mixture of two geometrical isomers based
on the orientation of the allyl group in relation to the 1,7-
oxabridge. The ratio of isomers was ꢀ1:6 according to the 1H
NMR spectroscopic data (Scheme 4).
1
[4+2] cycloaddition reactions). According to the H NMR
spectrum of the reaction mixture product 24 was also
formed as a mixture of geometrical isomers but only one
of them was isolated as an individual substance after the
column chromatography in 33% yield. It was not possible
to establish the orientation of allyl radical in relation to
the oxabridge. It is interesting to note that in the latter
case we observed no traces of the prospective alternative
IMDAF products such as the isomeric epoxyisoindole 25*
and isoquinoline 25 in the reaction mixture. This fact
means that when the competing intramolecular [4+2]
cycloaddition is possible the fivemembered rings 24
would preferably be formed compared to the
sixmembered ones 25 (the entropic factor). The absence
of the isomer 25* among the IMDAF products is the
example of a well known qem-dialkyl effect (angle
compression Thorpe-Ingold effect) or of the “reactive
rotamer effect” proposed by E. Jung, both phenomena
being principally the same [23-25].
Interaction between acryloyl chloride and amine 10d
in the presence of NEt3 brought to the formation of N-
acryloylamide 21 in almost a quantitative yield. The
intramolecular cyclization of diene 21 into the
epoxyisoindolone 22 began as early as at 25ꢁ30 °C that
brought to the contamination of obtained amide 21 with
1
about 7% of adduct 22 according to the H NMR data.
Heating of acryloylamide 21 in toluene led to the rapid
formation of exo-adduct 22. Exo-epoxyisoindolone 22
was isolated as a mixture of two diastereoisomers in a
ratio of ꢀ1:2 (similarly to the isomers 20).
Geometrical isomers of the isoindolones 20 and 22
were not separated. Compound 20 was isolated as
white powder almost insoluble in chloroform and
acetone. In the case of 3-aza-10-oxabicyclo[5.2.1.01,5]-
decene 22 isolated from the reaction mixture as a light-
yellow oil, separation of the geometrical isomers
appeared to be impossible owing to the equal retention
factor of these isomers.
Unsymmetrically substituted butenylamines 10aꢁd
cyclized in boiling acetic anhydride giving exo-adducts
26aꢁd in satisfactory yields (Scheme 5). The only

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1483
Furfurylsubstituted Homoallylamines to Allylhalides
Scheme 5
The X-ray analysis [26] of 3-acetyl-4-(2-thienyl)-3-aza-11-
oxatricyclo[6.2.1.01,6]undec-9-ene 26c showed that compound
ꢁ15ꢀ17NO2S crystallized in monoclinic lattice, the space group
P21/n. Oxabicyclo[2.2.1]heptene moiety of the 26c molecule
was exo-annulated at ꢁ(7)-ꢁ(8) bond with piperidine one
(Fig. 2, crystallographic numeration used). Piperidine cycle
had “twist-boat” conformation proved by the values of
torsion angles between the planes N(1)C(5)C(6)C(7),
ꢁ(5)ꢁ(6)ꢁ(7)ꢁ(8), ꢁ(6)ꢁ(7)ꢁ(8)ꢁ(9), ꢁ(7)ꢁ(8)ꢁ(9)N(1),
ꢁ(8)ꢁ(9)N(1)C(5), and ꢁ(9)N(1)C(5)ꢁ(6) equal to
32.1, ꢀ63.8, 32.7, 25.9, ꢀ62.3, and 31.8° corres-
pondingly. N(1)-Acetyl substituent in the piperidine ring
occupied the “pseudoaxial” position, and C(5)-thienyl one ꢀ
“pseudoequatorial”. H-Atom at ꢁ(7) was “pseudoaxial” oriented
in piperidine cycle (trans- according to thienyl cycle), and it was
endo-oriented in oxabicyclo[2.2.1]heptene fragment.
H
R
R
Ac2O
N
O
O
N
ꢀ, 4h
Ac
10a-e
26a-d (23-63%)
a R=Ph; b R=C6H4OMe-p; c R=Thienyl-2;
d R=Furyl-2; e R=Py-3
exception was the impossibility to produce 4-(3-pyridyl)-
substituted tricycle 26e (condensed derivative of
anabasine, R=Py-3) because of the resinification of
1
starting amine 10e in the reaction conditions. The H
NMR spectra of the obtained exo-3-aza-11-oxatricyclo-
[6.2.1.01,6]undec-9-enes 26 contained characteristic
signals of the three spin-linked bicyclic H-atoms: ꢀ-10 (d,
ꢀ 5.99ꢀ6.36 ppm), ꢀ-9 (dd, 6.26ꢀ6.42 ppm), and ꢀ-8 (dd,
4.85ꢀ4.94 ppm) with J8,9=0.9ꢀ1.8 and J9,10=5.8ꢀ6.0 Hz.
Compounds 26a,b,d were proposed to have the same
conformation of the piperidine fragment with
“pseudoequatorial” orientation of R-substituent at C-4 on
the basis of the data mentioned above above (these
products have almost identical 1H NMR data).
Noncarboxyl substituted isoindolo[2,1-a]quinolines 2
and isoindolo[2,1-b][2]benzazepines 3 were synthesized
basing on the same starting material – furylsubstituted
homoallylamines 5 (Scheme 1). Acylation of homoallyl-
amines 11aꢀc and 12aꢀc with acryloyl chloride was
carried out in boiling acetonitrile in the presence of excess
triethylamine (Scheme 6). Resulting N-phenyl(benzyl)-3-
aza-4-oxo-10-oxatricyclo [5.2.1.01,5]dec-8-enes 28aꢀf
were isolated in satisfactory to high yields. The use of
toluene as the reaction medium in case of 11c results in
lowering tricyclic product 28c yield: 48% compared to
66% in acetonitrile.
Initial acylation of furfurylamines 11, 12 with acryloyl
chloride led to the intermediate amides 27aꢀf, which
underwent further [4+2] cycloaddition to give cyclo-
adducts 28. That was confirmed using amine 11a as a
model compound. In this case two individual products
27a and 28a were isolated by column chromatography of
the reaction mixture in the ratio of 2:1 in 75% overall
yield. Their structure was confirmed based on the array of
spectroscopic data. Heating of acryloylamide 27a at 100
°C led to the tricyclic product 28a formation.
Figure 2. The X-ray crystal structures of isoquinoline 26c
But the widening of ꢀ-2 and ꢀ-4 signals (because of
the slow rotation of the acetyl fragment around the amide
bond) did not allow to determine the orientation of the C-
4 substituent using the NMR spectral data. To solve this
problem we generated a monocrystal of the tricycle 26c
and its molecular structure was unambiguously elucidated
by X-ray data (Fig. 2).
Scheme 6
H
6
O
4
O
5
O
7
N
R
O
9
[4+2]
Cl
MeCN, ꢀ, Et3N
N
O
N
R
8
R
1
2
O
exo-
Me
1'
Me
3'
2'
Me
11a-c,
12a-c
27a-f
28d 28e
28a-f (50-87%)
Compound 28a 28b
28c
Ph C6H4Me-p C6H4OMe-p Bn CH2C6H4Me-p CH2C6H4OMe-p
66 86 68 87
28f
R
Yield, % 50 64

1484
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
synthesized earlier [3] (Scheme 1). The measurements were
obtained for all the isomers 28A/28B, and the data described
below are given only for the methoxyphenyl substituted pairs of
compounds 28cA/28cB and 9A/9B (Figure 3).
1H NMR NOE values indicating the increase of Hi
intensity when Hj signal was saturated (ꢁHi{Hj}, %) are
represented in table of Figure 3 for ꢀ-2, ꢀ-5 and ꢀ-9
protons of 28cA/28cB and 9A/9B isomeric pairs in the
averaged mode: ꢁHi,Hj=[ꢁHi{Hj}+ꢁHj{Hi}]/2 (%), where Hi,
Hj: H-2, H-5, H-9; HiꢂHj.
The cycloaddition reaction proceeded stereospecifically
and only the exo-adducts 28 were formed according to the
1H NMR spectra of crude reaction mixtures. The structure
of adducts 28 was established based on ꢀ-5, ꢀ-6 and ꢀ-7
oxabicycloheptene protons J values compared to the
literature data [15,27-31] as well as by analogy with
compounds 14a, 20, 22.
Exo-3-aza-10-oxatricyclo[5.2.1.01,5]decenes 28 were isolated
as the mixtures of geometric isomers A and B (Figure 3). The
A/B isomeric ratio varied from 10/1 to 2/1 depending on the N-
substituent nature. The isomers of compounds 28aꢀe were
separated by column chromatography that allowed to thoroughly
analyse their steric structure.
Interatomic distances d (Å) between the specified
hydrogen atoms in the isomers with cis- and trans-
orientation of the 2-alkenyl fragment in relation to the
1,7-oxabridge obtained by the molecular modeling are
represented in Figure 3. The analysis of the data
summarised in the table of Figure 3 shows that ꢁꢀ -5 and
The orientation of the methallyl fragment at C-2 in the isomeric
1
pairs 28A/28B was established basing on H NMR NOE values
and by comparison of ꢀꢀ and ꢀꢁ values in these pairs. It was
interesting to compare the data received for the 28A/28B isomeric
pairs with those for the pairs of their carboxylic analogues 9
ꢀ
-2,
ꢁꢀ
values could be compared with ꢁꢀ
values only
ꢀ
-5, -9
ꢀ
-2, -9
in the case of the isomers with cis-orientation of ꢀ-2 and
ꢀ-5 protons in which molecules dꢀ-2, -5 ꢀ dꢀ-2, -9 ꢀ dꢀ
,
ꢀ
ꢀ
ꢀ
-5, -9
10
O
O
whereas in the isomers with trans-orientation of this
protons dꢀ-2, -5 and dꢀ-2, -9 appreciably exceed dꢀ
7
6
8
.
ꢀ
4
3
ꢀ
ꢀ
-5, -9
1
O
O
5
9
It is possible to note certain correlation between ꢀꢀ and
ꢀꢁ values in 28cA/28cB and 9A/9B isomeric pairs based
on their configuration established, that could be used as
the criteria for determining configuration of the analogous
compounds. Thus, the following correlations can be used
for the NMR spectra of the CDCl3 solutions: ꢀH-3' (trans) >
ꢀH-3' (cis) (ꢃꢄꢅ0.2); ꢀꢁ (cis) > ꢀꢁ (trans) (ꢃꢄꢅ2). For
H
N
N
2
H
Me
2'
3'
Me
1'
OMe
OMe
28cB cis-
28cA trans-
O
O
CO2H
CO2H
O
-9
-9
O
example, application of these correlations to the data
H
N
N
obtained for the 28aA/28aB isomeric pair in which: ꢀH-3'
H
Me
Me
(28ꢀꢁ)=2.40 and 2.54 > ꢀH-3' (28aB)=2.28 ppm; ꢀꢁ
-9
(28aB)=134.0 > ꢀꢁ-9 (28ꢀꢁ)=132.0 ppm (ꢃꢀ=2), allows to
assert that compounds 28ꢀꢁ and 28aB are the isomers
with the trans- and cis-orientation of ꢀ-2 and ꢀ-5 protons
in relation to the 1,7-oxabridge accordingly [31].
Interaction between aminobutenes 11a, 12a and
allylhalides resulted in the formation of exo-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-enes 29, 31 (Scheme 7). N-
Benzylsubstituted amine 12a easily underwent alkylation
with allylbromide at 40 °C to form the allyl derivative 30.
Cycloaddition started on boiling the reaction mixture in
acetone (established by TLC). A mixture of allyl
OMe
Interatomic dist. (calc.),
9B cis-
9A trans-
OMe
NOE, %
Isomer
9A 9B
28cA 28cB*
(trans) (cis) (trans) (cis)
d (Å)
(trans)
2.92
(cis)
2.21
2.07
2.24
ηH-2,H-5
ηH-2,H-9
<1
<1
2.5
4.5
2.5
<1
<1
2.7
3.1
3.3
2.6
2.70
ηH-5,H-9 2.2
2.21
* As the signals of 2H-3' and H-6B protons in 28cB isomer are appreciably
overlapped in CDCl3 the NOE and exact J measurements
were carried out in C6D6 solutions.
Figure 3. 1H NMR NOE values (ηHi,Hj) and interatomic distances
(d) in the isomeric pairs 28cA/28cB and 9A/9B (400 MHz, CDCl3).
Scheme 7
O
Br
N
N
Bn
N
Bn
+
K2CO3, Me2CO, 40 °C
O
H
12a (n = 1)
Me
Me
N
30 (10%)
n
29 (46%)
O
Me
O
I
Ph
11a, 12a
K2CO3, Me2CO, ꢀ
11a (n = 0)
Me
31 (48%)

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1485
Furfurylsubstituted Homoallylamines to Allylhalides
derivative 30/adduct 29 was formed in the ratio of 1/2.6
according to the C NMR data. Heating of the obtained
made their chromatographic separation impossible. In the
case of methyl substituted product 33b the isomers
formed were separated by multiple fractional crystal-
lization. It should be notified that the yield of a 33b+34b
mixture isolated after the first recrystallization was around
65 %. The low yield of products 33c+34c (30 %) was due
to the considerable resinification of the reaction mixture
in the reaction conditions.
1
mixture at 100 °C in toluene led to the formation of
30/29=1/5 mixture. N-Phenylsubstituted aminobutene 11a
underwent alkylation only after preliminary substitution of
bromine atom in allylbromide for iodine. The intermediate
allyl derivative instantly underwent [4+2] cycloaddition in
boiling acetone to form the desired tricycle 31. Obviously
it can be explained by the fact that nitrogen atom in the
intermediate N-benzyl-N-allylderivative 30 is pyramidal
(sp3), whereas in the intermediate N-phenyl-N-allyl
derivative nitrogen atom is flat (sp2) due to the conjugation
with the aromatic ring and therefore leads to the formation
of the ordered six-membered transition state that favors
[4+2] cycloaddition process.
Intramolecular cyclization of the methallyl fragment in
tricycles 28aꢀf was carried out in PPA at 90ꢀ110 °ꢀ
(Scheme 8). N-Phenylsubstituted adducts 28aꢀc and N-
benzylsubstituted adduct 28d easily underwent intramol-
ecular electrophilic substitution in this reaction conditions
to give desired isoindolo[2,1-a]quinolines 32aꢀc and
isoindolo[2,1-b][2]benzazepine 33a in good yields.
Products 32aꢀc and 33a existed as single conformers with
the pseudo-axial H-6a (11b) according to the 1H NMR data.
The NOE experiment showed that compounds 33b and
34b were the isomers according to the position of the
1
methyl group in the aromatic ring. Thus the ꢁ NMR
spectrum of 33b contained the signals analogous to those
1
in the ꢁ NMR spectrum of 34b. The greatest difference
in the chemical shifts of equal multiples was observed for
the methyl-substituted benzene ring and equal to 0.05
ppm. It gave us grounds to suggest the products 33b and
34b to be the regioisomers judging by the arrangement of
the methyl-substituted benzene ring relative to the
remaining part of the molecule. This suggestion was
confirmed by measuring the NOE values indicating the
increase of Hi intensity when Hj signal was saturated
(ꢁHi{Hj}, %). On saturation of the high field signal of the
Me-13 group at ꢀ 1.50 ppm in the case of 34b or at ꢀ 1.52
ppm in the case of 33b the intensity increase of the
3
doublet signals at ꢂ 7.25 ppm with J=8.0 Hz (ꢃ=21%) or
4
at ꢀ 7.17 ppm with J=1.5 Hz (ꢃ=23%) was observed
Scheme 8
correspondingly. Since only H-1 situated alongside one of
the Me-13 groups can show the intensity increase in the
present experiment, the data obtained have given the
evidence of the fact that the methyl substituent in the
benzene ring was attached to C-2 in case of 33b, and to C-
3 in case of 34b. The analogous process occurred in the
case of 28f, but unfortunately we did not manage to
isolate the products formed (33c, 34c) in pure form.
