New synthetic approach to substituted isoindolo[2,1-a]quinoline carboxylic acids via intramolecular Diels-Alder reaction of 4-(N-furyl-2)-4- arylaminobutenes-1 with maleic anhydride

Article abstract of DOI:10.1016/j.tet.2005.02.017

Acylation of substituted 4-(furyl-2)-4-arylaminobut-1-enes with maleic anhydride provided 2-allyl-6-carboxy-4-oxo-3-aza-10-oxatricyclo[5.2.1.0 ^1,5]dec-8-enes in high yield under mild reaction conditions. The Diels-Alder adducts are formed via an initial amide formation followed by a stereoselective intramolecular [4+2] exo-cycloaddition reaction. Treatment of the tricyclic compounds with phosphoric acid at high temperatures (70-120°C) promoted cyclic ether opening, intramolecular cyclization and aromatization to give the corresponding tetracyclic compounds, 5,6,6a,11-tetrahydro-10- carboxyisoindolo[2,1-a]quinolines, in moderate yields. The influence of the acid and the reaction temperature on the cyclization reactions are also discussed.

Full text of DOI:10.1016/j.tet.2005.02.017

Tetrahedron 61 (2005) 4099–4113
New synthetic approach to substituted isoindolo[2,1-a]quinoline
carboxylic acids via intramolecular Diels–Alder reaction of
4-(N-furyl-2)-4-arylaminobutenes-1 with maleic anhydride
a
b
a
Fedor I. Zubkov,a, Ekaterina V. Boltukhina, Konstantin F. Turchin, Roman S. Borisov
*
and Alexey V. Varlamova
aOrganic Chemistry Department, Russian Peoples Friendship University, 6 Miklukho-Maklayia St., 117198 Moscow, Russian Federation
bCenter of Drugs Chemistry, All-Russian Institute for Chemical and Pharmaceutical Research, 7 Zubovskaya St.,
119815 Moscow, Russian Federation
Received 18 October 2004; revised 24 January 2005; accepted 10 February 2005
Available online 16 March 2005
Abstract—Acylation of substituted 4-(furyl-2)-4-arylaminobut-1-enes with maleic anhydride provided 2-allyl-6-carboxy-4-oxo-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-enes in high yield under mild reaction conditions. The Diels–Alder adducts are formed via an initial amide
formation followed by a stereoselective intramolecular [4C2] exo-cycloaddition reaction. Treatment of the tricyclic compounds with
phosphoric acid at high temperatures (70–120 8C) promoted cyclic ether opening, intramolecular cyclization and aromatization to give the
corresponding tetracyclic compounds, 5,6,6a,11-tetrahydro-10-carboxyisoindolo[2,1-a]quinolines, in moderate yields. The influence of the
acid and the reaction temperature on the cyclization reactions are also discussed.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
cores, several synthetic approaches have been reported1–11
and reviewed.8 Phthalimides,1,11 derivatives of
anthranilic acid,2,4,6,10 benzanilide3 and quinoline deriva-
tives5,7 have been used to prepare isoindolo[2,1-a]quinoline
cores.
Polycyclic nitrogen heterocycles with an isoindolo[2,1-a]-
quinoline motif (1) have been shown to possess important
biological properties. For example, compounds 2 and 3
(Scheme 1), analogs of berberine alkaloids, have been
shown to have effect against N2-induced hypoxia and inhibit
human topoisomerase II, respectively.1,2
Most of these approaches were reported in the last 10 years.
One of the earliest and shortest routes7 for the preparation of
the nitro substituted isoindolo[2,1-a]quinoline was the
interaction between quinoline salt and picryl chloride in
the presence of a base.
Considering the important pharmacological properties
displayed by compounds with isoindolo[2,1-a]quinoline
Scheme 1.
Keywords: Homoallylamines (4-(furyl-2)-4-N-arylaminobut-1-enes); Intramolecular furan Diels–Alder reaction (IMDAF); Isoindolo[2,1-a]quinolines; 3-Aza-
10-oxatricyclo[5.2.1.01,5]decenes; Intramolecular Friedel–Crafts alkylation.
*
Corresponding author. Tel.: C7 95 3355798; fax: C7 95 9550779; e-mail: fzubkov@sci.pfu.edu.ru
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.02.017

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F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
Scheme 2.
As part of our research program directed towards the
preparation of polycyclic nitrogen heterocycles using
homoallylamines as starting compounds, we were interested
in developing a route to isoindolo[2,1-a]quinoline via an
intramolecular Diels–Alder cycloaddition/cyclic ether
opening–aromatization/cyclization sequence. Herein we
disclose our initial results on this study.
Acylation of the secondary amine would be expected to
avoid decomposition of the furan ring under acidic
conditions and to yield the desired cyclized product.
To study the influence of the acetyl group on the cyclization
reaction, amide 4 was chosen as the substrate (Scheme 2). It
was then subjected to various reaction conditions to promote
the intramolecular cyclization reaction. Heating the amide 4
with BF3$OEt2 in ether or AlCl3 in boiling hexane promoted
polymerization and no tetrahydroquinoline 5 formation was
observed. Heating compound 4 in 85% ortho-phosphoric
acid at 30 8C promoted decomposition of amide 4 and
provided N-acetyltoluidine 6, alcohol 7 and diol 8 as the
fragmentation products. N-Acetyltoluidine 6 and the
hydration product 7 were isolated from the reaction mixture;
the formation of compound 8 was confirmed by LCMS. We
would like to note that isolation of N-alkyl substituted
acetanilide as the fragmentation product under harsh
conditions has been described in the previous publication.13
We recently reported the preparation of 1,2,3,4-tetrahydro-
quinolines12 from 4-alkyl- and 4-pyridylsubstituted 4-(N-
aryl)aminobut-1-enes via an acid promoted intramolecular
cyclization. It was established that Friedel–Crafts alkylation
proceeded only under strong mineral acids (H3PO4 or
H2SO4) treatment at 65–85 8C. An initial attempt to utilize
this route to prepare 2-furyl substituted tetrahydroquino-
lines, a potential precursor to isoindolo[2,1-a]quinolines 1,
from 4-(20-furyl)-4-(N-aryl)aminobut-1-enes failed due to
the acid lability of the furfuryl moiety and the deactivating
influence of the ammonium cation formed upon protonation.
Scheme 3.
Scheme 4.

F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
4101
It is also known that under acidic conditions (H3PO4 or
H2SO4, 65–85 8C) 3a,6-epoxyisoindolones 9 undergoes
cyclic ether opening and aromatization reaction sequence
to give isoindolones 10 (Scheme 3).14
derivative 11g required longer reaction time (O7 days) to
drive the reaction to complete (Scheme 5).
The cycloaddition reaction was highly stereoselective and
only the exo-adducts 13, 14 were formed as confirmed by
1
the H NMR spectra of the crude reaction mixtures (in the
In this paper an alternative way of synthesizing tetracycles 1
from homoallylamines based on the acid catalyzed
3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-enes15 cyclization is
presented.
case of endo-orientation of carboxyl group in the 6-position
in the tricycles 13, 14 J6-exo,7 would be around 5.0 Hz).14b
The possible formation of cycloaddition products 16 has
been proposed in the literature.24 The preparation of
monoesters 15, from adducts 14a,b unambiguously con-
firms that no intermediate anhydride 16 was isolated
(Scheme 5).