Me
Me
6
5
3
R
PPA,
6a
2
7
28a-c
N
90-110 °C
1
8
32a-c
O
9
10
Me
12
Me
1
11
R
10
+
3
4
9
N
5
Scheme 9
8
PPA,
33a-c
O
Me
Me
Me
28d-f
Me
Me
90-110 °C
Me
O
Me
H+
- H2O
N
R
N
N
34b,c
O
28b
O
O
Compound 32a 32b 32c 33a 33b 34b 33c 34c
Me OMe H Me Me OMe OMe
Yield, % 61 70 64 61 20 15 15
Me
Me
Me
R
H
- H+
6
N
Me Me
N
O
33b
Me
Me
In the case of N-p-methyl- and N-p-methoxy-benzyl-
substituted adducts 28e,f the cyclization brought to the
formation of the mixtures containing two products
possessing benzazepine fragment in their molecules
according to the 1H NMR data. These products had almost
identical retention factor and equal molecular mass that
Me
N
O
- H+
Me
O
34b

1486
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
Formation of the unusual regioisomer 34b (34c) could
The data obtained showed that isoindolo[2,1-b][2]-
benzazepine system underwent electrophilic substitution
at milder conditions and contained a less mobile H-11b
proton compared to 8-carboxysubstituted analogues 3 [6].
In conclusion, we have shown that, starting from 2-
furfural and 2-furfurylamine, complex ring systems:
isoindolo[2,1-a]quinolines, isoindolo[2,1-b][2]benzazep-
ines and 3-aza-11-oxatricyclo[6.2.1.01,6]undecenes, could
be obtained in a few steps. The IMDAF reaction of
furfurylsubstituted homoallylamines with allylhalides,
acryloyl chloride and maleic anhydride occurred with
high stereoselectivity when competitive ways were
possible. Exo-products were exclusively formed; the
positional relationship of the oxygen bridge and the allylic
function in the diastereoisomers formed was established.
In the process of isoindolobenzazepine synthesis the
unusual ipso-substitution was discovered.
be explained in terms of ipso-substitution in the aromatic
ring. Thus, the tertiary carbo-cation formed upon
protonation of the methallyl fragment attacked the
quaternary carbon atom attached to the aminomethene
group [32-34] and subsequent 1,2-shift resulted in the
formation of the regioisomers 33b and 34b (Scheme 9).
It is significant that we have not observed similar ipso-
substitution in the synthesis of [2]benzazepines earlier
[6,7,35,36].
Unfortunately we did not succeed in carrying out the
desired cyclization of adducts 29, 31 into tetracyclic non-
oxygenated amines similar to 2, 3 (32ꢀ34). Products
formed from 29 or 31 in acidic conditions turned out to be
very unstable.
Isoindolo[2,1-b][2]benzazepines 33 underwent regio-
selective electrophilic substitution in the benzazepine unit.
Thus, heating of 33a with chloroacetylchloride in
dichloroethane in the presence of AlCl3 brought to the
formation of the acylation product 35 (Scheme 10).
Nitration of the compound 33a with the nitration mixture
at ꢀ5ꢀ0°C proceeded with high-regioselectivity giving 3-
nitrosubstituted product 36. At room temperatures
( 25°C) the selectivity of the process failed and a mixture
of mono- and dinitrosubstituted products was formed.
The position of the substituents in the aromatic ring in
the molecules of 35, 36 was established by comparison of
their NMR data with those of 3-nitro-8-carboxyisoindolo-
[2,1-b][2]benzazepine obtained earlier [6,37].
EXPERIMENTAL
All reagents were purchased from Acros Chemical Co. All
solvents were used without further purification. Melting points
were determined using a FisherꢀJohns melting point apparatus
and are uncorrected. IR spectra were obtained in KBr pellets for
solids or in thin film for oils (Fourier-transform infrared
1
spectrometer “Infralum FT-801”). NMR spectra H (400 MHz)
and 13C (100.6 MHz) were recorded for solutions (2ꢀ5%) in
deuteriochloroform or DMSO-d6 at 30°C and traces of chloroform
(1H NMR ꢀ 7.24, 13C NMR 77.00 ppm) or DMSO-d5H (1H NMR
ꢀ 2.49, 13C NMR 39.43 ppm) were used as the internal standard.
Mass spectra were obtained by electron ionization at 70 eV on a
ꢀꢁ MS 5988 mass spectrometer or a Finnegan MAT95XL
chromatomass spectrometer. The purity of the obtained substances
and the composition of the reaction mixtures were controlled by
TLC Sorbfil UV254 plates. The separation of the final products was
carried out by column chromatography on Al2O3 (activated,
neutral, 50–200 mm) or by fractional crystallization.
Scheme 10
Me
Me
N
HNO3/ H2SO4
O2N
-5 ꢀ 0°C, 1 h
O
36 (73%)
X-Ray data of compound 26c were collected on an “Inraf-Nonius
Cad-4” 3-circle diffractometer at 293 K using graphite monochro-
mated Mo Kꢁ radiation (ꢂ=0.71073 Å, ꢃ-scanning, 2=2ꢄ=60°) [38].
The structures were solved by direct methods using the SHELXS97
[39] program and refined by least-squares method in an anisotropic
approximation using the SHELXL97 package [40]. The H-atoms
were located geometrical and refined in arid approximation.
Me Me
ClCH2COCl
33a
O
AlCl3, (CH2Cl)2
N
Cl
O
35 (70%)
Crystal data for 26c [26]: crystal dimensions: 0.47 ꢅ 0.34 ꢅ
0.22 mm, colorless prisms, ꢂ15ꢀ17NO2S, M 275.36, space group
P21/n, monoclinic, a=6.422(5), b=7.546(7), c=28.130(9) Å,
ꢁ=90.77(3)°, V=1363.1 (17) Å3, d(calcd.)=1.342 g ꢅ cmꢀ3 and Z=4,
μ=0.235 cmꢀ1, F(000)=584. Intensities of 4096 reflections with
Iꢆ0.5ꢇI (3933 are independent of symmetry) were measured.
The final R1 value are 0.0592 (wR2(F2)=0.2010) for 3933 with I
ꢆ 2ꢇI (Rint=0.0176) reflections, GOOF=1.000.
Me
Me
PhNO2
ꢁ, 40 h
N
O
37 (42%)
4-R-4-N-Furfurylamino-1-butenes (10bꢀe).
The long-term reflux of tetrahydroisoindolobenzazepine
33a in nitrobenzene lead to the oxidation of the
tetrahydrobenzazepine fragment to form dihydroiso-
indolo[2,1-b][2]benzazepine 37.
Typical Procedure.
The freshly obtained [37,41] aldimine (0.30 mol) was slowly
added drop-wise to a stirred solution of allylmagnesium bromide

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1487
Furfurylsubstituted Homoallylamines to Allylhalides
J=1.9, 0.8 Hz, H-ꢅ), 7.70 (dt, 1H, J=1.8, 7.9 Hz, H-4*), 8.50 (d,
1H, J=4.8 Hz, H-6*), 8.54 (d, 1H, J=1.8 Hz, H-2*).
Anal. Calcd. for C14H16N2O: C, 73.68; H, 7.01; N, 12.28.
Found: C, 73.65; H, 7.14; N, 12.39.
prepared from allyl bromide (39 mL, 0.45 mol) and magnesium
turnings (22.0 g, 0.90 mol) in ether (300 mL) or THF (300 mL)
for 10e at reflux. After the addition of the Schiff base, the
reaction mixture was stirred for 1 h at room temperature. The
cooled reaction mixture was poured into saturated aqueous
NH4Cl solution (300 mL) under ice cooling and extracted with
ether (3 ꢀ 100 mL). The organic layer was dried over MgSO4
and concentrated. The residue was distilled in vacuo to give
products 10bꢁe as colourless oils.
3-(1-Allylcyclohexyl)-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-en-
4-on (14a).
Acrylic anhydride 6.60 mL (57.0 mmol) was added to a
solution of 2.50 g (11.4 mmol) of allylamine 10f in o-xylene (15
mL). The mixture was refluxed for 5 h (TLC monitoring). Then
the reaction mass was poured into H2O (150 mL) and
concentrated Na2CO3 solution was added until pH 10–11. The
solution was extracted with Et2O (3 ꢀ 70 mL), combined organic
layers were dried (MgSO4) and concentrated in vacuo. The crude
product was purified by column chromatography on Al2O3 (25 ꢀ
2 cm, using hexane/ethyl acetate, 30:1 as eluent). Compound
14a: white acicular crystals; yield 1.20 g (4.40 mmol, 40%); mp
95 °ꢀ (hexaneꢁethyl acetate); Rf 0.25 (hexaneꢁethyl acetate,
1:1); ir: 1667 (Nꢁꢀ=ꢁ), and 1627 (C=ꢀ) cmꢁ1; ms: m/z M+ 273
(2), 261 (3), 232 (17), 220 (3), 204 (2), 178 (3), 161 (2), 140 (3),
121 (4), 107 (2), 91 (2), 82 (8), 81 (100), 67 (5), 55 (10), 53 (9),
41 (11); 1H nmr (CDCl3, 400 MHz) ꢀ 1.31ꢁ1.61 (m, 8H,
(ꢀꢂ2)4), 1.51 (dd, 3J=8.7, 2J=11.8 Hz, H-6endo), 2.14 (m, 1H, H-
4-N-Furfurylamino-4-(4-methoxyphenyl)butene-1 (10b).
Yield 60.1 g (78%); bp 167ꢁ169 °C/4 mmHg; ir: 3320 (NH),
1
and 1612 (C=C) cmꢁ1; H nmr (CDCl3, 400 MHz) ꢀ 1.93 (brs,
1H, NH), 2.38ꢁ2.42 (m, 2H, H-3), 3.51 (d, 1H, J=14.6 Hz,
NCH2-A), 3.62 (t, 1H, J=6.9 Hz, H-4), 3.67 (d, 1H, J=14.6 Hz,
NCH2-B), 3.80 (s, 3H, OMe), 5.05 (brdd, 1H, J=1.1, 10.2 Hz, H-
1cis), 5.09 (dd, 1H, J=1.1, 16.9 Hz, H-1trans), 5.68 (m, 1H,
J=6.6, 7.6, 10.2, 16.9 Hz, H-2), 6.08 (dd, 1H, J=3.2, 0.8 Hz, H-
ꢂꢃ), 6.29 (dd, 1H, J=3.2, 1.8 Hz, H-ꢂ), 6.90 (AAꢃ, 2H, Jꢄ8.7 Hz,
H-Ph), 7.27 (BBꢃ, 2H, Jꢄ8.7 Hz, H-Ph), 7.36 (dd, 1H, J=1.8, 0.8
Hz, H-ꢅ).
Anal. Calcd. for C16H19NO2: C, 74.70; H, 7.39; N, 5.44.
Found: C, 74.74; H, 7.42; N, 5.39.
3
2
ꢁ-cyclohexyl), 2.16 (ddd, 1H, J=3.3, 4.5, J=11.8 Hz, H-6exo),
2.35 (brd, 1H, H-ꢁ-cyclohexyl), 2.42 (dd, 1H, 3J=3.3, 8.7 Hz, H-
4-N-Furfurylamino-4-(2-thienyl)butene-1 (10c).
3
2
5endo), 2.49 (dd, 1H, J=8.1, J=13.9 Hz, H-3ꢃB), 2.54 (dd, 1H,
Yield 57.3 g (82%); bp 130ꢁ131 °C/1 mmHg; ir: 3320 (NH),
2
2
3J=7.2, J=13.9 Hz, H-3ꢃA), 3.87 (d, 1H, J=11.7 Hz, H-2B),
1
and 1630 (C=C) cmꢁ1; H nmr (CDCl3, 400 MHz) ꢀ 1.91 (brs,
2
3
3.96 (d, 1H, J=11.7 Hz, H-2A), 5.03 (d, 1H, J=4.5 Hz, H-7),
5.02ꢁ5.08 (m, 2H, H-1ꢃ), 5.81 (dddd, 1H, J=7.2, 8.1, 9.4, 17.3
1H, NH), 2.47 (brt, 2H, J=6.7 Hz, H-3), 3.60 (d, 1H, J=14.7 Hz,
NCH2-A), 3.77 (d, 1H, J=14.7 Hz, NCH2-B), 3.97 (t, 1H, J=6.7
Hz, H-4), 5.05 (m, 1H, J=9.5 Hz, H-1cis), 5.08 (m, 1H, J=17.1
Hz, H-1trans), 5.69 (m, 1H, J=6.7, 9.5, 17.1 Hz, H-2), 6.09 (dd,
1H, J=3.4, 0.9 Hz, H-ꢂꢃ), 6.27 (dd, 1H, J=3.4, 1.8 Hz, H-ꢂ),
6.90ꢁ6.95 (m, 2H, J=2.1, 3.4, 4.3 Hz, H-ꢂ and H-ꢂꢃ (thienyl)),
7.19 (dd, 1H, J=2.1, 3.4 Hz, H-ꢅ (thienyl)), 7.32 (dd, 1H, J=1.8,
0.9 Hz, H-ꢅ).
3
Hz, H-2ꢃ), 6.36 (m, 2H, H-8 and ꢂ-9).
Anal. Calcd. for C17H23NO2: ꢀ, 74.72; ꢂ, 8.42; N, 5.12.
Found: ꢀ, 74.75; ꢂ, 8.37; N, 5.14.
3-(1-Allylcyclohexyl)-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-en-
4-on-6-carboxylic acid (14b).
Amine 10f 2.10 g (9.58 mmol) was dissolved in 15 mL of
benzene. Then an equimolar amount of maleic anhydride 0.94 g
(9.58 mmol) was added in one portion to the obtained solution.
The reaction mixture was stirred for 2 d at room temperature.
Then the crystalline product was collected by filtration, washed
with benzene (2 ꢀ 10 mL), ether (2 ꢀ 10 mL) and dried at 100
°C to give desired product 14b as white powder. Yield 1.82 g
(5.75 mmol, 60%); mp 87ꢁ110 °ꢀ with decomposition; ir: 1667
(ꢀ=ꢁ), 2980 (ꢁꢂ), and 1627 (C=ꢀ) cmꢁ1; ms: m/z [Mꢁ41]+ 273
(1), 261 (3), 232 (3), 204 (3), 178 (2), 176 (2), 140 (6), 121 (7),
98 (4), 94 (3), 91 (3), 82 (6), 81 (100), 79 (7), 77 (5), 67 (5), 55
Anal. Calcd. for C13H15NOS: C, 66.95; H, 6.43; N, 6.00.
Found: C, 66.96; H, 6.46; N, 6.08.
4-N-Furfurylamino-4-(2-furyl)butene-1 (10d).
Yield 50.8 g (78%); bp 133ꢁ134 °C/3 mmHg; ir: 3325 (NH),
1
and 1641 (C=C) cmꢁ1; H nmr (CDCl3, 400 MHz) ꢀ 1.87 (brs,
1H, NH), 2.51 (brt, 2H, J=6.7 Hz, H-3), 3.60 (d, 1H, J=14.7 Hz,
NCH2-A), 3.75 (d, 1H, J=14.7 Hz, NCH2-B), 3.77 (t, 1H, J=6.7
Hz, H-4), 5.07 (m, 1H, J=1.2, 17.1 Hz, H-1trans), 5.11 (m, 1H,
J=1.2, 10.1 Hz, H-1cis), 5.70 (ddt, 1H, J=6.7, 10.1, 17.1 Hz, H-
2), 6.11 (dd, 1H, J=3.1, 0.6 Hz, H-ꢂꢃ), 6.18 (dd, 1H, J=3.4, 0.6
Hz, H-ꢂꢃ*), 6.27 (dd, 1H, J=3.4, 1.8 Hz, H-ꢂ*), 6.31 (dd, 1H,
J=3.1, 1.8 Hz, H-ꢂ), 7.32 (dd, 1H, J=1.8, 0.6 Hz, H-ꢅ*), 7.36
(dd, 1H, J=1.8, 0.6 Hz, H-ꢅ).