2. Results and discussion
The required precursors for our study 11a–i and 12a–e were
readily synthesized via a two-step process.16 Condensation
of the aniline and furfural gave the imine, which was then
treated with the Grignard reagent to give amines 11, 12 in
moderate to good yields (Scheme 4).
Exo-3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-enes 13 and 14
were isolated as mixtures of isomers (A and B) based on the
orientation of the methallyl (for 13) or allyl (for 14) groups
relative to the 1,7-epoxy-bridge (Scheme 6). The isomer
ratio varied from 2.5:1 to 1:3 depending on the position and
nature of the substituent. Isomers of compounds 13 and 14
could not be separated due to poor solubility in commonly
used organic solvents (chloroform, alcohol, ethyl acetate).
However, we were able to separate isomers of compound
14d using fractional crystallization from i-PrOH–DMF.
The reaction of homoallylamines 11a–i, 12a–e with maleic
anhydride14a,b,17–23 was carried out at room temperature
(2–4 days) and the products 13 and 14 were isolated in high
yields. In the case of amines with an ortho-substituent
(11b,d,e,h and 12b,c,e) the reaction rate was slow (3–4
days) compared to the unsubstituted amines. The 2-benzyl
Scheme 5.
Scheme 6.

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F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
Scheme 7.
The relative configuration of the isomers 14dA and 14dB
was established basing on 1H NMR NOE values indicating
the increase of Hi intensity when the Hj signal was saturated
(hHi{Hj}). The comparison of the NOE values for 2-H, 5-H,
fast and the reaction proceeded even at 10 8C in the presence
of ortho-phosphoric acid. The products—6b,9-epoxyiso-
indolo[2,1-a]quinolines 20a,b were isolated in 37 and 63%
yields, respectively (Scheme 7).
and 20-H in two isomers of 14d (h5-H{20-H}, h3 -H{5-H}z
0
According to NMR spectroscopic data, the crude product
20a exists in the form of two isomers with relative ratio
w93:7. In the predominant isomer 20a (isolated by
recrystallization) 6a-H and 10a-H were in the same cis-
orientation as 2-H and 5-H in the isomer 14dB of compound
14d (see above). The conclusion followed from comparison
of the NOE values for 6a-H and 10a-H in this isomer of 20a
(h6a-H{10a-H}Z2.4%, h10a-H{6a-H}Z4%) with the NOE
values for 2-H and 5-H in both isomers of 14d. The
stereochemistry of product 20b was established by analogy
with 20a.
3% in 14dA, and !1% in 14dB; h2-H{5-H}zh5-H{2-H} !
1% in 14dA, and z2.5% in 14dB) demonstrated that the
allyl substituent was cis to 5-H in 14dA, and trans to 5-H in
14dB.
Acylation of furfurylamines 11 and 12 with maleic
anhydride initially gave the maleinamide intermediate 17,
which immediately underwent [4C2] cycloaddition to give
cycloadducts 13 and 14. Treatment of N-acetylallylamines 4
and 18 with maleic anhydride did not produce any of the
addition products 19 even in boiling o-xylene (Scheme 6).
That is why the alternative reaction, when an anhydride
similar to 16 could be initially formed (Scheme 5), is hardly
possible. It is notable that the adducts 13 and 14 did not
undergo thermal exo-endo-isomerisation in boiling xylene
as described for similar compounds types.14b
Heating compounds 13 at 70–85 8C in the presence of
phosphoric acid promoted cyclization, cyclic ether opening
followed by aromatization to give isoindolo[2,1-a]quino-
lines 21a–i in 31–72% yields (Scheme 7). Heating
pentacyclic compounds 20a,b at 65 8C in the presence
of PPA readily initiated the cyclic ether opening and
aromatization reaction sequence to give the isoindolo-
quinolines 21d,c in good yields.
The rate of the intramolecular cyclization of 2-methallyl-
substituted 3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-enes
13c,d (possessing an electron rich aromatic ring) was very
Scheme 8.

F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
4103
Intramolecular cyclization of 2-allylsubstituted 3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-enes 14a–e required more
severe reaction conditions compared to their methallyl
substituted analogs 13 (Scheme 8). It can be explained by
poor stability of the intermediate secondary carbocation
formed by protonation of the allyl fragment, compared to
the tertiary one formed from the methallyl fragment.
Accordingly, heating compounds 14a,b in phosphoric acid
at 65 8C initiated the cyclic ether opening and aromatization
reaction sequence to give 3-allylisoindolones 22a,b.
However heating 3-allylisoindolones 22a–e in the presence
of phosphoric acid at 130–150 8C, polyphosphoric acid or
mixture of H3PO4/H2SO4 (3:1, in volume) at 100–120 8C
promoted cyclization to give compounds 23a–e. The best
results were obtained by using the latter conditions to yield
compounds 23a–e in 31–55%.
controlled by TLC silufol UV254 plates. The separation of
the final products was carried out by column chroma-
tography on Al2O3 (activated, neutral, 50–200 mm) or by
fractional crystallization.
3.1. 4-(20-Furyl)-4-N-arylaminobutenes-1 (11a–i, 12a–e).
Typical procedure
The corresponding aldimine (0.30 mol) was slowly added
drop-wise at reflux to a stirred solution of allylmagnesium
bromide, prepared from allyl bromide (39 mL, 0.45 mol)
and magnesium turnings (22.0 g, 0.90 mol) in ether
(300 mL) (for amines 12), or to a solution of methallyl-
magnesium chloride, prepared from methallyl chloride
(41 mL, 0.45 mol) and magnesium turnings (22.0 g,
0.90 mol) in mixture THF–ether (1:1, 300 mL) (for amines
11). 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 the products 11a–i or 12a–e as colourless oils.
In contrast to the 5,5-dimethylisoindolo[2,1-a]quinolines
21, their 5-monosubstituted homologues 23 are formed as a
mixture of two diastereomeres 23A and 23B according to
the orientation of the hydrogen atoms at the C5 and C6a
positions (Scheme 8). The ratio of the isomers 23A/23B
varies from 3.5:1 to 12:1. Isomer 23A with the 5-methyl
group in a pseudo-equatorial orientation (and with a cis-
orientation of the protons 5-H and 6a-H) predominates in all
cases.
3.1.1. 2-Methyl-4-N-phenylamino-4-(20-furyl)butene-1
(11a). Yield 51.76 g (76%); bp 130–133 8C/3 mmHg; nD25
1
1.5578; IR 3390 (NH), and 1645 (C]C) cmK1; H NMR
The relative stereochemistry of 23A a–e and 23B a–e was
determined based on the J values between protons 5-H and
6-H. Thus, for the major isomer 23A with an axial
orientation of the proton 5-H, the coupling constants were
J5ax,6axZ11.0–13.5 and J5ax,6eqZ5.8–6.6 Hz, while for the
minor isomer 23B with an equatorial orientation of the
proton 5-H, the constants were much smaller: J5eq,6axZ5.8
and J5eq,6eqZ1.2 Hz. In both isomers of the tetracyclic acids
23 and also in their 5,5-dimethylanalogues 20, 21 the proton
6a-H has the axial orientation confirmed by the values
of the spin–spin coupling constants (J6a-ax,6axZ9.7–12.9,
J6a-ax,6eqZ2.0–4.9 Hz).