1
(10), 53 (12), 43 (14), 41 (13); H nmr (CDCl3, 400 MHz) ꢀ
1.30ꢁ1.85 (m, 8H, (ꢀꢂ2)4), 2.10ꢁ2.30 (m, 2ꢂ), 2.53 (d, 2H,
3
3J=7.6 Hz, H-3ꢃ), 2.83 (d, 1H, J=9.2 Hz, H-6), 2.88 (d, 1H,
2
3J=9.2 Hz, ꢂ-5), 3.92 (d, 1H, J=12.2 Hz, H-2B), 4.00 (d, 1H,
Anal. Calcd. for C13H15NO2: C, 71.88; H, 6.91; N, 6.45.
Found: C, 71.98; H, 6.90; N, 6.44.
3
2J=12.2 Hz, H-2A), 5.07 (brd, 1H, J=16.2 Hz, ꢂ-1ꢃtrans), 5.09
3
3
(brd, 1H, J=10.7 Hz, H-1ꢃcis), 5.42 (brs, 1H, J=1.5 Hz, H-7),
3
3
4-N-Furfurylamino-4-(3-pyridyl)butene-1 (10e).
5.81 (m, 1H, J=7.6, 10.7, 16.2 Hz, H-2ꢃ), 6.41 (d, 1H, J=5.8
Hz, H-9), 6.52 (dd, 1H, 3J=1.5, 5.8 Hz, H-8).
Yield 34.2 g (50%); bp 139ꢁ141 °C/2 mmHg; ir: 3300 (NH),
1
and 1647 (C=C) cmꢁ1; H nmr (CDCl3, 400 MHz) ꢀ 1.99 (brs,
Anal. Calcd. for C18H23NO4: ꢀ, 68.13; ꢂ, 7.25; N, 4.41.
Found: C, 68.30; H, 7.18; N, 4.45.
1H, NH), 2.39 (dd, 2H, J=6.8, 7.0 Hz, H-3), 3.50 (d, 1H, J=14.7
Hz, NCH2-A), 3.67 (d, 1H, J=14.7 Hz, NCH2-B), 3.70 (t, 1H,
J=6.8 Hz, H-4), 5.02 (m, 1H, J=1.3, 9.5 Hz, H-1cis), 5.09 (dd,
1H, J=1.3, 17.4 Hz, H-1trans), 5.66 (m, 1H, J=6.7, 9.5, 17.4 Hz,
H-2), 6.06 (dd, 1H, J=3.2, 0.8 Hz, H-ꢂꢃ), 7.25 (brdd, 1H, J=4.8,
7.9 Hz, H-5*), 6.27 (dd, 1H, J=3.2, 1.9 Hz, H-ꢂ), 7.33 (dd, 1H,
Dimethyl (E)-2-[(1-(2-furyl)-3-butenyl)furfurylamino]-2-butene-
dioate (16).
DMAD 1.13 mL (9.21 mmol) was added to a solution of 2.0 g
(9.21 mmol) of allylamine 10d in toluene (10 mL). The mass was

1488
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
feebly getting warm and dark. The reaction mixture was stirred
for 4 h at room temperature (TLC monitoring). Then toluene was
stripped in vacuo. Compound 16: brown oil, yield 3.25 g (9.05
mmol, 98%); Rf 0.31 (hexaneꢀethyl acetate, 3 : 1); ir: 1733
(OꢀC=O), and 1680 (C=C) cmꢀ1; ms: m/z M+ 359 (9), 318 (5),
286 (5), 238 (17), 208 (4), 179 (6), 178 (11), 146 (5), 121 (26),
121 (9), 98 (17), 96 (62), 91 (12), 81 (100), 78 (21), 77 (17), 65
1
(13), 53 (42), 41 (14), 39 (25); 20 (maj): H nmr (DMSO, 400
MHz) ꢀ 2.47 (d, 1H, 3J=9.3 Hz, H-5), 2.52ꢀ2.62 (m, 2H, 2H-3ꢂ),
2.79 (d, 1H, 3J=9.3 Hz, H-6), 3.79 (dd, 1H, 3J=6.4, 3.8 Hz, H-2),
2
2
4.29 (d, 1H, J=16.1 Hz, NCH2-B), 4.58 (d, 1H, J=16.1 Hz,
NCH2-A), 4.95 (d, 1H, J=1.7 Hz, H-7), 5.11 (dd, 1H, 3J=10.2,
2J=1.8 Hz, H-1ꢂcis), 5.18 (dd, 1H, 3J=17.2, 2J=1.8 Hz, H-
3
1
103 (17), 93 (11), 91 (15), 82 (6), 81 (100), 77 (14), 53 (15); H
nmr (CDCl3, 400 MHz) ꢀ 2.71 (m, 2H, 2H-3), 3.62 (s, 3H,
3
1ꢂtrans), 5.75 (m, 1H, J=17.2, 10.2, 7.0 Hz, H-2ꢂ), 6.31 (brdd,
2
ꢀ
2ꢁꢂ), 3.94 (s, 3H, ꢀ 2ꢁꢂ), 4.13 (d, 1H, J=16.9 Hz, NCH2-
1H, 3J=3.2, 4J=0.8 Hz, H-ꢁꢂ), 6.38 (dd, 1H, 3J=3.2, 1.8 Hz, H-ꢁ),
6.44 (dd, 1H, 3J=5.8, 1.7 Hz, H-8), 6.65 (d, 1H, 3J=5.8 Hz, H-9),
A), 4.20 (d, 1H, 2J=16.9 Hz, NCH2-B), 4.56 (t, 1H, 3J=7.5 Hz, H-
3
2
3
4
4), 4.89 (s, 1H, EꢀCH=C), 5.06 (m, 1H, J=10.3, J=1.5 Hz, H-
1cis), 5.09 (m, 1H, 3J=17.1, 2J=1.5 Hz, H-1trans), 5.71 (ddt, 1H,
3J=10.3, 17.1, 7.0 Hz, H-2), 6.03 (dd, 1H, J=3.2, J=0.8 Hz, H-
ꢁꢂ*), 6.24 (dd, 1H, 3J=3.2, 4J=1.8 Hz, H-ꢁ*), 6.31 (dt, 1H, 3J=3.2,
7.57 (dd, 1H, J=1.8, J=0.8 Hz, H-ꢃ), 12.15 (brs, 1H, CO2H);
20 (min): ꢀ 2.48 (d, 1H, 3J=9.3 Hz, H-5), 2.52ꢀ2.62 (m, 2H, 2H-
3
4
3
3
3ꢂ), 2.77 (d, 1H, J=9.3 Hz, H-6), 3.97 (dd, 1H, J=10.5, 4.5 Hz,
2
2
H-2), 4.12 (d, 1H, J=16.1 Hz, NCH2-B), 4.72 (d, 1H, J=16.1
Hz, NCH2-A), 5.01 (d, 1H, 3J=1.8 Hz, H-7), 5.02 (brd, 1H,
3J~10.0 Hz, ꢃ-1ꢂcis), 5.11 (brd, 1H, 3J~17.0 Hz, H-1ꢂtrans), 5.75
3
0.8 Hz, H-ꢁꢂ), 6.33 (dd, 1H, J=3.2, 1.8 Hz, H-ꢁ), 7.28 (dd, 1H,
3J=1.7, 4J=0.8 Hz, H-ꢃ*), 7.38 (dd, 1H, 3J=1.7, 4J=0.8 Hz, H-ꢃ).
Anal. Calcd. for C19H21NO6: ꢀ, 63.50; ꢃ, 5.84; N, 3.89.
Found: ꢀ, 63.65; ꢃ, 5.70; N, 3.80.
3
4
(m, 1H, H-2ꢂ), 6.31 (brdd, 1H, J=3.2, J=0.8 Hz, H-ꢁꢂ), 6.34
(brdd, 1H, 3J=5.7, 1.8 Hz, H-8), 6.41 (dd, 1H, 3J=3.2, 1.9 Hz, H-
ꢁ), 6.47 (dd, 1H, J=5.7 Hz, H-9), 7.59 (m, 1H, 3J=1.9, 0.8 Hz,
3
Dimethyl (E)-2-[4-(2-furyl)-11-oxa-3-azatricyclo[6.2.1.01,6]-
undec-9-en-3-yl]-2-butenedioate (17).
H-ꢃ), 12.15 (brs, 1H, CO2H).
Anal. Calcd. for C17H17NO5: ꢀ, 64.76; ꢃ, 5.39; N, 4.40.
Found: ꢀ, 64.80; ꢃ, 5.42; N, 4.37.
Procedure A. DMAD 1.1 mL (9.20 mmol) was added to a
solution of 2.0 g (9.20 mmol) allylamine 10d in toluene (10
mL). The resulting mixture was refluxed for 15 h (TLC
monitoring). After removal of toluene, the crude product was
purified by column chromatography on Al2O3 (4 ꢄ 17 cm, using
hexane/ethyl acetate, 10:1 as eluent). Yield (17) 0.6 g (2.20
mmol, 24%).
Procedure B. The solution of 2.20 g (6.13 mmol) compound
16 in toluene (15 mL) was refluxed for 8 h. After removal of
toluene, the crude product was purified by column
chromatography on Al2O3 (3 ꢄ 15 cm, eluent hexane/ethyl
acetate, 10:1). Yield (17) 0.99 g (2.75 mmol, 45%).
4-N-Furfurylamino-N-acryloyl-4-(2-furyl)butene-1 (21).
Triethylamine 4.09 mL (29.30 mmol) and acryloyl chloride
1.99 mL (24.40 mmol) were added to a solution of allylamine
10d (2.12 g, 9.76 mmol) in 20 mL of toluene. The reaction mass
was feebly getting warm and white triethylamine hydrochloride
precipitated. The mixture was stirred for 5 h at room temperature
(TLC monitoring), diluted with H2O (100 mL) and a solution of
Na2CO3 was added until ꢄꢃ 9ꢀ10. The organic products were
extracted with CHCl3 (4 ꢄ 50 mL), combined organic layers
were washed with saturated Na2CO3 solution (2 ꢄ 50 mL), dried
over MgSO4 and concentrated. The column chromatography on
Al2O3 (15 ꢄ 1.5 cm, using ethyl acetate/hexane, 1:5 as eluent)
gave compound 21 2.50 g (9.00 mmol) contaminated with about
5ꢀ7 percent of tricycle 22 (according to NMR). Mobile yellow
oil, yield 93%; Rf 0.71 (ethyl acetate–hexane, 1:1); ir: 1665
Compound 17: white needles, mp 117ꢀ118.5 °ꢀ (ethyl
acetateꢀhexane); Rf 0.24 (ethyl acetateꢀhexane, 1 : 1); ir: 1726
(Oꢀꢀ= ), and 1680 (C=ꢀ) cmꢀ1; ms: m/z M+ 359 (29), 328 (9),
300 (26), 286 (32), 282 (8), 268 (11), 178 (13), 121 (8), 103
(10), 94 (45), 91 (23), 82 (7), 81 (100), 77 (21), 65 (9), 53 (22);
1H nmr (CDCl3, 400 MHz) ꢀ 1.42ꢀ1.66 (m, 3H, H-6 and H-7),
1.86 (dt, 1H, 2J=13.6, 3J=11.0 Hz, ꢃ-5ax), 2.34 (ddd, 1H,
1
(ꢀ= , and C=ꢀ) cmꢀ1; H nmr (DMSO, 400 MHz) ꢀ 2.60 (m,
3
2
2H, J=6.7, 7.6, 8.6 Hz, H-3); 3.35 (d, 1H, J=14.7 Hz, NCH2-
2
3
3
2J=13.6, J=7.0, 3.0 Hz, H-5eqv), 3.61 (s, 3H, CO2Me), 3.71 (d,
B), 3.80 (d, 1H, J=14.7 Hz, NCH2-A), 5.12 (m, 1H, J=10.1,
2J=1.8 Hz, H-1cis), 5.20 (m, 1H, J=17.1, 2J=1.8 Hz, H-1trans),
3
1H, 2J=15.1 Hz, H-2B), 3.83 (d, 1H, 2J=15.1 Hz, H-2A), 3.96 (s,
5.48 (dd, 1H, 3J=10.3, 2J=2.0 Hz, H-1ꢂcis), 5.78 (m, 1H, 3J=10.1,
17.1, 7.6 Hz, H-2), 5.81 (dd, 1H, 3J=10.3, 16.8 Hz, H-2ꢂ), 6.14
3
3H, CO2Me), 4.57 (d, 1H, J=7.0, 11.0 Hz, H-4ax), 4.85 (s, 1H,
3
EꢀCH=CE), 4.91 (dd, 1H, J=4.4, 1.7 Hz, H-8), 6.23 (dd, 1H,
3
3
4
3
3J=3.2, J=0.8 Hz, H-ꢁꢂ), 6.32 (dd, 1H, J=3.2, 1.8 Hz, H-ꢁ),
(brd, 1H, J=3.2 Hz, H-ꢁꢂ*), 6.19 (brd, 1H, J=3.2 Hz, H-ꢁꢂ),
6.31 (dd, 1H, 3J=3.2, 4J=1.8 Hz, ꢃ-ꢁ*), 6.33 (dd, 1H, 3J=3.2, 1.8
Hz, H-ꢁ), 6.39 (dd, 1H, 3J=16.8, 2J=2.1 Hz, ꢃ-1ꢂtrans), 6.43 (dd,
3
3
6.30 (dd, 1H, J=5.8, 1.4 Hz, H-9), 6.50 (d, 1H, J=5.8 Hz, H-
10), 7.36 (dd, 1H, 3J=1.8, 4J=0.8 Hz, H-ꢃ).
3
3
4
1H, J=8.6, 6.7 Hz, H-4), 7.37 (dd, 1H, J=1.8, J=0.8 Hz, H-
ꢃ*), 7.39 (dd, 1H, 3J=1.8, 4J=0.8 Hz, H-ꢃ).
Anal. Calcd. for C19H21NO6: C, 63.50; H, 5.84; N, 3.89.
Found: ꢀ, 63.68; ꢃ, 6.03; N, 3.94.
Anal. Calcd. for C16H17NO3: ꢀ, 68.32; ꢃ, 6.04; N, 4.98.
Found: C, 68.20; H, 6.09; N, 5.02.
2-Allyl-3-(2-furylmethyl)-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]-
dec-8-ene-6-carboxylic acid (20).
3-(2-Furylmethyl)-2-allyl-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-
Amine 10d 3.0 g (13.8 mmol) was added to a solution of 1.36
g (13.8 mmol) of maleic anhydride in benzene (25 mL). The
reaction mixture was stirred at 0ꢀ5 °ꢀ for 2 h. Then the
crystalline product was collected by filtration, washed with
benzene (2 ꢄ 30 mL), ether (30 mL) and dried in air to give
desired product 20. Compound 20: 3.01 g (9.66 mmol, 70%)
white powder, mixture of isomers in the ~1:6 ratio; mp
132ꢀ133.5 °ꢀ; ir: 3360 ( ꢃ), 1708 (NꢀC=O), and 1684 (C=C)
cmꢀ1; ms: m/z M+ 315 (5), 274 (5), 234 (4), 194 (53), 176 (15),
en-4-one (22).