(CDCl3, 200 MHz) d 1.74 (br s, 3H, Me-2), 2.54 (dd, 1H,
JZ14.0, 8.2 Hz, H-3A), 2.66 (dd, 1H, JZ14.0, 6.1 Hz,
H-3B), 3.95 (br s, 1H, NH), 4.58 (dd, 1H, JZ8.2, 6.1 Hz,
H-4), 4.81 (br s, 1H, H-1A), 4.87 (br s, 1H, H-1B), 6.16 (dd,
1H, 0 JZ3.2, 0.9 Hz, H-30), 6.27 (dd, 1H, JZ3.2, 1.8 Hz,
H-4 ), 6.60 (m, 2H, H-Ph), 6.69 (m, 1H, H-Ph), 7.13 (m, 2H,
H-Ph), 7.33 (dd, 1H, JZ1.8, 0.9 Hz, H-50). Anal. Calcd for
C15H17NO: C, 79.29; H, 7.49; N, 6.17. Found: C, 79.27; H,
7.48; N, 6.16.
3.1.2. 2-Methyl-4-N-(200-methylphenyl)amino-4-(20-
furyl)butene-1 (11b). Yield 47.72 g (66%); bp 131–
134 8C/1.5 mmHg; n2D3 1.5521; IR 3421 (NH), and 1641
1
(C]C) cmK1; H NMR (CDCl3, 400 MHz) d 1.68 (br s,
In conclusion, this work demonstrates a new two-step
approach to 10-carboxy-11-oxa-5,6,6a,11-tetrahydroiso-
indolo[2,1-a]-quinolines from readily available 4-(furyl-2)-
4-N-arylaminobut-1-enes which generates the final products
in up to 60% overall yield.
3H, Me-2), 2.15 (s, 3H, Me-200), 2.60 (dd, 1H, JZ13.9,
8.6 Hz, H-3A), 2.69 (dd, 1H, JZ13.9, 5.4 Hz, H-3B), 3.93
(br s, 1H, NH), 4.58 (dd, 1H, JZ8.6, 5.4 Hz, H-4), 4.85 (br
s, 1H, H-1A), 4.89 (br s, 1H, H-1B), 6.16 (dd, 10H, JZ3.2,
0.8 Hz, H-30), 6.27 (dd, 1H, JZ3.2, 1.8 Hz, H-4 ), 6.53 (d,
1H, JZ7.7 Hz, H-Ph), 6.64 (dt, 1H, JZ7.7, 1.0 Hz, H-Ph),
7.04–7.02 (m, 2H, H-Ph), 7.34 (dd, 1H, JZ1.8, 0.8 Hz,
H-50). Anal. Calcd for C16H19NO: C, 79.67; H, 7.88; N,
5.81. Found: C, 79.65; H, 7.88; N, 5.84.
3. Experimental
All reagents were purchased from Acros Chemical Co. All
solvents were used without further purification. Melting
points were determined using a Fisher–Johns melting point
apparatus and are uncorrected. IR spectra were obtained in
KBr pellets for solids or in thin film for oils. NMR spectra
1H (200 or 400 MHz) and 13C (100.6 MHz) were recorded
for solutions (2–5%) in deuteriochloroform or DMSO-d6 at
30 8C and traces of chloroform (1H NMR d 7.26 ppm)
or DMSO-d5H (1H NMR d 2.49 ppm and 13C NMR
39.43 ppm) were used as the internal standard. Mass spectra
were obtained by electron ionization at 70 eV on a Varian
MAT-112 spectrometer or Finnegan MAT95XL chromato-
mass spectrometer. The purity of the obtained substances
and the composition of the reaction mixtures were
3.1.3. 2-Methyl-4-N-(400-methylphenyl)amino-4-(20-
furyl)butene-1 (11c). Yield 54.23 g (75%); bp 138–
140 8C/2.5 mmHg; n2D2 1.5536; IR 3393 (NH), and 1650
1
(C]C) cmK1; H NMR (CDCl3, 200 MHz) d 1.71 (br s,
3H, Me-2), 2.30 (s, 3H, Me-400), 2.63 (dd, 1H, JZ14.3,
8.1 Hz, H-3A), 2.74 (dd, 1H, JZ14.3, 6.1, H-3B), 3.90 (br s,
1H, NH), 4.64 (dd, 1H, JZ8.1, 6.1 Hz, H-4), 4.89 (br s, 1H,
H-1A), 4.95 (br s, 1H, H-1B), 6.24 (dd, 1H0, JZ3.2, 0.5 Hz,
H-30), 6.35 (dd, 1H, JZ3.2, 1.8 Hz, H-4 ), 6.61 (m, 2H,
H-Ph), 7.03 (m, 2H, H-Ph), 7.41 (dd, 1H, JZ1.8, 0.5 Hz,
H-50). Anal. Calcd for C16H19NO: C, 79.67; H, 7.88; N,
5.81. Found: C, 79.69; H, 7.85; N, 5.83.

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F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
3.1.4. 2-Methyl-4-N-(200-ethylphenyl)amino-4-(20-furyl)-
butene-1 (11d). Yield 65.03 g (85%); bp 141–143 8C/
(dd, 1H, JZ13.8, 8.7 Hz, H-3A), 2.67 (dd, 1H, JZ13.8,
5.3 Hz, H-3B), 3.78 (br s, 1H, NH), 4.54 (dd, 1H, JZ8.7,
5.3 Hz, H-4), 4.84 (br s, 1H0, H-1A), 4.88 (br s, 1H, H-1B),
6.15 (d, 1H, JZ3.1 Hz, H-3 ), 6.26 (dd, 1H, JZ3.1, 1.8 Hz,
H-40), 6.43 0(0 d, 1H, JZ7.9 Hz, H-600), 6.83 (br d, 1H, JZ
7.9 Hz, H-5 ), 6.86 (br s, 1H, H-300), 7.33 (d, 1H, JZ1.8 Hz,
H-50). Anal. Calcd for C17H21NO: C, 80.00; H, 8.23; N,
5.49. Found: C, 80.20; H, 8.27; N, 5.52.
4 mmHg; n2D2 1.5502; IR3417 (NH), and 1651 (C]C) cmK1
;
1H NMR (CDCl3, 400 MHz) d 1.36 (t, 3H, JZ7.5 Hz,
CH2Me), 1.80 (br s, 3H, Me-2), 2.63 (q, 2H, JZ7.5 Hz,
CH2Me), 2.72 (dd, 1H, JZ13.9, 8.7 Hz, H-3A), 2.82 (dd,
1H, JZ13.9, 5.2 Hz, H-3B), 4.14 (br s, 1H, NH), 4.73 (dd,
1H, JZ8.7, 5.2 Hz, H-4), 4.98 (br s, 1H, H-1A), 5.01 (br s,
1H, H-1B), 6.26 (dd, 1H, JZ3.2, 0.8 Hz, H-30), 6.38 (dd,
1H, JZ3.2, 1.7 Hz, H-40), 6.66 (d, 1H, JZ7.8 Hz, H-Ph),
6.80 (t, 1H, JZ7.8 Hz, H-Ph), 7.15 (t, 1H, JZ7.8 Hz,
H-Ph), 7.170(d, 1H, JZ7.8 Hz, H-Ph), 7.44 (dd, 1H, JZ1.7,
0.8 Hz, H-5 ). Anal. Calcd for C17H21NO: C, 80.00; H, 8.23;
N, 5.49. Found: C, 80.21; H, 8.25; N, 5.39.
3.1.9. 2-Methyl-4-N-(400-isopropylphenyl)amino-4-(20-
furyl)butene-1 (11i). Yield 45.99 g (57%); bp 150–
151 8C/1 mmHg; n2D2 1.5435; IR 3390 (NH), and 1635
1
(C]C) cmK1; H NMR (CDCl3, 400 MHz) d 1.23 (d, 6H,
JZ7.0 Hz, CHMe2), 1.73 (br s, 3H Hz, Me-2), 2.58 (dd, 1H,
JZ14.1, 8.7 Hz, H-3A), 2.68 (dd, 1H, JZ14.1, 5.7 Hz,
H-3B), 2.82 (sept, 1H, JZ7.0 Hz, CHMe2), 2.92 (br s, 1H,
NH), 4.58 (dd, 1H, JZ8.7, 5.7 Hz, H-4), 4.85 (br d, 1H, JZ
0.7 Hz, H-1A), 4.90 (br d0, 1H, JZ0.7 Hz, H-1B), 6.22 (dd,
1H, 0 JZ3.0, 0.70Hz, H-3 ), 6.32 (dd, 1H, JZ3.0, 1.7 Hz,
H-4 ), 6.59 (BB , 2H, H-Ph), 7.04 (AA0, 2H, H-Ph), 7.37
(dd, 1H, JZ1.7, 0.7 Hz, H-50). Anal. Calcd for C18H23NO:
C, 80.30; H, 8.55; N, 5.20. Found: C, 80.32; H, 8.66; N,
5.42.
3.1.5. 2-Methyl-4-N-(200-methoxyphenyl)amino-4-(20-
furyl)butene-1 (11e). Yield 35.47 g (46%); bp 153–
154 8C/3 mmHg; n2D2 1.5578; IR 3411 (NH), and 1640
1
(C]C) cmK1; H NMR (CDCl3, 400 MHz) d 1.75 (br s,
3H, Me-2), 2.66 (dd, 1H, JZ14.0, 8.0 Hz, H-3A), 2.73 (dd,
1H, JZ14.0, 5.9 Hz, H-3B), 3.88 (s, 3H, OMe), 4.63 (dd,
1H, JZ8.0, 5.9 Hz, H-4), 4.68 (br s, 1H, NH), 4.87 (br s, 1H,
H-1A), 4.91 (br s, 1H, H-1B), 6.22 (d, 1H, JZ3.1 Hz, H-30),
6.32 (dd, 1H, JZ3.1, 1.7 Hz, H-40), 6.61 (dd, 1H, JZ7.8,
1.4 Hz, H-Ph), 6.71 (dt, 1H, JZ7.8, 1.4 Hz, H-Ph), 6.81 (dd,
1H, JZ7.8, 1.4 Hz, H-Ph), 6.84 (dt, 1H, JZ7.8, 1.4 Hz,
H-Ph), 7.38 (d, 1H, JZ1.7 Hz, H-50). Anal. Calcd for
C16H19NO2: C, 74.71; H, 7.39; N, 5.45. Found: C, 74.75; H,
7.36; N, 5.42.
3.1.10. 4-N-Phenylamino-4-(20-furyl)butene-1 (12a).
Yield 48.56 g (76%); bp 155–156 8C/7 mmHg; n2D0 1.5640;
1
IR 3398 (NH), and 1630 (C]C) cmK1; H NMR (CDCl3,
200 MHz) d 2.75 (t, 2H, JZ6.4 Hz, H-3), 4.04 (br s, 1H,
NH), 4.65 (t, 1H, JZ6.4 Hz, H-4), 5.24 (dd, 1H, JZ17.4,
1.2 Hz, H-1trans), 5.26 (dd, 1H, JZ10.0, 1.2 Hz, H-1cis),
5.85 (ddt, 1H, JZ17.4, 10.0, 6.4 Hz, H-2), 6.24 (dd, 1H, JZ
3.1, 0.8 Hz, H-30), 6.35 (dd, 1H, JZ3.1, 1.8 Hz, H-40), 6.69
(d, 2H, JZ7.5 Hz, H-Ph), 6.78 (t, 1H, JZ7.5 Hz, H-Ph),
7.23 (t, 2H, JZ7.5 Hz, H-Ph), 7.41 (dd, 1H, JZ1.8, 0.8 Hz,
H-50). Anal. Calcd for C14H15NO: C, 78.87; H, 7.04; N,
6.57. Found: C, 78.89; H, 7.06; N, 6.57.
3.1.6. 2-Methyl-4-N-(400-methoxyphenyl)amino-4-(20-
furyl)butene-1 (11f). Yield 57.83 g (75%); bp 156–
158 8C/2 mmHg; n2D3 1.5566; IR 3374 (NH), and 1640
1
(C]C) cmK1; H NMR (CDCl3, 200 MHz) d 1.71 (br s,
3H, Me-2), 2.56 (dd, 1H, JZ13.8, 8.1 Hz, H-3A), 2.66 (dd,
1H, JZ13.8, 6.0 Hz, H-3B), 3.74 (s, 3H, OMe), 4.51 (dd,
1H, JZ8.1, 6.0 Hz, H-4), 4.83 (br s, 1H, H-1A), 4.89 (br s,
1H, H-1B), 6.180(d, 1H, JZ3.2 Hz, H-30), 6.30 (dd, 1H, JZ
3.2, 1.8 Hz, H-4 ), 6.59 (m, 2H, H-Ph), 6.76 (m, 2H, H-Ph),
7.36 (d, 1H, JZ1.8 Hz, H-50). Anal. Calcd for C16H19NO2:
C, 74.71; H, 7.39; N, 5.45. Found: C, 74.73; H, 7.39; N,
5.46.
3.1.11. 4-N-(200-Methylphenyl)amino-4-(20-furyl)butene-
1 (12b). Yield 53.12 g (78%); bp 140–142 8C/4 mmHg; nD20
1
1.5576; IR 3419 (NH), and 1628 (C]C) cmK1; H NMR
(CDCl3, 400 MHz) d 2.21 (s, 3H, Me-200), 2.71 (dd, 2H, JZ
7.1, 6.1 Hz, H-3), 3.95 (br s, 1H, NH), 4.62 (t, 1H, JZ
6.1 Hz, H-4), 5.20 (dd, 1H, JZ10.4, 1.8 Hz, H-1cis), 5.24
(dd, 1H, JZ17.1, 1.8 Hz, H-1trans), 5.82 (ddt, 10H, JZ17.1,
10.4, 7.1 Hz, H-2), 6.19 (d, 1H, JZ3.1 Hz, H-3 ), 6.33 (dd,
1H, JZ3.1, 1.8 Hz, H-40), 6.60 (d, 1H, JZ8.4 Hz, H-Ph),
6.70 (t, 1H, JZ8.4 Hz, H-Ph), 7.09 (d, 1H, JZ8.4 Hz,
H-Ph), 7.10 (t, 1H, JZ8.4 Hz, H-Ph), 7.39 (d, 1H, JZ
1.8 Hz, H-50). Anal. Calcd for C15H17NO: C, 79.30; H, 7.49;
N, 6.17. Found: C, 79.30; H, 7.51; N, 6.19.