Triethylamine (4.1 mL, 29.30 mmol) and acryloyl chloride
(2.0 mL, 24.40 mmol) were added to a solution of allylamine
10d 2.12 g (9.76 mmol) in toluene (20 mL). The reaction mass
was feebly getting warm and white triethylamine
hydrochloride precipitates. The mixture was refluxed for 3 h
(TLC monitoring), then diluted with H2O (100 mL) and a
solution of Na2CO3 was added until ꢄꢃ 9ꢀ10. The organic

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1489
Furfurylsubstituted Homoallylamines to Allylhalides
products were extracted with CHCl3 (4 ꢀ 50 mL). The
combined organic layers were washed with saturated Na2CO3
solution (2 ꢀ 50 mL), dried over MgSO4 and concentrated. The
column chromatography on Al2O3 (22 ꢀ 2 cm, using ethyl
acetate/hexane, 1:5 as eluent) gave tricycle 22 1.75 g (6.24
mmol). Viscous pale yellow oil, yield 64%; mixture of
diastereoisomers in the ~1:2 ratio; Rf 0.32 (ethyl acetate–
hexane, 1:1); ir: 1686 ( =ꢀ and C= ) cmꢁ1; ms: m/z M+ 281
(4), 240 (8), 216 (59), 160 (18), 121 (9), 98 (17), 96 (15), 81
3-(2-Furylmethyl)-2-allyl-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-
en (24).
Procedure A. A solution of amine 10d (3.0 g, 13.80 mmol) in
15 mL of acetone was added dropwise to a stirred mixture of
K2CO3 (7.6 g, 55.20 mmol) and allylbromide (2.4 mL, 27.60
mmol) in 25 mL of acetone. After the complete amine addition
the reaction mixture was refluxed for 1 h and poured into 100
mL of water. The organic products were extracted with ether (3
ꢀ 50 mL), combined organic layers were dried over MgSO4 and
evaporated to give dark-brown residue. Its further column
chromatography on Al2O3 (4 ꢀ 5 cm, using hexane/ethyl acetate,
10:1 as eluent) gave pure 24: 1.17 g (4.60 mmol), yield 33 %.
Procedure B. A solution of diallylderivative 23 2.0 g (7.78
mmol) in 10 mL of benzene was refluxed for 30 min (TLC
monitoring). Benzene was removed under reduced pressure, the
residual brown oil was purified by column chromatography on
Al2O3 (4 ꢀ 5 cm, using hexane/ethyl acetate, 10:1 as eluent) to
give 24: 0.59 g (2.33 mmol), yield 30 %.
1
(100), 77 (9), 53 (21), 41 (14); H nmr (DMSO, 400 MHz) 22
(maj): ꢀ 1.43 (m, 1H, H-6), 1.84 (m, 1H, H-6), 2.40 (m, 1H, H-
5), 2.60 (m, 2H, 3J=3.9, 6.5, 7.6 Hz, H-3ꢂ), 3.73 (d, 1H, 3J=6.5,
2
3.9 Hz, H-2), 4.27 (d, 1H, J=15.8 Hz, NCH2-B), 4.63 (d, 1H,
2J=15.8 Hz, NCH2-ꢁ), 4.95 (dd, 1H, 3J=4.4, 1.7 Hz, H-7), 5.11
3
2
3
(m, 1H, J=10.7, J=1.6 Hz, H-1ꢂcis), 5.19 (dd, 1H, J=17.1,
2J=1.6 Hz, H-1ꢂtrans), 6.19 (brd, 1H, 3J=3.2 Hz, H-ꢃꢂ),
3
5.70ꢁ5.83 (m, 1H, ꢂ-2ꢂ), 6.33 (dd, 1H, J=3.2, 1.8 Hz, H-ꢃ),
6.39 (dd, 1H, 3J=5.9, 1.7 Hz, H-8), 6.47 (dd, 1H, J=5.9 Hz, H-
3
3
4
9), 7.58 (dd, 1H, J=1.8, J=0.8 Hz, H-ꢄ); 22 (min): 1.43 (m,
1H, H-6A), 1.84 (m, 1H, H-6B), 2.40 (m, 1H, H-5), 2.60 (m,
Compound 24: pale yellow oil; Rf 0.47 (ethyl acetate–hexane,
1:1); ir: 1640 (C= ) cmꢁ1; ms: m/z M+ 257 (5), 217 (8), 216
(63), 136 (16), 121 (4), 108 (5), 94 (7), 81 (100), 77 (6), 53 (11),
3
2H, H-3ꢂ), 4.03 (d, 1H, J=10.4, 4.4 Hz, H-2), 4.11 (d, 1H,
2J=16.2 Hz, NCH2-B), 4.75 (d, 1H, 2J=16.2 Hz, NCH2-A), 4.99
(dd, 1H, 3J=4.3, 1.7 Hz, H-7), 5.12 (m, 1H, 3J=10.1, 2J=1.8 Hz,
H-1ꢂcis), 5.20 (m, 1H, 3J=17.1, 2J=1.8 Hz, H-1ꢂtrans),
1
2
41 (6); H nmr (CDCl3, 400 MHz) ꢀ 1.28 (dd, 1H, J=11.3,
3J=7.3 Hz, H-6endo), 1.66 (ddd, 1H, 2J=11.3, 3J=4.3, 2.8 Hz, H-
6exo), 1.98 (dddd, 1H, J=2.8, 7.3, 6.7, 10.4 Hz, H-5), 2.24 (dd,
3
5.56ꢁ5.66 (m, 1H, ꢂ-2ꢂ), 6.19 (brd, 1H, J=3.2 Hz, ꢂ-ꢃꢂ), 6.33
2
3
3
3
1H, J=8.2, J=10.4 Hz, H-4B), 2.30ꢁ2.45 (m, 2H, H-3ꢂ), 2.93
(dd, 1H, J=3.2, 1.8 Hz, H-ꢃ), 6.39 (dd, 1H, J=5.9, 1.7 Hz, H-
3
2
3
3
3
4
(dd, 1H, J=5.5, 7.3 Hz, H-4ꢂ), 3.23 (dd, 1H, J=8.2, J=6.7 Hz,
H-4A), 3.68 (d, 1H, 2J=14.3 Hz, H-2B), 3.88 (d, 1H, 2J=14.3 Hz,
H-2A), 4.94 (dd, 1H, 3J=4.3, 1.5 Hz, H-7), 5.12 (m, 1H, 3J=17.0,
2J=1.5 Hz, ꢂ-1ꢂtrans), 5.14 (m, 1H, 3J=10.1, 2J=1.5 Hz, H-
8), 6.47 (dd, 1H, J=5.9 Hz, H-9), 7.62 (dd, 1H, J=1.8, J=0.8
Hz, H-ꢄ).
Anal. Calcd. for C16H17NO3: C, 68.32; H, 6.04; N, 4.98.
Found: , 68.27; ꢂ, 6.09; N, 5.00.
3
1ꢂcis), 5.93 (ddt, 1H, J=17.0, 10.1, 6.4 Hz, H-2ꢂ), 6.18 (dd, 1H,
4
3
3J=3.1, J=0.8 Hz, H-ꢃꢂ), 6.24 (dd, 1H, J=5.8, 1.5 Hz, H-8),
6.29 (dd, 1H, 3J=3.1, 1.8 Hz, H-ꢃ), 6.43 (d, 1H, 3J=5.8 Hz, H-9),
7.35 (dd, 1H, 3J=1.8, 4J=0.8 Hz, H-ꢄ).
4-N-Furfurylamino-N-allyl-4-(2-furyl)butene-1 (23).
A solution of allylbromide (4.0 mL, 46.0 mmol) in 10 mL of
acetone was added dropwise to a stirred solution of homo-
allylamine 10d (5.0 g, 23.0 mmol), 8.50 g (46.0 mmol) of dry
NaI and 9.5 g (69.0 mmol) of ꢃ2 ꢀ3 in 20 mL of acetone. The
reaction mixture was stirred for 4 h at room temperature (TLC
monitoring), taken up into H2O (100 mL) and extracted with
ether (3 ꢀ 70 mL). Combined organic layers were washed with
saturated Na2CO3 solution (2 ꢀ 50 mL), dried over MgSO4 and
evaporated in vacuo. The residue (dark-red oil) was purified by
column chromatography on Al2O3 (4 ꢀ 1.5 cm, using hexane as
eluent). Compound 23: pale yellow oil 4.55 g (17.70 mmol),
yield 77%; Rf 0.58 (ethyl acetate–hexane, 1:2); ir: 1640 (C= )
cmꢁ1; ms: m/z M+ 257 (4), 217 (10), 216 (59), 136 (18), 121
Anal. Calcd. for C16H19NO2: , 74.70; ꢂ, 7.39; N, 5.44.
Found: , 74.64; ꢂ, 7.43; N, 5.57.
3-Acetyl-3-aza-11-oxatricyclo[6.2.1.01,6]undec-9-enes (26aꢁd).
Typical Procedure.
Homoallylamine 10aꢁe (0.1 mol) was refluxed in a 20-fold
molar excess of acetic anhydride for 3ꢁ6 h (TLC control).
Excess anhydride was distilled off under reduced pressure, the
residue was diluted with water (200 mL), basified with NaHCO3
to pH 9ꢁ10, extracted with ethyl acetate (3 ꢀ 70 mL), dried over
MgSO4 and evaporated. The residue was recrystallized from
hexaneꢁethyl acetate or purified by chromatography on Al2O3
(using hexane as eluent). Tricyclic compounds 26aꢁd were
isolated as colorless crystals.
1
(4), 108 (6), 94 (5), 81 (100), 77 (5), 53 (8), 41 (6); H nmr
3
(CDCl3, 400 MHz) ꢀ 2.60 (m, 2H, J=5.0, 7.6 Hz, H-3), 2.85
2
3
2
(dd, 1H, J=14.1, J=6.9 Hz, H-3ꢂB), 3.32 (ddt, 1H, J=14.1,
3J=6.9, 1.6 Hz, H-3ꢂA), 3.35 (d, 1H, J=14.7 Hz, NCH2-A),
3.80 (d, 1H, J=14.7 Hz, NCH2-B), 3.87 (t, 1H, J=7.6 Hz, H-
2
3-Acetyl-3-aza-4-phenyl-11-oxatricyclo[6.2.1.01,6]undec-9-ene
(26a).
2
3
3
2
4), 4.96 (m, 1H, J=10.1, J=1.5 Hz, H-1ꢂcis), 5.02 (m, 1H,
2
3
2
3J=17.1, J=1.5 Hz, H-1ꢂtrans), 5.12 (m, 1H, J=10.1, J=1.8
Yield 9.14 g (34%); mp 117ꢁ118 °C; ir: 1639 (C=C, and
NꢁC=O) cmꢁ1; ms: m/z M+ 269 (16), 228 (8), 227 (26), 210 (12),
208 (15), 188 (9), 186 (8), 146 (7), 138 (33), 104 (13), 96 (46),
91 (19), 81 (100), 53 (12), 43 (21); 1H nmr (CDCl3, 400 MHz) ꢀ
1.35ꢁ1.80 and 2.20ꢁ2.40 (m, 6H, H-4, 2H-5, H-6, 2H-7), 2.04
(s, 3H, Ac), 3.35 (brd, 1H, J=14.3 Hz, H-2A), 4.87 (dd, 1H,
J=1.8, 4.3 Hz, H-8), 5.01 (brd, 1H, J=14.3 Hz, H-2B), 6.28
(brdd, 1H, J=1.8, 5.8 Hz, H-9), 6.41 (d, 1H, J=5.8 Hz, H-10),
7.15ꢁ7.35 (m, 5H, H-Ph).
3
2
Hz, H-1cis), 5.20 (m, 1H, J=17.1, J=1.8 Hz, H-1trans), 5.73
3
3
(ddt, 1H, J=10.1, 17.1, 6.9 Hz, H-2ꢂ), 5.78 (m, 1H, J=10.1,
3
17.1, 7.6, 5.0 Hz, H-2), 6.14 (brd, 1H, J=3.2 Hz, H-ꢃꢂ*), 6.19
(brd, 1H, 3J=3.2 Hz, H-ꢃꢂ), 6.31 (dd, 1H, 3J=3.2, 4J=1.8 Hz, H-
3
3
ꢃ*), 6.33 (dd, 1H, J=3.2, 1.8 Hz, H-ꢃ), 7.37 (dd, 1H, J=1.8,
4J=0.8 Hz, H-ꢄ*), 7.39 (dd, 1H, 3J=1.8, 4J=0.8 Hz, H-ꢄ).
Anal. Calcd. for C16H19NO2: , 74.70; ꢂ, 7.39; N, 5.44.
Found: C, 74.76; H, 7.42; N, 5.46.

1490
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
Anal. Calcd. for C17H19NO2: C, 75.84; H, 7.06; N, 5.20.
Found: C, 75.58; H, 7.20; N, 5.25.
chromatography of isomeric mixture (0.5 g) on Al2O3 (1.5 ꢅ 20
cm, using hexane/ethyl acetate, from 50:1 to 10:1 as eluent).
2-Methallyl-3-aza-4-oxo-3-phenyl-10-oxatricyclo[5.2.1.01,5]dec-
3-Acetyl-3-aza-4-(4-methoxyphenyl)-11-oxatricyclo[6.2.1.01,6]-
8-ene (28a).
undec-9-ene (26b).
Yield 7.03 g (50%); ratio of isomers A/B = 6/1; ir: 1640
(C=C), and 1690 (NꢀC=O) cmꢀ1; ms: m/z M+ 281 (10), 226
(42), 172 (100), 135 (11), 117 (7), 91 (6), 77 (12), 55 (22).
Anal. Calcd. for C18H19NO2: C, 76.87; H, 6.76; N, 4.98.
Found: C, 76.89; H, 6.74; N, 5.16.
Yield 18.84 g (63%); mp 100ꢀ102 °C; ir: 1640 (C=C, and
NꢀC=O) cmꢀ1; ms: m/z M+ 299 (100), 257 (20), 240 (24), 238
(27), 218 (15), 195 (8), 161 (12), 134 (18), 121 (7), 81 (23), 43
1
(7); H nmr (CDCl3, 400 MHz) ꢀ 1.35ꢀ1.95 (m, 5H, 2H-5, H-6,
2H-7), 2.31 (brs, 3H, Ac), 3.13 (brd, 1H, J=15.0 Hz, H-2A),
3.77 (s, 3H, OMe), 4.75 (m, 1H, H-4), 4.88 (m, 1H, H-8), 5.45
(brd, 1H, J=15.0 Hz, H-2B), 6.28 (m, 1H, H-9), 6.39 (m, 1H, H-
10), 6.85 (AAꢁ, 2H, H-Ph), 7.20 (BBꢁ, 2H, H-Ph).
Compound 28aA.
1
Colourless oil, Rf 0.44 (ethyl acetateꢀhexane, 1:1); H nmr
Anal. Calcd. for C18H21NO3: C, 72.24; H, 7.02; N, 4.68.
Found: C, 72.30; H, 6.80; N, 4.82.
(CDCl3, 400 MHz) ꢀ 1.60 (dd, 1H, J=8.8, 11.8 Hz, H-6endo),
1.69 (s, 3H, Me-2ꢁ), 2.20 (ddd, 1H, J=3.4, 4.6, 11.8 Hz, H-
6exo), 2.40 (dd, 1H, J=10.1, 16.1 Hz, H-3ꢁB), 2.54 (dd, 1H,
J=3.9, 16.1 Hz, H-3ꢁA), 2.66 (dd, 1H, J=3.4, 8.8 Hz, H-5), 4.64
(dd, 1H, J=3.9, 10.1 Hz, H-2), 4.81 (brs, 1H, H-1ꢁA), 4.86 (brs,
1H, H-1ꢁB), 4.99 (dd, 1H, J=1.7, 4.6 Hz, H-7), 6.33 (dd, 1H,
J=1.7, 5.9 Hz, H-8), 6.47 (d, 1H, J=5.9 Hz, H-9), 7.14 (d, 2H,
J=7.8 Hz, H-Ph), 7.32 (brt, 1H, J=7.8 Hz, H-Ph), 7.43 (t, 2H,
J=7.8 Hz, H-Ph). 13C nmr (CDCl3, 100.6 MHz) ꢀ 173.1 (s, ꢀ-4),
140.4 (s, ꢀ-2ꢁ), 137.5 (s, ꢀ-1ꢁꢁ), 136.4 (d, ꢀ-8, J=175.6 Hz),
132.0 (d, ꢀ-9, J=177.8 Hz), 128.7 (d, 2ꢀ, ꢀ-3ꢁꢁ, 5ꢁꢁ, J=162.5
Hz), 125.4 (d, ꢀ-4ꢁꢁ, J=163.5 Hz), 123.1 (d, 2ꢀ, ꢀ-2ꢁꢁ, 6ꢁꢁ,
J=161.8 Hz), 113.2 (t, ꢀ-1ꢁ, J=155.7 Hz), 91.3 (s, ꢀ-1), 78.2 (d,
C-7, J=164.8 Hz), 59.4 (d, ꢀ-2, J=145.0 Hz), 46.6 (d, ꢀ-5,
J=138.0 Hz), 37.7 (t, ꢀ-3ꢁ, J=127.0 Hz), 28.6 (t, ꢀ-6, J=138.0
Hz), 22.6 (q, ꢁꢂ-2ꢁ, J=126.3 Hz).
3-Acetyl-3-aza-4-(2-thienyl)-11-oxatricyclo[6.2.1.01,6]undec-9-
ene (26c).
Yield 7.70 g (28%); mp 108ꢀ108.5 °C; ir: 1636 (C=C, and
NꢀC=O) cmꢀ1; ms: m/z M+ 275 (30), 233 (34), 216 (22), 214
(22), 194 (16), 152 (18), 138 (22), 110 (18), 97 (17), 96 (32), 91
1
(7), 81 (100), 53 (14), 43 (30); H nmr (CDCl3, 400 MHz) ꢀ
1.35ꢀ1.65, 1.70ꢀ1.95 and 2.30ꢀ2.50 (m, 5H, 2H-5, H-6, 2H-7),
2.16 (brs, 3H, Ac), 3.37 (m, 1H, H-4), 4.73 (brd, 1H, J=15.6 Hz,
H-2A), 4.89 (dd, 1H, J=1.2, 3.7 Hz, H-8), 5.41 (brd, 1H, J=15.6
Hz, H-2B), 6.30 (brdd, 1H, J=1.2, 5.8 Hz, H-9), 6.38 (d, 1H,
J=5.8 Hz, H-10), 6.90ꢀ7.00 (m, 2H, H-ꢂ and H-ꢂꢁ), 7.18 (dd,
1H, J=1.2, 4.6 Hz, H-ꢃ).
Anal. Calcd. for C15H17NO2S: C, 65.45; H, 6.18; N, 5.09.
Found: C, 65.73; H, 6.03; N, 5.16.
Compound 28aB.
3-Acetyl-3-aza-4-(2-furyl)-11-oxatricyclo[6.2.1.01,6]undec-9-ene
(26d).
White crystals, mp 112ꢀ114 °C (ethyl acetateꢀhexane); Rf
1
0.34 (ethyl acetateꢀhexane, 1 : 1); H nmr (CDCl3, 400 MHz) ꢀ
1.61 (dd, 1H, J=8.8, 11.8 Hz, H-6endo), 1.71 (s, 3H, Me-2ꢁ),
2.27 (ddd, 1H, J=3.5, 4.5, 11.8 Hz, H-6exo), 2.28 (m, 2H, H-3ꢁ),
2.53 (dd, 1H, J=3.5, 8.8 Hz, H-5), 4.76 (dd, 1H, J=6.4, 8.2 Hz,
H-2), 4.75 (brs, 1H, H-1ꢁB), 4.80 (brs, 1H, H-1ꢁA), 5.08 (dd, 1H,
J=1.7, 4.5 Hz, H-7), 6.27 (dd, 1H, J=1.7, 5.8 Hz, H-8), 6.36 (d,
1H, J=5.8 Hz, H-9), 7.20 (t, 1H, J=7.8 Hz, H-Ph), 7.27 (d, 2H,
J=7.8 Hz, H-Ph), 7.37 (t, 2H, J=7.8 Hz, H-Ph). 13C nmr (CDCl3,
100.6 MHz) ꢀ 173.4 (s, ꢀ-4), 140.3 (s, C-2ꢁ), 136.7 (s, ꢀ-1ꢁꢁ),
135.0 (d, C-8, J=175.5 Hz), 134.0 (d, C-9, J=177.0 Hz), 128.7
(d, 2C, C-3ꢁꢁ, 5ꢁꢁ, J=162.0 Hz), 126.1 (d, C-4ꢁꢁ, J=162.7 Hz),
125.3 (d, 2C, ꢀ-2ꢁꢁ, 6ꢁꢁ, J=161.5 Hz), 113.6 (t, ꢀ-1ꢁ, J=155.8
Hz), 90.3 (s, ꢀ-1), 78.2 (d, ꢀ-7, J=165.0 Hz), 58.8 (d, ꢀ-2,
J=140.5 Hz), 47.7 (d, ꢀ-5, J=136.8 Hz), 34.8 (t, ꢀ-3ꢁ, J=130.0
Hz), 28.6 (t, ꢀ-6, J=137.8 Hz), 23.0 (q, ꢁꢂ-2ꢁ, J=126.0 Hz).
Yield 5.96 g (23%); mp 114ꢀ116 °C; ir: 1667 (C=C, and
NꢀC=O) cmꢀ1; ms: m/z M+ 259 (5), 218 (6), 179 (6), 178 (54),
138 (28), 136 (31), 96 (32), 91 (8), 81 (100), 77 (6), 53 (14), 43
1
(18); H nmr (CDCl3, 400 MHz) ꢀ 1.35ꢀ1.60, 1.70ꢀ1.95 and
2.20ꢀ2.50 (m, 5H, 2H-5, H-6, 2H-7), 2.18 (brs, 3H, Ac), 3.32
(brd, 1H, J=15.3 Hz, H-2A), 4.77 (m, 1H, H-4), 4.89 (dd, 1H,
J=1.5, 4.0 Hz, H-8), 5.14 (brd, 1H, J=15.3 Hz, H-2B), 6.28
(brdd, 1H, J=1.5, 5.8 Hz, H-9), 6.37 (d, 1H, J=5.8 Hz, H-10),
6.20 (dd, 1H, J=0.9, 3.4 Hz, H-ꢂꢁ), 6.27 (dd, 1H, J=1.8, 3.4 Hz,
H-ꢂ), 7.33 (dd, 1H, J=0.9, 1.8 Hz, H-ꢃ).
Anal. Calcd. for C15H17NO3: C, 69.49; H, 6.56; N, 5.40.
Found: C, 69.65; H, 6.56; N, 5.46.
2-Methallyl-3-aza-4-oxo-10-oxatricyclo[5.2.1.01,5]dec-8-enes
(28aꢀf). Typical Procedure.
2-Methallyl-3-aza-4-oxo-3-(4-methylphenyl)-10-oxatricyclo-
[5.2.1.01,5]dec-8-ene (28b).
Acryloyl chloride (9.0 mL, 0.11 mol) was added dropwise to a
stirred solution of corresponding amine 11aꢀc or 12aꢀc (0.05
mol) and triethylamine (20.8 mL, 0.15 mol) in acetonitrile (100
mL). After the complete addition of acryloyl chloride the
reaction mixture was refluxed for 6ꢀ8 h (TLC monitoring). The
reaction mixture was cooled, poured into water (300 mL),
basified with 25 % aqueous ammonia to pH ꢄ10ꢀ11, extracted
with chloroform (6ꢅ80 mL), dried (MgSO4) and concentrated in
vacuo. Resulting residue was purified by column
chromatography on Al2O3 (3.5 ꢅ 30 cm, using hexane/ethyl
acetate, 10:1 as eluent) to give a mixture of isomers. Final
separation of the isomers 28aA and 28aB, 28bA and 28bB,
28cA and 28cB, 28dA was carried out by column
Yield 9.44 g (64%); ratio of isomers A/B = 2.7/1; ir: 1640
(C=C), and 1685 (NꢀC=O) cmꢀ1; ms: m/z M+ 295 (34), 240
(38), 186 (100), 118 (6), 91 (16), 77 (4), 65 (8), 55 (22), 39 (7).
Anal. Calcd. for C19H21NO2: C, 77.29; H, 7.12; N, 4.75.
Found: C, 77.17; H, 7.15; N, 4.66.
Compound 28bA.
White crystals, mp 106.5ꢀ108.5 °C (ethyl acetateꢀhexane); Rf
1
0.20 (ethyl acetateꢀhexane, 1:1); H nmr (CDCl3, 400 MHz) ꢀ
1.64 (dd, 1H, J=8.9, 11.8 Hz, H-6endo), 1.73 (s, 3H, Me-2ꢁ),
2.26 (ddd, 1H, J=3.3, 4.5, 11.8 Hz, H-6exo), 2.35 (s, 3H, Me-

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1491
Furfurylsubstituted Homoallylamines to Allylhalides
4ꢀꢀ), 2.42 (dd, 1H, J=10.3, 16.0 Hz, H-3ꢀB), 2.58 (dd, 1H, J=3.8,
16.0 Hz, H-3ꢀA), 2.57 (dd, 1H, J=3.3, 8.9 Hz, H-5), 4.62 (dd,
1H, J=3.8, 10.3 Hz, H-2), 4.84 (brs, 1H, H-1ꢀA), 4.90 (m, 1H,
H-1ꢀB), 5.05 (dd, 1H, J=1.7, 4.5 Hz, H-7), 6.38 (dd, 1H, J=1.7,
5.9 Hz, H-8), 6.52 (d, 1H, J=5.9 Hz, H-9), 7.18 (BBꢀ, 2H, Jꢁ8.2
Hz, H-Ph), 7.33 (AAꢀ, 2H, Jꢁ8.2 Hz, H-Ph).
4.73 (dd, 1ꢄ, J7,8=1.7, J7,6exo=4.5 Hz, ꢄ-7), 4.94 (brs, 1ꢄ, ꢄ-1ꢀ),
4.95 (brs, 1ꢄ, ꢄ-1ꢀ), 5.82 (dd, 1ꢄ, J8,9=5.8, J7,8=1.7 Hz, ꢄ-8),
6.05 (d, 1ꢄ, J=5.8 Hz, ꢄ-9), 6.89 (BBꢀ, 2ꢄ, H-3ꢀꢀ and H-5ꢀꢀ),
3
7.39 (AAꢀ, 2ꢄ, ꢄ-2ꢀꢀ and H-6ꢀꢀ); 13C nmr (ꢀDCl3, 100.6 MHz) ꢀ
173.7 (s, ꢀ-4), 157.9 (s, ꢀ-4ꢀꢀ), 140.3 (s, ꢀ-2ꢀ), 135.0 (d, ꢀ-8,
J=175.0 Hz), 134.0 (d, ꢀ-9, J=176.5 Hz), 129.4 (s, ꢀ-1ꢀꢀ), 127.1
(d, 2ꢀ, ꢀ-2ꢀꢀ and 6ꢀꢀ, J=160.3 Hz), 114.1 (d, 2ꢀ, ꢀ-3ꢀꢀ and 5ꢀꢀ,
J=160.0 Hz), 113.6 (t, ꢀ-1ꢀ, J=155.8 Hz), 90.5 (s, ꢀ-1), 78.3 (d,
ꢀ-7, J=164.5 Hz), 59.2 (d, ꢀ-2, J=140.0 Hz), 55.2 (q, ꢁꢂꢃ-4ꢀꢀ,
J=144.2 Hz), 47.6 (d, ꢀ-5, J=137.0 Hz), 35.0 (t, ꢀ-3ꢀ, J=128.5
Hz), 28.5 (t, ꢀ-6, J=137.5 Hz), 23.0 (q, ꢂꢃ-2ꢀ, J=126.3 Hz).
Compound 28bB.
White crystals, mp 96ꢂ97.5 °C (ethyl acetateꢂhexane); Rf
1
0.14 (ethyl acetateꢂhexane, 1:1); H nmr (CDCl3, 400 MHz) ꢀ
1.65 (dd, 1H, J=8.8, 11.8 Hz, H-6endo), 1.74 (s, 3H, Me-2ꢀ),
2.30 (ddd, 1H, J=3.5, 4.5, 11.8 Hz, H-6exo), 2.35 (s, 3H, Me-
4ꢀꢀ), 2.30 (d, 2H, J=7.4 Hz, H-3ꢀ), 2.68 (dd, 1H, J=3.5, 8.8 Hz,
H-5), 4.75 (t, 1H, J=7.4 Hz, H-2), 4.77 (dd, 1H, J=0.8, 1.4 Hz,
H-1ꢀB), 4.83 (t, 1H, J=0.8 Hz, H-1ꢀA), 5.12 (dd, 1H, J=1.7, 4.5
Hz, H-7), 6.30 (dd, 1H, J=1.7, 5.8 Hz, H-8), 6.39 (d, 1H, J=5.8
Hz, H-9), 7.15ꢂ7.22 (AAꢀBBꢀ, 4H, H-Ph).
2-Methallyl-3-aza-4-oxo-3-benzyl-10-oxatricyclo[5.2.1.01,5]dec-
8-ene (28d).
Colourless oil, yield 12.68 g (86%); ratio of isomers A/B =
10/1; ir: 1640 (C=C), and 1685 (NꢂC=O) cmꢂ1; Rf 0.17 (ethyl
acetateꢂhexane, 1:5); ms: m/z M+ 295 (9), 240 (53), 186 (100),
160 (4), 134 (2), 106 (8), 91 (84), 65 (8), 55 (24), 27 (4); 1H nmr
(CDCl3, 400 MHz, isomer A) ꢀ 1.60 (dd, 1H, J=8.8, 11.6 Hz, H-
6endo), 1.70 (s, 3H, Me-2ꢀ), 2.24 (ddd, 1H, J=2.9, 4.5, 11.6 Hz,
H-6exo), 2.37 (dd, 1H, J=8.1, 15.3 Hz, H-3ꢀB), 2.51 (dd, 1H,
J=5.7, 15.3 Hz, H-3ꢀA), 2.56 (dd, 1H, J=2.9, 8.8 Hz, H-5), 3.89
(dd, 1H, J=5.7, 8.1 Hz, H-2), 4.05 (d, 1H, J=15.3 Hz, NCH2-B),
4.82 (brs, 1H, H-1ꢀA), 4.90 (brs, 1H, H-1ꢀB), 5.03 (dd, 1H,
J=1.6, 4.5 Hz, H-7), 5.10 (d, 1H, J=15.3 Hz, NCH2-A), 6.33
(dd, 1H, J=1.6, 5.9 Hz, H-8), 6.43 (d, 1H, J=5.9 Hz, H-9),
7.19ꢂ7.33 (m, 5H, H-Ph). Anal. Calcd. for C19H21NO2: C, 77.29;
H, 7.12; N, 4.75. Found: C, 77.41; H, 7.18; N, 4.76.
2-Methallyl-3-aza-4-oxo-3-(4-methoxyphenyl)-10-oxatricyclo-
[5.2.1.01,5]dec-8-ene (28c).
Yield 10.26 g (66%); ratio of isomers A/B = 2/1; ir: 1640
(C=C), and 1685 (NꢂC=O) cmꢂ1; ms: m/z M+ 311 (48), 256
(28), 202 (100), 186 (9), 117 (8), 77 (10), 65 (4), 55 (29), 39 (7).
Anal. Calcd. for C19H21NO3: C, 73.31; H, 6.75; N, 4.50.
Found: C, 73.15; H, 6.83; N, 4.47.
Compound 28cA.