3.1.7. 2-Methyl-4-N-(200-benzylphenyl)amino-4-(20-
furyl)butene-1 (11g). Yield 75.13 g (79%); bp 185–
195 8C/2.5 mmHg; n2D0 1.5833; IR 3398 (NH), and 1650
1
(C]C) cmK1; H NMR (CDCl3, 400 MHz) d 1.64 (br s,
3H, Me-2), 2.50 (dd, 1H, JZ13.9, 8.4 Hz, H-3A), 2.64 (dd,
1H, JZ13.9, 5.4 Hz, H-3B), 4.01 (br s, 2H, CH2Ph), 4.66
(dd, 1H, JZ8.4, 5.4 Hz, H-4), 4.72 (br s, 1H, H-1A), 4.75
(m, 1H, H-1B), 5.99 (d, 1H, JZ3.2 Hz, H-30), 6.30 (dd, 1H,
JZ3.2, 1.8 Hz, H-40), 6.66 (dd, 1H, JZ7.5, 1.2 Hz, H-Ph),
6.81 (dt, 1H, JZ7.5, 1.2 Hz, H-Ph), 7.15 (dd, 1H, JZ7.5,
1.2 Hz, H-Ph), 7.19 (dt,01H, JZ7.5, 1.2 Hz, H-Ph), 7.37 (d,
1H, JZ1.8 Hz Hz, H-5 ), 7.25–7.39 (m, 5H, H-Ph). Anal.
Calcd for C22H23NO: C, 83.28; H, 7.26; N, 4.42. Found: C,
83.29; H, 7.30; N, 4.45.
3.1.12. 4-N-(200-Methoxyphenyl)amino-4-(20-furyl)-
butene-1 (12c). Yield 45.93 g (63%); bp 156–158 8C/
2 mmHg; n2D3 1.5636; IR 3407 (NH), and 1640
1
(C]C) cmK1; H NMR (CDCl3, 400 MHz) d 2.72 (t, 2H,
JZ7.0 Hz, H-3), 3.88 (s, 3H, OMe), 4.58 (t, 1H, JZ7.0 Hz,
H-4), 4.66 (br s, 1H, NH), 5.15 (dd, 1H, JZ10.1, 1.3 Hz,
H-1cis), 5.20 (dd, 1H, JZ17.1, 1.3 Hz, H-1trans), 5.81 (ddt,
1H, 0JZ17.1, 10.1, 7.0 Hz, H-2), 6.20 (br d, 1H, JZ3.0 Hz,
H-3 ), 6.31 (dd, 1H, JZ3.0, 1.7 Hz, H-40), 6.60 (dd, 1H, JZ
7.7, 1.5 Hz, H-Ph), 6.70 (dt, 1H, JZ7.7, 1.5 Hz, H-Ph), 6.80
(dd, 1H, JZ7.7, 1.5 Hz, H-Ph), 6.84 (dt, 1H, JZ7.7, 1.5 Hz,
H-Ph), 7.37 (dd, 1H, JZ1.7, 0.7 Hz, H-50). Anal. Calcd for
3.1.8. 2-Methyl-4-N-(20,40-dimethylphenyl)amino-4-(20-
furyl)butene-1 (11h). Yield 38.25 g (50%); bp 142–
145 8C/3 mmHg; n2D1 1.5500; IR 3417 (NH), and 1620
1
(C]C) cmK1; H NMR (CDCl3, 400 MHz) d 1.67 (br s,
3H, Me-2), 2.12 (s, 3H, Me-Ar), 2.19 (s, 3H, Me-Ar), 2.58

F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
4105
C15H17NO2: C, 74.07; H, 6.99; N, 5.76. Found: C, 74.09; H,
7.00; N, 5.76.
(11), 228 (39), 186 (100), 135 (24), 117 (12), 107 (14), 91
(21), 79 (7), 65 (6), 55 (6), 43 (9), 39 (5); 1H NMR (CDCl3,
200 MHz) d 1.77 (s, 3H, Ac), 2.42–2.58 (m, 2H, H-3), 3.79
(s, 3H, OMe); 5.10 (dq, 1H, JZ10.3, 1.5 Hz, H-1cis), 5.14
(dq, 1H, JZ17.3, 1.7 Hz, H-1trans), 5.83 (dddd, 1H, JZ
17.3, 10.3, 7.1, 5.9 Hz, H-2), 6.02 (dd, 1H, JZ3.1, 0.8 Hz,
H-30), 6.20 (t, 1H, JZ7.9 Hz, H-4); 6.24 (dd, 1H, JZ3.1,
1.8 Hz, H-400), 6.79 (br s, 4H, H-Ph), 7.33 (dd, 1H, JZ1.8,
0.8 Hz, H-5 ). Anal. Calcd for C16H17NO2: C, 75.29; H,
6.67; N, 5.49. Found: C, 75.31; H, 6.69; N, 5.52.
3.1.13. 4-N-(400-Methoxyphenyl)amino-4-(20-furyl)-
butene-1 (12d). Yield 48.11 g (66%); bp 158–160 8C/
4 mmHg; n2D3 1.6210; IR 3391 (NH), and 1619 (C]C) cmK1
;
1H NMR (CDCl3, 200 MHz) d 2.62 (t, 2H, JZ6.7 Hz, H-3),
3.68 (s, 3H, OMe), 3.71 (br s, 1H, NH), 4.45 (t, 1H, JZ
6.7 Hz, H-4), 5.10 (dd, 1H, JZ17.1, 1.9 Hz, H-1trans), 5.13
(dd, 1H, JZ10.1, 1.9 Hz, H-1cis), 5.74 (ddt, 1H, JZ17.1,
10.1, 6.7 Hz, H-2), 6.12 0(dd, JZ3.4, 0.9 Hz, H-30), 6.25 (dd,
1H, JZ3.4, 1.8 Hz, H-4 ), 6.55 (m, 2H, H-Ph), 6.72 (m, 2H,
H-Ph), 7.31 (dd, 1H, JZ1.8, 0.9 Hz, H-50). Anal. Calcd for
C15H17NO2: C, 74.07; H, 6.99; N, 5.76. Found: C, 74.11; H,
6.97; N, 5.75.
3.3. N-p-Tolylacetamide (6) and N-acetyl-2-methyl-4-N-
(400-methylphenyl)amino-4-(20-furyl)butanol-2 (7)
A mixture of 3.30 g (11.66 mmol) of N-acetyl derivative 4
and 15 mL of 85% H3PO4 was stirred at 30 8C for 1 h. Then
it was diluted with water (200 mL) and basified with 25%
aqueous ammonia to pH 9–10. The mixture was extracted
with ethyl acetate (3!50 mL) and the extract was dried
over Na2SO4. The crude crystalline product obtained after
evaporation of the solvent was chromatographed on Al2O3
(1.5!10 cm, hexane–ether–ethyl acetate) to give com-
pounds 6 and 7 as white crystals.
3.1.14. 4-N-(200,300-Dimethylphenyl)amino-4-(20-furyl)-
butene-1 (12e). Yield 54.95 g (76%); bp 168–171 8C/
4 mmHg; n2D3 1.5571; IR 3421 (NH), and 1629
1
(C]C) cmK1; H NMR (CDCl3, 200 MHz) d 2.17 (s, 3H,
Me-Ar), 2.37 (s, 3H, Me-Ar), 2.79 (t, 2H, JZ6.3 Hz, H-3),
4.66 (t, 1H, JZ6.3 Hz, H-4), 5.23 (dd, 1H, JZ10.0, 2.0 Hz,
H-1cis), 5.29 (dd, 1H, JZ17.1, 2.0 Hz, H-1trans), 5.88 (ddt,
1H, 0 JZ17.1, 10.0, 6.2 Hz, H-2), 6.23 (d, 1H, JZ3.2 Hz,
H-3 ), 6.36 (dd, 1H, JZ3.2, 1.8 Hz, H-40), 6.55 (d, 1H, JZ
8.1 Hz, H-Ph), 6.67 (d, 1H, JZ7.5 Hz, H-Ph), 7.04 (dd, 1H,
JZ8.1, 7.5 Hz, H-Ph), 7.43 (d, 1H, JZ1.8 Hz, H-50). Anal.
Calcd for C16H19NO: C, 79.67; N, 7.88; H, 5.81. Found: C,
79.69; N, 7.90; H, 5.80.
3.3.1. Compound 6. Yield 37%; mp 149 8C.
3.3.2. Compound 7. White crystals; yield 0.60 g (17%); Rf
(20% ethyl acetate–hexane) 0.42; IR 3320 (OH), and 1700
1
(N–C]O) cmK1; H NMR (CDCl3, 200 MHz) d 1.49 (s,
3H, Me), 1.51 (s, 3H, Me), 1.90 (s, 3H, Me), 2.20 (s, 3H,
Me-400), 2.28 (dd, 1H, JZ14.8, 7.5 Hz, H-3A), 2.34 (dd, 1H,
JZ14.8, 5.5 Hz, H-3B), 4.00 (br s, 1H, OH), 4.61 (dd, 1H,
JZ7.5, 5.5 Hz, H-4), 6.13 (d, 1H, JZ3.2 Hz, H-30), 6.25
(dd, 1H, JZ3.2, 1.8 Hz, H-40), 6.50 (m, 2H, H-Ph), 6.94 (m,
2H, H-Ph), 7.31 (d, 1H, JZ1.8 Hz, H-50). Anal. Calcd for
C18H23NO3: C, 71.76; H, 7.64; N, 4.65. Found: C, 71.78; H,
7.69; N, 4.65.
3.2. N-Acetyl-4-N-arylamino-4-(20-furyl)butene-1 (4, 18).
Typical procedure
Homoallylamine 11c or 12d (0.10 mol) was refluxed in
10-fold molar excess of acetic anhydride (w100 mL) for
1 h. An excess of the anhydride was removed in vacuo. The
residue was diluted with water (200 mL), and the solution
was basified with sodium carbonate to pH 9–10. The
mixture was extracted with ether (3!70 mL), and dried
over MgSO4. After solvent distillation, the residue was
purified on Al2O3 (3!10 cm, ethyl acetate–hexane) in case
of 4 or by recrystallization in case of 18.
3.4. 4-Oxo-3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-ene-6-
carboxylic acids 13a–i and 14a–e. Typical procedure
Corresponding amine 11, 12 (0.10 mol) was dissolved in
250 mL of benzene. Then an equimolar amount of maleic
anhydride (0.10 mol, 9.80 g) was added in one portion to the
solution. The reaction mixture was stirred for 1–7 days at
room temperature. Then the crystalline product was filtered
off, washed with benzene (2!100 mL) and ether (2!
80 mL) and dried at 100 8C to give desired products 13, 14
as white solids.
3.2.1. N-Acetyl-2-methyl-4-N-(400-methylphenyl)amino-
4-(20-furyl)butene-1 (4). Colorless oil; yield 25.19 g
(89%); Rf (20% ethyl acetate–hexane) 0.58; n2D4 1.5400;
IR 1656 (N–C]O, and C]C) cmK1; EI-MS (70 eV) m/z
(rel intensity): MC 323 (100), 306 (26), 279 (85), 249 (23),
234 (19), 220 (14), 204 (13), 191 (9), 165 (5), 153 (6), 132
1
(5), 103 (5), 77 (9), 36 (6), 28 (10); H NMR (CDCl3,
200 MHz) d 1.77 (s, 3H, Me), 1.78 (s, 3H, Me), 2.34 (s, 3H,
Me-400), 2.40 (dd, 1H, JZ15.0, 7.7 Hz, H-3A), 2.51 (dd, 1H,
JZ15.0, 7.7 Hz, H-3B), 4.81 (br s, 1H, H-1A), 4.86 (br s,
1H, H-1B), 6.07 (d, 1H, JZ3.2 Hz, H-30), 6.25 (dd, 1H, JZ
3.2, 1.9 Hz, H-40), 6.36 (t, 1H, JZ7.7 Hz, H-4), 6.67 (m,
2H, 0 H-Ph), 7.08 (m, 2H, H-Ph), 7.33 (d, 1H, JZ1.9 Hz,
H-5 ). Anal. Calcd for C18H21NO2: C, 76.32; H, 7.42; N,
4.95. Found: C, 76.30; H, 7.42; N, 4.98.
3.4.1. 4-Oxo-3-phenyl-2-methallyl-3-aza-10-oxatri-
cyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (13a). Ratio
of isomers A/Bw1/1; yield 31.20 g (96%); mp 185.5 8C; IR
1738 (COOH), and 1672 (N–C]O) cmK1; EI-MS (70 eV)
m/z (rel intensity): MC 325 (4), 270 (18), 240 (3), 226 (11),
172 (100), 170 (12), 135 (10), 117 (9), 99 (9), 91 (10), 77
1
(17), 44 (6); H NMR (DMSO-d6, 200 MHz) isomer A d
1.71 (br s, 3H), 2.18–2.23 (m, 2H), 2.56 (d, 1H, JZ9.2 Hz),
2.94 (d, 1H, JZ9.2 Hz), 4.78 (br s, 1H), 4.85 (br s, 1H), 5.01
(dd, 1H, JZ8.4, 6.0 Hz), 5.08 (d, 1H, JZ1.5 Hz), 6.37 (dd,
1H, JZ5.8, 1.5 Hz), 6.59 (d, JZ5.8 Hz), 7.05–7.60 (m,
5H), 11.50 (br s, 1H); isomer B d 1.70 (br s, 3H), 2.18–2.23
(m, 2H), 2.57 (d, 1H, JZ9.2 Hz), 3.20 (d, 1H, JZ9.2 Hz),
3.2.2. N-Acetyl-4-N-(400-methoxyphenyl)amino-4-(20-
furyl)butene-1 (18). Colorless needle like crystals; yield
22.19 g (87%); mp 40.5–41.5 8C; IR 1656 (N–C]O, and
C]C) cmK1; EI-MS (70 eV) m/z (rel intensity): MC 283

4106
F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
4.75 (br d, 1H, JZ4.4 Hz), 4.78 (br s, 1H), 4.85 (br s, 1H),
5.01 (d, 1H, JZ1.5 Hz), 6.48 (dd, 1H, JZ5.8, 1.5 Hz), 6.54
(d, JZ5.8 Hz), 7.05–7.60 (m, 5H), 11.50 (br s, 1H). Anal.
Calcd for C19H19NO4: C, 70.15; H, 5.85; N, 4.31. Found: C,
70.16; H, 5.83; N, 4.29.
1H, JZ9.5 Hz), 4.65 (br s, 1H), 4.70 (br s, 1H), 5.08 (dd,
1H, JZ6.0, 8.7 Hz), 5.10 (d, 1H, JZ1.8 Hz), 6.37 (dd, 1H,
JZ5.8, 1.8 Hz), 6.54 (d, 1H, JZ5.8 Hz), 7.15–7.35 (m,
4H). Anal. Calcd for C21H23NO4: C, 71.39; H, 6.51; N, 3.97.
Found: C, 71.37; H, 6.55; N, 3.95.