White crystals, mp 91.5ꢂ92 °C (ethyl acetateꢂhexane); Rf 0.47
(ethyl acetateꢂhexane, 1:1); 1H nmr (CDCl3, 400 MHz) ꢀ 1.60 (dd,
1H, J=8.9, 11.8 Hz, H-6endo), 1.68 (s, 3H, Me-2ꢀ), 2.21 (ddd, 1H,
J=3.4, 4.5, 11.8 Hz, H-6exo), 2.39 (dd, 1H, J=4.1, 15.9 Hz, H-3ꢀA),
2.54 (dd, 1H, J=10.0, 15.9 Hz, H-3ꢀB), 2.64 (dd, 1H, J=3.4, 8.9 Hz,
H-5), 3.75 (s, 3H, OMe-4ꢀꢀ), 4.54 (dd, 1H, J=4.1, 10.0 Hz, H-2),
4.80 (brd, 1H, J=0.8 Hz, H-1ꢀA), 4.85 (brd, 1H, J=0.8 Hz, H-1ꢀB),
5.01 (dd, 1H, J=1.7, 4.5 Hz, H-7), 6.34 (dd, 1H, J=1.7, 6.0 Hz, H-
8), 6.47 (d, 1H, J=6.0 Hz, H-9), 6.86 (BBꢀ, 2H, Jꢁ8.9 Hz, H-Ph),
7.29 (AAꢀ, 2H, Jꢁ8.9 Hz, H-Ph); 13C nmr (ꢀDCl3, 100.6 MHz) ꢀ
173.2 (s, ꢀ-4), 157.4 (s, ꢀ-4ꢀꢀ), 140.6 (s, ꢀ-2ꢀ), 136.4 (d, ꢀ-8,
J=175.5 Hz), 132.2 (d, ꢀ-9, J=177.5 Hz), 130.4 (s, ꢀ-1ꢀꢀ), 125.6 (d,
2ꢀ, ꢀ-2ꢀꢀ and 6ꢀꢀ, J=160.5 Hz), 114.1 (d, 2ꢀ, ꢀ-3ꢀꢀ and 5ꢀꢀ, J=160.5
Hz), 113.2 (t, ꢀ-1ꢀ, J=155.5 Hz), 91.6 (s, ꢀ-1), 78.3 (d, ꢀ-7,
J=164.5 Hz), 60.2 (d, ꢀ-2, J=144.8 Hz), 55.2 (q, ꢁꢂꢃ-4ꢀꢀ, J=144.0
Hz), 46.3 (d, ꢀ-5, J=137.7 Hz), 38.0 (t, ꢀ-3ꢀ, J=127.5 Hz), 28.6 (t,
ꢀ-6, J=138.0 Hz), 22.6 (q, ꢂꢃ-2ꢀ, J=126.2 Hz).
2-Methallyl-3-aza-4-oxo-3-(4-methylbenzyl)-10-oxatricyclo-
[5.2.1.01,5]dec-8-ene (28e).
Yield 10.51 g (68%); ratio of isomers A/B = 8.4/1; ir: 1645
(C=C), and 1680 (NꢂC=O) cmꢂ1; ms: m/z M+ 309 (12), 254
(16), 200 (20), 174 (7), 120 (27), 105 (100), 90 (4), 64 (4), 54
(12), 38 (5).
Anal. Calcd. for C20H23NO2: C, 77.67; H, 7.44; N, 4.53.
Found: C, 77.61; H, 7.40; N, 4.34.
Compound 28eA.
White crystals, mp 101.5ꢂ103 °C (ethyl acetateꢂhexane); Rf
1
0.35 (ethyl acetateꢂhexane, 1:1); H nmr (CDCl3, 400 MHz) ꢀ
1.60 (dd, 1H, J=8.8, 11.7 Hz, H-6endo), 1.72 (s, 3H, Me-2ꢀ),
2.24 (ddd, 1H, J=3.3, 4.4, 11.7 Hz, H-6exo), 2.30 (s, 3H, Me-
4ꢀꢀ), 2.37 (dd, 1H, J=8.3, 15.1 Hz, H-3ꢀB), 2.52 (dd, 1H, J=5.7,
15.1 Hz, H-3ꢀA), 2.57 (dd, 1H, J=3.3, 8.8 Hz, H-5), 3.87 (dd,
1H, J=5.7, 8.3 Hz, H-2), 4.00 (d, 1H, J=15.4 Hz, NCH2-B), 4.83
(s, 1H, H-1ꢀA), 4.91 (brs, 1H, H-1ꢀB), 5.03 (dd, 1H, J=1.3, 4.4
Hz, H-7), 5.07 (d, 1H, J=15.4 Hz, NCH2-A), 6.34 (dd, 1H,
J=1.3, 5.9 Hz, H-8), 6.44 (d, 1H, J=5.9 Hz, H-9), 7.10 (s, 4H,
H-Ph).
Compound 28cB.
1
Pale yellow oil, Rf 0.36 (ethyl acetateꢂhexane, 1:1); H nmr
(CDCl3, 400 MHz) ꢀ 1.60 (dd, 1H, J=8.8, 11.8 Hz, H-6endo),
1.69 (s, 3H, Me-2ꢀ), 2.22 (dd, 1H, J=10.2, 13.8 Hz, H-3ꢀB), 2.25
(ddd, 1H, J=3.5, 4.5, 11.8 Hz, H-6exo), 2.27 (dd, 1H, J=4.5, 13.8
Hz, H-3ꢀA), 2.52 (dd, 1H, J=3.5, 8.8 Hz, H-5), 3.76 (s, 3H, OMe-
4ꢀꢀ), 4.67 (dd, 1H, J=4.5, 10.2 Hz, H-2), 4.72 (brs, 1H, H-1ꢀB),
4.78 (m, 1H, H-1ꢀA), 5.07 (dd, 1H, J=1.7, 4.5 Hz, H-7), 6.26 (dd,
1H, J=1.7, 5.8 Hz, H-8), 6.35 (d, 1H, J=5.8 Hz, H-9), 6.89 (BBꢀ,
Compound 28eB.
1
Pale yellow oil, Rf 0.44 (ethyl acetateꢂhexane, 1:1); H nmr
(CDCl3, 400 MHz) ꢀ 1.59 (dd, 1H, J=8.8, 11.8 Hz, H-6endo),
1.59 (s, 3H, Me-2ꢀ), 2.21 (ddd, 1H, J=3.5, 4.6, 11.8 Hz, H-
6exo), 2.32 (s, 3H, Me-4ꢀꢀ), 2.37 (dd, 1H, J=10.2, 13.6 Hz, H-
3ꢀB), 2.40 (dd, 1H, J=3.5, 8.8 Hz, H-5), 2.47 (dd, 1H, J=4.6,
13.6 Hz, H-3ꢀA), 4.03 (d, 1H, J=15.2 Hz, NCH2-B), 4.07 (dd,
1H, J=4.6, 10.2 Hz, H-2), 4.69 (brs, 1H, H-1ꢀB), 4.78 (brs, 1H,
H-1ꢀA), 4.89 (d, 1H, J=15.2 Hz, NCH2-A), 5.03 (dd, 1H, J=0.9,
4.6 Hz, H-7), 6.24 (m, 2H, H-8 and H-9), 7.12 (s, 4H, H-Ph).
1
2H, Jꢁ8.9 Hz, H-Ph), 7.15 (AAꢀ, 2H, Jꢁ8.9 Hz, H-Ph); H nmr
(ꢀ6D6, 400 MHz) ꢀ 1.35 (dd, 1ꢄ, J6endo,6exo=11.7, J5,6endo=8.7 Hz,
ꢄ-6endo), 1.71 (s, 3ꢄ, ꢂꢃ-2ꢀ), 2.31 (dd, 1ꢄ, J5,6endo=8.7,
J5,6exo=3.5 Hz, ꢄ-5), 2.42 (ddd, 1ꢄ, J6endo,6exo=11.8, J7,6exo=4.5,
J5,6exo=3.5 Hz, ꢄ-6exo), 2.49 (dd, 1ꢄ, J2,3ꢀꢅ=3.6, J3ꢀA,3ꢀ =13.7 Hz,
ꢄ-3ꢀꢅ), 2.62 (dd, 1ꢄ, J2,3ꢀ =10.9, J3ꢀA,3ꢀ =13.7 Hz, ꢄ-3ꢀB), 3.40
(s, 3ꢄ, ꢁꢂꢃ-4ꢀꢀ), 4.45 (dd, 1ꢄ, J2,3ꢀ =10.9, J2,3ꢀꢅ=3.6 Hz, ꢄ-2),

1492
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
2-Methallyl-3-aza-4-oxo-3-(4-methoxybenzyl)-10-oxatricyclo-
[5.2.1.01,5]dec-8-ene (28f).
J
6exo,7=4.4, J6exo,5=3.0 Hz, H-6exo), 1.83 (s, 3H, Me-2ꢁ), 1.97
(dddd, 1H, J4ax,5=10.5, J4eqv,5=6.6, J6endo,5=7.5, J6exo,5=3.0 Hz, H-
5endo), 2.09 (dd, 1H, J4eqv,4ax=8.5, J4ax,5=10.5 Hz, H-4ax), 2.43
(dd, 1H, J ꢄ=15.3, J2,3ꢁ =5.8 Hz, ꢁ-3ꢁA), 2.48 (dd, 1H,
White crystals, yield 14.14 g (87%); ratio of isomers A/B =
4.5/1 (inseparable mixture of isomers); mp 57.5ꢀ64 °C (ethyl
acetateꢀhexane); Rf 0.25 (ethyl acetateꢀhexane, 1:3); ir: 1640
(C=C), and 1675 (NꢀC=O) cmꢀ1; ms: m/z M+ 325 (24), 270 (6),
,
J
ꢄ=15.3, J2,3ꢁꢄ=8.1 Hz, H-3ꢁB), 3.11 (dd, 1H, J4eqv,4ax=8.5,
,
J4eqv,5=6.6 Hz, H-4eqv), 3.11 (dd, 1H, J2,3ꢁꢄ=8.1, J2,3ꢁA=5.8 Hz, H-
2), 3.47 (d, 1H, J ꢄ=12.8 Hz, NCH2-B), 4.05 (d, 1H, J ꢄ=12.8
Hz, NCH2-A), 4.88 (s, 1H, H-1ꢁA), 4.91 (s, 1H, H-1ꢁB), 4.98
(dd, 1H, J7,6exo=4.4, J8,7=1.7 Hz, H-7), 6.23 (dd, 1H, J8,9=5.9,
J8,7=1.7 Hz, H-8), 6.43 (d, 1H, J8,9=5.9 Hz, H-9), 7.24ꢀ7.33 (m,
5H, H-Ph).
1
,
,
217 (6), 136 (21), 121 (100), 91 (4), 77 (7), 55 (18), 39 (4); H
nmr (CDCl3, 400 MHz, isomer A) ꢀ 1.60 (dd, 1H, J=8.9, 11.7 Hz,
H-6endo), 1.71 (s, 3H, Me-2ꢁ), 2.23 (ddd, 1H, J=3.5, 4.5, 11.7 Hz,
H-6exo), 2.36 (dd, 1H, J=8.3, 15.2 Hz, H-3ꢁB), 2.51 (dd, 1H,
J=5.7, 15.2 Hz, H-3ꢁA), 2.56 (brdd, 1H, J=3.5, 8.9 Hz, H-5), 3.76
(s, 3H, OMe-4ꢁꢁ), 3.87 (dd, 1H, J=5.7, 8.3 Hz, H-2), 3.98 (d, 1H,
J=15.4 Hz, NCH2-B), 4.82 (brs, 1H, H-1ꢁA), 4.90 (brs, 1H, H-
1ꢁB), 5.02 (dd, 1H, J=1.7, 4.5 Hz, H-7), 5.04 (d, 1H, J=15.4 Hz,
NCH2-A), 6.33 (dd, 1H, J=1.7, 5.9 Hz, H-8), 6.43 (d, 1H, J=5.9
Hz, H-9), 6.83 (BBꢁ, 2H, H-Ph), 7.12 (AAꢁ, 2H, H-Ph).
Anal. Calcd. for C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found:
C, 81.23; H, 8.39; N, 5.11.
Compound 30.
Colourless oil, yield 10% (1.01 g); Rf 0.78 (ethyl
acetateꢀhexane, 1:100); ir: 1645 (ꢀ=ꢀ) cmꢀ1; ms: m/z [Mꢀ55]+
226 (100), 131 (3), 91 (64), 68 (3), 41 (4); H nmr (CDCl3, 400
Anal. Calcd. for C20H23NO3: C, 73.85; H, 7.08; N, 4.31.
Found: C, 73.75; H, 7.12; N, 4.30.
1
MHz) ꢀ 1.64 (brs, 3H, ꢂꢃ-2), 2.55 (dd, 1H, J ꢄ=14.1, J3ꢄ,4=7.7
,
4-N-Phenylamino-N-acryloyl-4-(2-furyl)butene-1 (27a).
Hz, H-3B), 2.67 (ddd, 1H, J ꢄ=14.1, J3A,4=7.7, J3A,1=0.7 Hz, H-
,
3A), 2.80 (dd, 1H, J3ꢁA,3ꢁꢄ=14.2, J ,2ꢁ=8.0 Hz, H-3ꢁB), 3.19 (d,
ꢄ
3ꢁ
Was isolated along with 28a (see Scheme 6). White crystals,
yield 3.51 g (25%); mp 65.5ꢀ66.5 °ꢀ (ethyl acetateꢀhexane);
Rf 0.68 (ethyl acetateꢀhexane, 1 : 3); ir: 1645 (NꢀC=O and
ꢀ=ꢀ) cmꢀ1; ms: m/z M+ 281 (13), 238 (3), 226 (44), 172 (100),
161 (2), 148 (3), 135 (18), 117 (10), 107 (3), 91 (8), 77 (13),
1H, J ꢄ=13.9 Hz, NCH2Ph-B), 3.29 (ddt, 1H, J3ꢁA,3ꢁꢄ=14.2,
,
J3ꢁA,2ꢁ=4.7, J3ꢁA,1ꢁ=1.6 Hz, H-3ꢁA), 4.05 (t, 1H, J4,3=7.7 Hz, H-4),
3.92 (d, 1H, J ꢄ=13.9 Hz, NCH2Ph-A), 4.69 (dq, 1H, J1,1=1.0,
,
J1trans,ꢂꢃ=2.0 Hz, H-1trans), 4.76 (brs, 1H, J1,1=1.0 Hz, H-1cis),
5.12 (ddd, 1H, J2ꢁ,1ꢁcis=10.2, J1ꢁcis,3ꢁ =1.6, J1ꢁ,1ꢁ=0.9 Hz, H-1ꢁcis),
5.12 (ddd, 1H, J2ꢁ,1ꢁtrans=17.3, J1ꢁtrans,3ꢁ =1.6, J1ꢁ,1ꢁ=0.9 Hz, H-
1ꢁtrans), 5.81 (dddd, 1H, J2ꢁ,1ꢁtrans=17.3, J2ꢁ,1ꢁcis=10.2, J2ꢁ,3ꢁꢄ=8.0,
J2ꢁ,3ꢁA=4.7 Hz, H-2ꢁ), 6.15 (dd, 1H, Jꢅ ꢅ =3.1, Jꢆ ꢅ =0.9 Hz, H-ꢅꢁ),
1
65 (2), 55 (23), 39 (3), 27 (4); H nmr (CDCl3, 400 MHz) ꢀ
1.79 (s, 3ꢁ, ꢂꢃ-2), 2.43 (dd, 1ꢁ, J3 ꢄ=14.7, J ,4=8.6 Hz, ꢁ-
ꢄ
3
,3
3ꢄ), 2.54 (dd, 1ꢁ, J3 ꢄ=14.7, J3 ,4=6.7 Hz, ꢁ-3 ), 4.80 (brs,
,3
,
ꢁ
, ꢁ
2ꢁ, ꢁ-1B), 4.85 (brs, 2ꢁ, ꢁ-1A), 5.48 (dd, 1ꢁ, J2ꢁ,1ꢁcis=10.3,
J1ꢁcis,1ꢁtrans=2.0 Hz, ꢁ-1ꢁcis), 5.81 (dd, 1H, J2ꢁ,1ꢁcis=10.3,
J2ꢁ,1ꢁtrans=16.8 Hz, H-2ꢁ), 6.08 (brd, 1ꢁ, Jꢅ ꢅ =3.2 Hz, ꢁ-ꢅꢁ), 6.25
6.36 (dd, 1H, Jꢅ ꢅ =3.1, Jꢆ ꢅ=1.8 Hz, H-ꢅ), 7.22ꢀ7.39 (m, 5H, H-
,
ꢁ
,
Ph), 7.42 (dd, 1H, Jꢆ ꢅ=1.8, Jꢆ ꢅ =0.9 Hz, H-ꢆ).