3.4.2. 4-Oxo-3-(200-methylphenyl)-2-methallyl-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (13b).
Ratio of isomers A/Bw1.7/1; yield 27.46 g (81%); mp
231–234 8C (decomp.); IR 1744 (COOH), and 1672
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
339 (2), 284 (24), 254 (2), 240 (7), 224 (4), 187 (14), 186
(100), 184 (8), 156 (98), 135 (8), 130 (12), 118 (14), 107 (6),
3.4.5. 4-Oxo-3-(200-methoxyphenyl)-2-methallyl-3-aza-
10-oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid
(13e). Ratio of isomers A/Bw1.6/1; yield 23.78
(67%); mp 172–174 8C; IR 1742 (COOH), and 1658
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
355 (7), 301 (5), 300 (27), 270 (2), 256 (8), 221 (5), 203
(14), 202 (100), 187 (4), 135 (13), 134 (11), 123 (6), 117 (9),
1
1
91 (19), 79 (5), 65 (7); H NMR (DMSO-d6, 400 MHz)
107 (5), 94 (6), 91 (12), 79 (7), 77 (9); H NMR (CDCl3,
isomer A d 1.64 (s, 3H); 1.88 (dd, 1H, JZ14.2, 3.6 Hz), 2.10
(s, 3H), 2.55 (d, 1H, JZ9.1 Hz), 2.69 (dd, 1H, JZ14.2,
10.2 Hz), 2.92 (d, 1H, JZ9.1 Hz), 4.66 (br s, 1H), 4.70 (br s,
1H), 4.95 (dd, 1H, JZ10.2, 3.6 Hz), 5.09 (d, 1H, JZ
0.9 Hz), 6.37 (dd, 1H, JZ5.7, 0.9 Hz), 6.54 (d, 1H, JZ
5.7 Hz), 7.16–7.31 (m, 4H), 12.18 (br s, 1H); isomer B d
1.57 (s, 3H), 2.16 (s, 3H), 2.24 (m, 1H), 2.41 (m, 1H), 2.53
(d, 1H, JZ8.7 Hz), 3.19 (br d, 1H, JZ8.7 Hz), 4.75 (t, 1H,
JZ5.5 Hz), 4.76 (br s, 1H), 4.77 (br s, 1H), 5.04 (d, 1H, JZ
1.0 Hz), 6.46 (dd, 1H, JZ5.7, 1.0 Hz), 6.57 (d, 1H, JZ
5.7 Hz), 7.16–7.31 (m, 4H) 12.18 (br s, 1H). Anal. Calcd for
C20H21NO4: C, 70.80; H, 6.19; N, 4.13. Found: C, 70.85; H,
6.17; N, 4.10.
400 MHz) isomer A d 1.69 (s, 3H), 2.03 (dd, 1H, JZ13.2,
3.8 Hz), 2.39 (dd, 1H, JZ13.2, 10.9 Hz), 2.84 (d, 1H, JZ
9.1 Hz), 3.07 (d, 1H, JZ9.1 Hz), 3.86 (s, 3H), 4.70 (br s,
1H), 4.76 (br s, 1H), 4.92 (dd, 1H, JZ10.9, 3.8 Hz), 5.25 (d,
1H, JZ1.6 Hz), 6.33 (dd, 1H, JZ5.7, 1.6 Hz), 6.47 (d, 1H,
JZ5.7 Hz), 6.90–7.00 (m, 2H), 7.20–7.35 (m, 2H); isomer
B d 1.64 (s, 3H), 2.44 (m, 2H, JZ9.2, 5.6 Hz), 2.84 (d, 1H,
JZ9.1 Hz), 3.17 (d, 1H, JZ9.1 Hz), 3.81 (s, 3H), 4.64 (dd,
1H, JZ9.2, 5.6 Hz), 4.76 (br s, 1H), 4.81 (br s, 1H), 5.27 (d,
1H, JZ1.7 Hz), 6.40 (dd, 1H, JZ5.7, 1.7 Hz), 6.57 (d, 1H,
JZ5.7 Hz), 6.90–7.00 (m, 2H), 7.20–7.35 (m, 2H). Anal.
Calcd for C20H21NO5: C, 67.60; H, 5.92; N, 3.94. Found: C,
67.60; H, 5.95; N, 3.93.
3.4.3. 4-Oxo-3-(400-methylphenyl)-2-methallyl-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (13c).
Ratio of isomers A/Bw1/2; yield 32.21 g (95%); mp 191.5–
3.4.6. 4-Oxo-3-(400-methoxyphenyl)-2-methallyl-3-aza-
10-oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid
(13f). Ratio of isomers A/Bw1.3/1; yield 29.11 g
(82%); mp 187–188.5 8C; IR 1745 (COOH), and 1672
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
355 (12), 337 (5), 311 (2), 300 (26), 256 (11), 221 (39), 202
(100), 186 (21), 161 (9), 149 (5), 135 (37), 117 (19), 107
192.5 8C; IR 1747 (COOH), and 1680 (N–C]O) cmK1
;
EI-MS (70 eV) m/z (rel intensity): MC 339 (6), 323 (5), 282
(12), 254 (2), 240 (6), 186 (100), 160 (3), 145 (5), 135 (8),
118 (15), 99 (13), 91 (37), 77 (16), 71 (5), 65 (9), 55 (9); 1H
NMR (DMSO-d6, 200 MHz) isomer B d 1.72 (br s, 3H),
2.15–2.24 (m, 2H), 2.31 (s, 3H), 2.56 (d, 1H, JZ9.2 Hz),
2.92 (d, 1H, JZ9.2 Hz), 4.76 (br s, 1H), 4.85 (br s, 1H), 4.97
(dd, 1H, JZ8.1, 5.8 Hz), 5.07 (d, 1H, JZ1.5 Hz), 6.36 (dd,
1H, JZ5.8, 1.5 Hz), 6.53 (d, 1H, JZ5.8 Hz), 7.14 (BB0,
2H), 7.23 (AA0, 2H), 11.50 (br s, 1H); isomer A d 1.70 (br s,
3H), 2.15–2.24 (m, 2H), 2.29 (s, 3H) 2.55 (d, 1H, JZ
9.2 Hz), 3.17 (d, 1H, JZ9.2 Hz), 4.69 (dd, 1H, JZ9.5,
3.9 Hz), 4.76 (br s, 2H), 5.00 (d, 1H, JZ1.5 Hz), 6.47 (dd,
1H, JZ5.8, 1.5 Hz), 6.58 (d, 1H, JZ5.8 Hz), 7.19 (BB0,
2H), 7.40 (AA0, 2H), 11.50 (br s, 1H). Anal. Calcd for
C20H21NO4: C, 70.80; H, 6.19; N, 4.13. Found; C, 70.78; H,
6.16; N, 4.13.