,
, ꢁ
,
ꢁ
Anal. Calcd. for C19H23NO: C, 81.10; H, 8.24; N, 4.98. Found:
C, 81.20; H, 8.21; N, 4.99.
(dd, 1ꢁ, Jꢅ ꢅ =3.2, Jꢆ ꢅ=1.7 Hz, ꢁ-ꢅ), 6.39 (dd, 1ꢁ,
,
ꢁ
,
J1ꢁcis,1ꢁtrans=2.0, J1ꢁtrans,2ꢁ=16.8 Hz, ꢁ-1ꢁtrans), 6.43 (dd, 1ꢁ,
J4,3 =6.7, J4,3ꢄ=8.6 Hz, ꢁ-4), 7.20ꢀ7.32 (m, 5ꢁ, ꢁ-Ph), 7.37
(dd, 1ꢁ, Jꢆ ꢅ=1.7, Jꢆ ꢅ =0.7 Hz, ꢁ-ꢆ).
2-Methallyl-3-aza-3-phenyl-10-oxatricyclo[5.2.1.01,5]dec-8-en (31).
,
, ꢁ
Sodium iodide dihydrate (7.66 g, 0.041 mol) was added to a
solution of allylbromide (3.5 mL, 0.04 mol) in 60 mL of acetone
and the reaction mixture was stirred for 1 h at 22 °C. Then
potash (7.33 g, 0.053 mol) and amine 11a (3.0 g, 0.013 mol)
were added and the reaction mass was refluxed for 18 h until the
disappearance of the starting material spot (TLC control). The
inorganic precipitate was filtered off and washed with acetone (2
ꢂ 50 mL). The residue obtained after acetone evaporation was
purified by column chromatography on Al2O3 (4.5 ꢂ 30 cm,
using hexane as eluent).
Anal. Calcd. for C18H19NO2: C, 76.84; H, 6.81; N, 4.98.
Found: C, 76.79; H, 6.75; N, 4.90.
Compounds 9A and 9B were synthesized earlier [3].
2-Methallyl-3-aza-3-benzyl-10-oxatricyclo[5.2.1.01,5]dec-8-en
(29) and N-Allyl-2-methyl-4-N-benzylamino-4-(2ꢁ-furyl)but-1-
en (30).
Potash (7.38 g, 0.054 mol) and allylbromide (3.72 mL, 0.043
mol) were added to a solution of amine 12a (8.59 g, 0.036 mol)
in 80 mL of acetone. The reaction mixture was refluxed for 3 h
(TLC monitoring). Inorganic precipitate was filtered off and
washed with acetone (2 ꢂ 60 mL). The residue obtained after
acetone evaporation was refluxed in toluene (50 mL) for 4 h
(TLC monitoring). Toluene was removed in vacuo, products 29,
30 were separated by column chromatography on Al2O3 (2.5 ꢂ
25 cm, using hexane as eluent). In case of N-allylderivative 30
the eluent was removed under reduced pressure at room
temperature.
Compound 31.
Viscous yellow oil; yield 48% (1.67 g); ratio of isomers 10/1;
Rf 0.41 (ethyl acetateꢀhexane, 1:50); ir: 1640 (ꢀ=ꢀ) cmꢀ1; ms:
m/z M+ 267 (18), 212 (100), 171 (16), 144 (10), 115 (7), 104
1
(34), 91 (11), 77 (49), 65 (9), 51 (20), 39 (29); H nmr (CDCl3,
400 MHz) ꢀ 1.55 (dd, 1H, J6exo,6endo=11.5, J6endo,5=7.5 Hz, H-
6endo), 1.90 (ddd, 1H, J6exo,6endo=11.5, J6exo,7=4.5, J6exo,5=2.5 Hz,
H-6exo), 1.90 (s, 3H, ꢂꢃ-2ꢁ), 2.25 (dd, 1H, J ꢄ =17.3,
ꢁ,
ꢁ
J2,3ꢁꢄ=10.8 Hz, H-3ꢁB), 2.34 (ddt, 1H, J4ax,5=J4eqv,5=8.7,
Compound 29.
J6endo,5=7.5, J6exo,5=2.5 Hz, H-5endo), 2.69 (brdd, 1H, J ꢄ =17.3,
ꢁ,
ꢁ
Colourless viscous oil; yield 46% (4.65 g); Rf 0.37 (ethyl
acetateꢀhexane, 1:100); ir: 1640 (ꢀ=ꢀ) cmꢀ1; ms: m/z [Mꢀ55]+
226 (93), 131 (3), 117 (2), 91 (100), 81 (3), 65 (6), 41 (9), 28
(4); H nmr (CDCl3, 400 MHz) ꢀ 1.28 (dd, 1H, J6exo,6endo=11.4,
J6endo,5=7.5 Hz, H-6endo), 1.67 (ddd, 1H, J6exo,6endo=11.4,
J2,3ꢁ =1.8 Hz, ꢁ-3ꢁ ), 2.92 (t, 1H, J4eqv,4ax=J4ax,5=8.7 Hz, H-4ax),
3.87 (t, 1H, J4eqv,4ax=J4eqv,5=8.7 Hz, H-4eqv), 4.24 (dd, 1H,
J2,3ꢁꢄ=10.8, J2,3ꢁA=1.8 Hz, H-2), 4.94 (brs, 1H, H-1ꢁA), 5.00 (brs,
1H, H-1ꢁB), 5.03 (dd, 1H, J7,6exo=4.5, J8,7=1.7 Hz, H-7), 6.38 (dd,
1H, J8,9=5.9, J8,7=1.7 Hz, H-8), 6.50 (d, 1H, J8,9=5.9 Hz, H-9),
1

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1493
Furfurylsubstituted Homoallylamines to Allylhalides
6.59 (d, 2H, Jm,o=7.8 Hz, ꢀ-Phortho), 6.70 (t, 1H, Jm,p=7.3 Hz,
ꢀ-Phpara), 7.25 (dd, 2H, Jm,o=7.8, Jm,p=7.3 Hz, ꢀ-Phmetha).
Anal. Calcd. for C18H21NO: C, 81.86; H, 7.92; N, 5.24. Found:
C, 81.81; H, 7.94; N, 5.33.
White crystals, yield 1.87 g (64%); mp 146.5ꢀ148 °ꢁ
(hexaneꢀethyl acetate); Rf 0.67 (ethyl acetateꢀhexane, 1:1); ir:
1680 (NꢀC=O) cmꢀ1; ms: m/z M+ 293 (72), 278 (100), 263 (20),
248 (6), 235 (10), 220 (5), 207 (8), 191 (4), 146 (3), 131 (3), 115
1
(3), 103 (5), 89 (4), 77 (8), 63 (3), 51 (2); H nmr (CDCl3, 400
Isoindolo[2,1-a]quinolines 32aꢀc and Isoindolo[2,1-b][2]benz-
azepines 33aꢀc, 34b,c.
MHz) ꢀ 1.40 (s, 3H, Me-5), 1.48 (s, 3H, Me-5), 1.62 (dd, 1H,
J=12.9, 13.3 Hz, H-6ax), 2.28 (dd, 1H, J=2.6, 13.3 Hz, H-6eq),
3.83 (s, 3H, OMe-3), 4.79 (dd, 1H, J=2.6, 12.9 Hz, H-6a), 6.86
(dd, 1H, J=2.9, 9.0 Hz, H-2), 6.94 (d, 1H, J=2.9 Hz, H-4),
7.48ꢀ7.51 (m, 2H, H-7 and H-9), 7.59 (dt, 1H, J=1.2, 7.9 Hz, H-
8), 7.92 (dd, 1H, J=1.2, 7.9 Hz, H-10), 8.43 (d, 1H, J=9.0 Hz,
H-1).
Typical Procedure.
A mixture of corresponding adduct 28 (0.01 mol) and 30 mL
of PPA was stirred for 1ꢀ2 h (TLC monitoring) at 90ꢀ110 °C
(TLC monitoring). At the end of the reaction, the mixture was
cooled and diluted with water (100 mL). After that four 60-mL
extractions with chloroform were performed. The organic layers
were combined, dried (MgSO4) and concentrated. The resulting
residue was purified by chromatography on Al2O3 (2.5 ꢁ 20 cm,
using hexane/ethyl acetate, 5:1 as eluent) to obtain the products
32aꢀc, 33a as white crystals. In case of adduct 28e cyclization
the obtained isomeric mixture (33b/34b = 1/3) was three times
recrystallized (hexaneꢀethyl acetate) to isolate the desired
product 34b. The mother solution contained the isomeric
mixture 33b/34b in ratio 1/3.5.
Anal. Calcd. for C19H19NO2: C, 77.82; H, 6.48; N, 4.78.
Found: C, 77.78; H, 6.45; N, 4.79.
13,13-Dimethyl-7-oxo-5,11b,12,13-tetrahydro-7H-isoindolo-
[2,1-b][2]benzazepine (33a).
White crystals, yield 1.69 g (61%); mp 106.5ꢀ108.5 °ꢁ
(hexaneꢀethyl acetate); Rf 0.46 (ethyl acetateꢀhexane, 1:1); ir:
1680 (NꢀC=O) cmꢀ1; ms: m/z M+ 277 (100), 262 (22), 234 (23),
221 (11), 193 (6), 145 (17), 132 (24), 129 (15), 115 (10), 103
1
(5), 91 (18), 77 (5); H nmr (CDCl3, 400 MHz) ꢀ 1.54 (s, 3H,
Me-13), 1.61 (s, 3H, Me-13), 1.59 (dd, 1H, J12ax,12eqv=14.1,
J11b,12ax=12.0 Hz, H-12ax), 2.27 (dd, 1H, J12ax,12eqv=14.1,
5,5-Dimethyl-5,6,6a,11-tetrahydro-11-oxoisoindolo[2,1-a]quin-
oline (32a).
J11b,12eqv=3.2 Hz, H-12eqv), 4.70 (d, 1H, Jꢅ =15.5 Hz, H-5B),
,
White crystals, yield 1.60 g (61%); mp 118ꢀ119 °ꢁ
(hexaneꢀethyl acetate); Rf 0.66 (ethyl acetateꢀhexane, 2:1); ir:
1675 (NꢀC=O) cmꢀ1; ms: m/z M+ 263 (47), 248 (100), 232 (13),
222 (5), 204 (7), 115 (11), 91 (7), 77 (8), 39 (3); 1H nmr (CDCl3,
400 MHz) ꢀ 1.41 (s, 3H, Me-5), 1.49 (s, 3H, Me-5), 1.63 (dd,
1H, J=12.9, 13.1 Hz, H-6ax), 2.29 (dd, 1H, J=2.7, 13.1 Hz, H-
6eq), 4.81 (dd, 1H, J=2.7, 12.9 Hz, H-6a), 7.14 (dt, 1H, J=1.3,
7.5 Hz, H-3), 7.29 (dt, 1H, J=1.5, 7.5 Hz, H-2), 7.41 (dd, 1H,
J=1.5, 7.6 Hz, H-4), 7.48ꢀ7.52 (m, 2H, H-7 and H-9), 7.60 (dt,
1H, J=1.2, 7.4 Hz, H-8), 7.94 (dd, 1H, J=1.2, 8.3 Hz, H-10),
8.50 (dt, 1H, J=1.3, 7.5 Hz, H-1); 13C nmr (ꢁDCl3, 100.6 MHz)
ꢀ 165.6 (C=O), 144.4 (s), 134.9 (s), 134.5 (s), 132.5 (s), 131.8
(d), 128.2 (d), 126.6 (d), 126.5 (d), 124.0 (d), 123.9 (d), 121.6
(d), 120.3 (d), 55.4 (d, ꢁ-6ꢂ), 43.4 (t, ꢁ-6), 33.4 (s, ꢁ-5), 32.1 (q,
ꢃꢄ-5), 30.8 (q, ꢃꢄ-5).
4.91 (dd, 1H, J11b,12ax=12.0, J11b,12eqv=3.2 Hz, H-11b), 5.32 (d, 1H,
Jꢅ =15.5 Hz, H-5A), 7.19 (dt, 1H, J9,10=J8,9=7.7, J9,11=1.0 Hz,
,
H-9), 7.24 (dd, 1H, J10,11=7.7, J9,11=1.5 Hz, H-11), 7.37ꢀ7.43 (m,
4H), 7.51 (dt, 1H, J9,10=J10,11=7.7, J8,10=1.0 Hz, H-10), 7.82 (d,
1H, J8,9=8.1 Hz, H-8).
Anal. Calcd. for C19H19NO: C, 82.31; H, 6.86; N, 5.05. Found:
C, 82.27; H, 6.81; N, 5.15.
2,13,13-Trimethyl-7-oxo-5,11b,12,13-tetrahydro-7H-isoindolo-
[2,1-b][2]benzazepine (33b) and 3,13,13-Trimethyl-7-oxo-5,
11b,12,13-tetrahydro-7H-isoindolo[2,1-b][2]benzazepine (34b).
Total yield of the isomers mixture 0.76 g (26%). Ratio of
isomers 33b/34b = 1/3.
Compound 33b.
1
Was isolated along with 34b. H nmr (CDCl3, 400 MHz) ꢀ
Anal. Calcd. for C18H17NO: C, 82.13; H, 6.46; N, 5.32. Found:
C, 82.20; H, 6.48; N, 5.39.
1.52 (s, 3H, ꢃꢄ-13), 1.56 (dd, 1H, J12ax,12eqv=14.1, J11b,12ax=12.0
Hz, H-12ax), 1.58 (s, 3H, ꢃꢄ-13), 2.24 (dd, 1H, J12ax,12eqv=14.1,
J11b,12eqv=3.2 Hz, H-12eqv), 2.30 (s, 3H, ꢃꢄ-2), 4.62 (d, 1H,
3,5,5-Trimethyl-5,6,6a,11-tetrahydro-11-oxoisoindolo[2,1-a]-
quinoline (32b).
Jꢅ =15.5 Hz, H-5B), 4.87 (dd, 1H, J11b,12ax=12.0, J11b,12eqv=3.2
,
Hz, H-11b), 5.27 (d, 1H, Jꢅ =15.5 Hz, H-5A), 6.98 (dd, 1H,
,
White crystals, yield 1.94 g (70%); mp 187.5ꢀ189 °ꢁ
(hexaneꢀethyl acetate); Rf 0.58 (ethyl acetateꢀhexane, 3:1); ir:
1685 (NꢀC=O) cmꢀ1; ms: m/z M+ 277 (54), 262 (100), 247 (21),
J3,4=7.6, J1,3=1.5 Hz, H-3), 7.17 (d, 1H, J1,3=1.5 Hz, H-1), 7.28
(d, 1H, J4,3=7.6 Hz, H-4), 7.39 (d, 1H, J10,11=7.5 Hz, H-11), 7.39
(t, 1H, J8,9=J10,9=7.5 Hz, H-9), 7.49 (dt, 1H, J10,9=J10,11=7.5,
J8,10=1.5 Hz, H-10), 7.78 (dd, 1H, J8,9=7.5, J8,10=1.5 Hz, H-8);
13C nmr (ꢁDCl3, 100.6 MHz) ꢀ 166.4 (s, N-C=O), 146.4 (s),
145.7 (s), 137.2 (s), 133.0 (s), 131.8 (s), 131.1 (d), 131.0 (d),
127.9 (d), 127.1 (d), 127.0 (d), 123.6 (d), 121.4 (d), 59.3 (d, C-
11b), 47.1 (t, C-12), 46.1 (t, C-5), 37.5 (s, C-13), 32.6 (q, ꢃꢄ-
13), 25.7 (q, ꢃꢄ-13), 21.2 (q, ꢃꢄ-2).
1
232 (16), 218 (5), 124 (5), 108 (6), 102 (4), 77 (6), 51 (2); H
nmr (CDCl3, 400 MHz) ꢀ 1.40 (s, 3H, Me-5), 1.48 (s, 3H, Me-
5), 1.61 (dd, 1H, J=12.6, 13.2 Hz, H-6ax), 2.28 (dd, 1H, J=1.6,
13.2 Hz, H-6eq), 2.35 (s, 3H, Me-3), 4.79 (dd, 1H, J=1.6, 12.6
Hz, H-6a), 7.10 (dd, 1H, J=1.5, 8.3 Hz, H-2), 7.20 (d, 1H, J=1.5
Hz, H-4), 7.48ꢀ7.52 (m, 2H, H-7 and H-9), 7.58 (dt, 1H, J=1.2,
7.9 Hz, H-8), 7.93 (dd, 1H, J=1.2, 7.9 Hz, H-10), 8.38 (d, 1H,
J=8.3 Hz, H-1).
Compound 34b.
Anal. Calcd. for C19H19NO: C, 82.31; H, 6.86; N, 5.05. Found:
C, 82.29; H, 6.82; N, 5.10.
White crystals, yield 0.38
g (13%); mp 150.5ꢀ152 °ꢁ
(hexaneꢀethyl acetate); Rf 0.57 (ethyl acetateꢀhexane, 1:1); ir: 1675
(NꢀC=O) cmꢀ1; ms: m/z M+ 291 (100), 276 (31), 248 (55), 235 (13),
220 (10), 207 (8), 186 (14), 159 (26), 146 (33), 129 (30), 115 (22),
5,5-Dimethyl-5,6,6a,11-tetrahydro-3-methoxy-11-oxoisoindolo-
[2,1-a]quinoline (32c).

1494
A. V. Varlamov, E. V. Boltukhina, F. I. Zubkov, E. V. Nikitina and K. F. Turchin
Vol 43
105 (29), 91 (14), 77 (19), 63 (5), 51 (5), 41 (4); 1H nmr (CDCl3, 400
MHz) ꢀ 1.50 (s, 3H, ꢀꢁ-13), 1.57 (s, 3H, ꢀꢁ-13), 1.54 (dd, 1H,
J12ax,12eqv=14.1, J11b,12ax=12.0 Hz, H-12ax), 2.24 (dd, 1H,
J12ax,12eqv=14.1, J11b,12eqv=3.2 Hz, H-12eqv), 2.29 (s, 3H, ꢀꢁ-3), 4.64 (d,
(18), 304 (21), 289 (4), 276 (8), 220 (4), 185 (6), 171 (16), 159 (11),
132 (25), 129 (9), 115 (7), 77 (5); 1H nmr (CDCl3, 400 MHz) ꢀ 1.57
(s, 3H, ꢀꢁ-13), 1.63 (s, 3H, ꢀꢁ-13), 1.58 (dd, 1H, J12ax,12eqv=14.2,
J11b,12ax=12.1 Hz, H-12ax), 2.30 (dd, 1H, J12ax,12eqv=14.2, J11b,12eqv=3.1
Hz, H-12eqv), 4.62 (d, 1H, JA,B=14.7 Hz, ClCHAHB), 4.72 (d, 1H,
1H, Jꢂ =15.5 Hz, H-5B), 4.88 (dd, 1H, J11b,12ax=12.0, J11b,12eqv=3.2 Hz,
,
H-11b), 5.25 (d, 1H, Jꢂ =15.5 Hz, H-5A), 7.03 (dd, 1H, J1,2=8.0,
Jꢂ =15.7 Hz, H-5B), 4.73 (d, 1H, JA,B=14.7 Hz, ClCHAHB), 4.94
,
,
J2,4=2.0 Hz, H-2), 7.22 (d, 1H, J2,4=2.0 Hz, H-4), 7.25 (d, 1H,
J1,2=8.0 Hz, H-1), 7.39 (d, 1H, J10,11=7.5 Hz, H-11), 7.39 (t, 1H,
J8,9=J10,9=7.5 Hz, H-9), 7.49 (dt, 1H, J10,9=J10,11=7.5, J8,10=1.5 Hz, H-
10), 7.78 (dd, 1H, J8,9=7.5, J8,10=1.5 Hz, H-8); 13C nmr (ꢃDCl3, 100.6
MHz) ꢀ 166.4 (s, NCO), 145.7 (s), 143.6 (s), 136.0 (s), 135.8 (s),
131.7 (s), 131.7 (d, ꢃ-4, J=155.5 Hz), 131.0 (d, C-10, J=161.0 Hz),
128.1 (d, C-2, J=155.5 Hz), 127.8 (d, C-9, J=161.5 Hz), 126.1 (d, C-
1, J=155.0 Hz), 123.5 (d, C-8, J=164.0 Hz), 121.4 (d, ꢃ-7, J=161.0
Hz), 59.3 (d, C-11b, J=141.0 Hz), 47.1 (t, C-12, J=128.5 Hz), 46.3 (t,
C-5, J=137.0 Hz), 37.2 (s, C-13), 32.6 (q, ꢀꢁ-13, J=127.0 Hz), 25.6
(q, ꢀꢁ-13, J=126.0 Hz), 20.3 (q, ꢀꢁ-3, J=126.5 Hz).
(dd, 1H, J11b,12ax=12.1, J11b,12eqv=3.1 Hz, H-11b), 5.40 (d, 1H,
Jꢂ =15.7 Hz, H-5A), 7.42 (dd, 1H, J10,11=7.5, J9,11=1.1 Hz, H-11),
,
7.43 (dt, 1H, J9,11=1.1, J9,10=J8,9=7.5 Hz, H-9), 7.51 (dd, 1H,
J8,10=1.1, J8,9=7.5 Hz, H-8), 7.53 (dt, 1H, J8,10=1.1, J9,10=J10,11=7.5
Hz, H-10), 7.80 (d, 1H, J1,2=8.3 Hz, H-1), 7.83 (dd, 1H, J1,2=8.3,
J2,4=2.0 Hz, H-2), 7.97 (d, 1H, J2,4=2.0 Hz, H-4).
Anal. Calcd. for C21H20NO2Cl: C, 71.28; H, 5.70; N, 3.96; Cl,
10.02. Found: C, 71.17; H, 5.68; N, 4.03; Hal, 9.83.
3-Nitro-13,13-dimethyl-7-oxo-5,11b,12,13-tetrahydro-7H-isoin-
dolo[2,1-b][2]benzazepine (36).
Anal. Calcd. for C20H21NO: C, 82.47; H, 7.22; N, 4.81. Found:
C, 82.40; H, 6.99; N, 4.89.
Potassium nitrate 0.37 g (3.63 mmol) was added portion wise to
a stirred solution of 33a 1.00 g (3.60 mmol) in 15 mL of conc.
sulfuric acid at ꢀ10 °C. Then the reaction mixture was stirred at
ꢀ5ꢀ0 °C for 1 h and poured into 50 mL of ice water. The obtained
precipitate was collected by filtration, washed with water to pHꢁ7
and dried in air. Then the crude product was purified by
recrystallization (i-PrOH–DMF) to give the desired nitroderivative
36 as white crystals. Yield 0.85 g (73%); mp 191.5ꢀ192 °ꢃ; Rf
0.71 (ethyl acetateꢀchloroform, 1:1); ir: 1693 (NꢀC=O), 1344
(as.-NO2), and 1512 (s.-NO2) cmꢀ1; ms: m/z M+ 322 (100), 305
(88), 293 (13), 275 (51), 263 (23), 233 (17), 217 (17), 204 (7), 191
(13), 158 (20), 146 (46), 115 (82), 89 (48), 77 (66), 51 (28), 39
13,13-Dimethyl-7-oxo-5,11b,12,13-tetrahydro-2-methoxy-7H-
isoindolo[2,1-b][2]benzazepine (33c) and 13,13-Dimethyl-7-
oxo-5,11b,12,13-tetrahydro-3-methoxy-7H-isoindolo[2,1-b][2]-
benzazepine (34c).
Slow-moving colorless oil, total yield of isomeric mixture
0.92 g (30%). Ratio of isomers 33c/34c = 1/1; Rf 0.60 (ethyl
acetateꢀhexane, 1:1); ir: 1680 (NꢀC=O) cmꢀ1; ms: m/z M+ 307
(100), 292 (20), 264 (57), 251 (15), 236 (5), 220 (4), 204 (4),
186 (32), 175 (27), 161 (30), 145 (20), 131 (20), 121 (35), 115
1
1
(20), 103 (22), 91 (24), 77 (26), 63 (7), 51 (7); H nmr isomer
(35); H nmr (CDCl3, 400 MHz) ꢀ 1.59 (s, 3H, ꢀꢁ-13), 1.64 (s,
mixture spectrum (CDCl3, 400 MHz) ꢀ 1.52 (s, 6H, ꢀꢁ-13),
1.56 (dd, 2H, J=14.1, 12.1 Hz, H-12ax), 1.58 (s, 3H, ꢀꢁ-13),
1.60 (s, 3H, ꢀꢁ-13), 2.25 (dd, 2H, J=14.1, 3.3 Hz, H-12eqv),
3.79 (s, 3H, ꢄꢀꢁ), 3.80 (s, 3H, ꢄꢀꢁ), 4.62 (d, 1H, J=15.5 Hz,
H-5), 4.67 (d, 1H, J=15.5 Hz, H-5), 4.88 (dd, 1H, J=12.1, 3.3
Hz, H-11b), 4.90 (dd, 1H, J=12.1, 3.3 Hz, H-11b), 5.26 (d, 1H,
J=15.5 Hz, H-5), 5.28 (d, 1H, J=15.5 Hz, H-5), 6.69 (dd, 1H,
J=8.7, 2.9 Hz), 6.75 (dd, 1H, J=8.2, 2.5 Hz), 6.96 (d, 1H, J=2.5
Hz), 6.98 (d, 1H, J=2.9 Hz), 7.29 (d, 1H, J=8.7 Hz), 7.34 (d, 1H,
J=8.2 Hz), 7.40ꢀ7.44 (m, 2ꢅ), 7.49ꢀ7.54 (m, 2ꢅ), 7.81 (dd, 2H,
J=7.5, 1.7 Hz).
3H, ꢀꢁ-13), 1.60 (dd, 1H, J12ax,12eqv=14.3, J11b,12ax=12.0 Hz, H-
12ax), 2.33 (dd, 1H, J12ax,12eqv=14.3, J11b,12eqv=3.0 Hz, H-12eqv),
4.74 (d, 1H, Jꢂ =15.8 Hz, H-5A), 4.96 (dd, 1H, J11b,12ax=12.0,
,
J11b,12eqv=3.0 Hz, H-11b), 5.44 (d, 1H, Jꢂ =15.8 Hz, H-5B), 7.43
,
(d, 1H, J10,11=7.3 Hz, H-11), 7.44 (t, 1H, J9,10=J8,9=7.3 Hz, H-9),
7.55 (d, 1H, J8,9=7.3 Hz, H-8), 7.54 (t, 1H, J9,10=J10,11=7.3 Hz, H-
10), 7.82 (d, 1H, J1,2=8.3 Hz, H-1), 8.07 (dd, 1H, J1,2=8.3, J2,4=2.4
Hz, H-2), 8.28 (d, 1H, J2,4=2.0 Hz, H-4).
Anal. Calcd. for C19H18N2O3: C, 70.79; H, 5.63; N, 8.69.
Found: C, 70.72; H, 5.67; N, 8.72.
13,13-Dimethyl-7-oxo-5,13-dihydro-7H-isoindolo[2,1-b][2]-benz-
azepine (37).
Anal. Calcd. for C20H21NO2: C, 78.15; H, 6.89; N, 4.56.
Found: C, 78.25; H, 6.93; N, 4.63.
A mixture of amide 33a 0.5 g (1.81 mmol) and nitrobenzene
(30 mL) was refluxed for 40 h (TLC monitoring). After that the
reaction mixture was concentrated in vacuo and the crude
product was purified by column chromatography on Al2O3 (1.5
ꢂ 18 cm, using hexane/ethyl acetate, 10:1 as eluent). The
obtained yellow oil crystallizes to give the product 37. Beige
3-Chloroacetyl-13,13-dimethyl-7-oxo-5,11b,12,13-tetrahydro-7H-
isoindolo[2,1-b][2]benzazepine (35).
Chloroacetyl chloride (1.73 mL, 0.022 mol) was added to a
stirred suspension of AlCl3 (4.81 g, 0.036 mol) in dry dichloroethane
(60 mL). After 0.5 h stirring at room temperature isoindolo-
benzazepine 33a 2.0 g (7.2 mmol) was added and resulting mass
was stirred for 20 h at 24 °C. Then the reaction mixture was poured
into 100 mL of ice water and basified with 25% aqueous ammonia
solution to pH ꢁ 8ꢀ9. Obtained precipitate was filtered off and
washed with chloroform (3 ꢂ 50 mL). The water phase was
extracted with CHCl3 (3 ꢂ 30 mL). Organic phases were collected,
washed with water (1 ꢂ 40 mL), dried over MgSO4 and
concentrated. The crude product was recrystallized from hexane–
ethyl acetate mixture to give desired chloroacetylderivative 35 as
colorless crystals. Yield 1.78 g (70%); mp 141.5ꢀ143.5 °ꢃ with
decomposition; Rf 0.13 (ethyl acetateꢀhexane, 1 : 2); ir: 1675
(NꢀC=O), and 1700 (C=O) cmꢀ1; ms: m/z M+ 353 (35Cl, 100), 338
crystals, yield 0.21
g (42%); mp 122ꢀ124 °ꢃ (ethyl
acetateꢀhexane); Rf 0.69 (ethyl acetateꢀhexane, 1:1); ir: 1680
(NꢀC=O) cmꢀ1; ms: m/z M+ 275 (18), 260 (100), 245 (11), 232
(26), 202 (4), 130 (17), 102 (11), 77 (4), 39 (4); 1H nmr (CDCl3,
400 MHz) ꢀ 1.74 (s, 6H, ꢀꢁ-13), 5.24 (brs, 2H, H-5), 5.82 (s,
1H, H-12), 7.24 (dt, 1H, J=1.4, 7.4 Hz, H-2), 7.31 (dt, 1H,
J=1.4, 7.4 Hz, H-3), 7.39 (dd, 1H, J=1.4, 7.4 Hz, H-1), 7.41 (dt,
1H, J=1.4, 7.5 Hz, H-9), 7.43 (dd, 1H, J=1.4, 7.4 Hz, H-4), 7.51
(dt, 1H, J=1.4, 7.5 Hz, H-10), 7.60 (dd, 1H, J=1.4, 7.5 Hz, H-
11), 7.81 (dd, 1H, J=1.4, 7.5 Hz, H-11).
Anal. Calcd. for C19H17NO: C, 82.88; H, 6.22; N, 5.09. Found:
C, 82.90; H, 6.14; N, 5.11.

Nov-Dec 2006
Intramolecular [4+2] Cycloaddition of
1495
Furfurylsubstituted Homoallylamines to Allylhalides
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Acknowledgments.
The authors are grateful for the financial support by the Russian
Foundation for Basic Research (grant no. 04-03-32 433).
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