1
(10), 91 (16), 77 (12), 55 (14), 44 (9); H NMR (CDCl3,
400 MHz) isomer A d 1.71 (br s, 3H), 2.25 (dd, 1H, JZ13.5,
3.7 Hz), 2.43 (dd, 1H, JZ13.5, 10.8 Hz), 2.85 (d, 1H, JZ
9.0 Hz), 3.02 (d, 1H, JZ9.0 Hz), 3.81 (s, 3H), 4.69 (dd, 1H,
JZ10.8, 3.7 Hz), 4.77 (br s, 1H), 4.82 (br s, 1H), 5.31 (d,
1H, JZ1.7 Hz), 5.35 (dd, 1H, JZ5.7, 1.7 Hz), 6.44 (d, 1H,
JZ5.7 Hz), 6.92 (BB0, 2H), 7.15 (AA0, 2H), 11.50 (br s,
1H); isomer B d 1.71 (br s, 3H), 2.37 (dd, 1H, JZ15.9,
10.4 Hz), 2.56 (dd, 1H, JZ15.9, 3.7 Hz), 2.85 (d, 1H, JZ
9.0 Hz), 3.15 (d, 1H, JZ9.0 Hz), 3.80 (s, 3H), 4.61 (dd, 1H,
JZ10.4, 3.7 Hz), 4.81 (br s, 1H), 4.90 (br s, 1H), 5.26 (d,
1H, JZ1.7 Hz), 6.42 (dd, 1H, JZ5.7, 1.7 Hz), 6.57 (d, 1H,
JZ5.7 Hz), 6.90 (BB0, 2H), 7.31 (AA0, 2H), 11.50 (br s,
1H). Anal. Calcd for C20H21NO5: C, 67.60; H, 5.92; N, 3.94.
Found: C, 67.60; H, 5.90; N, 3.98.
3.4.4. 4-Oxo-3-(200-ethylphenyl)-2-methallyl-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (13d).
Ratio of isomers A/Bw1.5/1; yield 22.59 (64%); mp
225 8C; IR 1737 (COOH, and N–C]O) cmK1; EI-MS
(70 eV) m/z (rel intensity): MC 353 (1), 218 (20), 182 (7),
172 (7), 144 (30), 132 (18), 120 (15), 105 (8), 99 (24), 91
(20), 77 (20), 65 (7); 1H NMR (DMSO-d6, 200 MHz)
isomer A d 1.11 (t, 3H, JZ7.6 Hz), 1.58 (s, 3H), 1.87 (dd,
1H, JZ12.5, 4.0 Hz), 2.28 (dd, 1H, JZ12.5, 10.4 Hz), 2.50
(d, 1H, JZ9.2 Hz), 2.54 (q, 2H, JZ7.6 Hz), 2.91 (d, 1H,
JZ9.2 Hz), 4.77 (br s, 2H), 4.91 (dd, 1H, JZ10.4, 4.0 Hz),
5.06 (d, 1H, JZ1.8 Hz), 6.46 (dd, 1H, JZ5.8, 1.8 Hz), 6.58
(d, 1H, JZ5.8 Hz), 7.15–7.35 (m, 4H); isomer B d 1.09 (t,
3H, JZ7.6 Hz), 1.63 (br s, 3H), 2.45–2.60 (m, 5H), 3.16 (d,
3.4.7. 4-Oxo-3-(200-benzylphenyl)-2-methallyl-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (13g).
Ratio of isomers A/Bw1/4; yield 34.44 g (83%); mp 202–
203 8C; IR 1738 (COOH), and 1675 (N–C]O) cmK1
;
EI-MS (70 eV) m/z (rel intensity): MC 415 (11), 360 (30),
316 (8), 280 (35), 262 (100), 206 (9), 194 (15), 184 (8), 180
(17), 165 (18), 135 (11), 117 (10), 105 (5), 99 (11), 91 (29),
77 (6); 1H NMR (DMSO-d6, 400 MHz) isomer B d 1.58 (br
s, 3H), 1.75 (dd, 1H, JZ13.3, 3.3 Hz), 2.05 (dd, 1H, JZ
13.3, 10.8 Hz), 2.59 (d, 1H, JZ9.1 Hz), 2.94 (d, 1H, JZ
9.1 Hz), 3.71 (d, 1H, JZ15.5 Hz), 3.92 (d, 1H, JZ15.5 Hz),
4.58 (br s, 1H), 4.67 (br s, 1H), 4.98 (dd, 1H, JZ10.8,

F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
4107
3.3 Hz), 5.11 (s, 1H), 6.36 (d, 1H, JZ5.7 Hz), 6.53 (d, 1H,
JZ5.7 Hz), 7.05 (d, 1H, JZ7.6 Hz), 7.13–7.34 (m, 8H),
12.26 (br s, 1H); isomer A d 1.46 (br s, 3H), 1.79 (dd, 1H,
JZ13.2, 4.0 Hz), 2.24 (dd, 1H, JZ13.2, 11.1 Hz), 2.51 (d,
1H, JZ9.1 Hz), 2.94 (d, 1H, JZ9.1 Hz), 3.90 (m, 2H), 4.16
(dd, 1H, JZ11.1, 4.0 Hz), 4.48 (br s, 1H), 4.63 (br s, 1H),
5.05 (br s, 1H), 6.32 (dd, 1H, JZ6.0, 1.6 Hz), 6.36 (d, 1H,
JZ6.0 Hz), 6.94 (d, 1H, JZ7.9 Hz), 7.13–7.34 (m, 8H),
12.26 (br s, 1H). Anal. Calcd for C26H25NO4: C, 75.18; H,
6.02; N, 3.37. Found: C, 75.20; H, 6.00; N, 3.38.
1H, JZ10.4, 1.3 Hz), 5.27 (d, 1H, JZ1.8 Hz), 5.71 (dd, 1H,
JZ18.5, 10.4 Hz), 6.39 (dd, 1H, JZ5.8, 1.8 Hz), 6.47 (d,
1H, JZ5.8 Hz), 7.20–7.45 (m, 5H), 10.06 (br s, 1H); isomer
B d 2.62 (m, 2H), 2.86 (d, 1H, JZ9.2 Hz), 3.10 (d, 1H, JZ
9.2 Hz), 4.63 (t, 1H, JZ4.8 Hz), 5.17 (dd, 1H, JZ18.0,
1.3 Hz), 5.19 (dd, 1H, JZ9.3, 1.3 Hz), 5.33 (d, 1H, JZ
1.8 Hz), 5.77 (dd, 1H, JZ18.0, 9.3 Hz), 6.49 (dd, 1H, JZ
5.8, 1.8 Hz), 6.62 (d, 1H, JZ5.8 Hz), 7.20–7.45 (m, 5H),
10.06 (br s, 1H). Anal. Calcd for C18H17NO4: C, 69.45; H,
5.47; N, 4.50. Found: C, 69.49; H, 5.46; N, 4.54.
3.4.8. 4-Oxo-3-(200,400-dimethylphenyl)-2-methallyl-3-
aza-10-oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic
acid (13h). Ratio of isomers A/Bw1/1; yield 25.42 g
(72%); mp 235–236 8C; IR 1720 (COOH), and 1674
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
353 (2), 335 (2), 321 (7), 298 (10), 254 (5), 238 (5), 200
(100), 170 (9), 144 (22), 132 (12), 117 (10), 99 (12), 91 (14),
77 (9); 1H NMR (DMSO-d6, 200 MHz) isomer A d 1.62 (br
s, 3H), 1.89 (dd, 1H, JZ12.8, 4.0 Hz), 2.05 (s, 3H), 2.27
(s, 3H), 2.45 (dd, 1H, JZ12.8, 10.7 Hz), 2.52 (d, 1H, JZ
9.2 Hz), 2.89 (d, 1H, JZ9.2 Hz), 4.70 (br s, 1H), 4.77 (br s,
1H), 4.87 (dd, 1H, JZ10.7, 4.0 Hz), 5.08 (d, 1H, JZ
1.5 Hz), 6.36 (dd, 1H, JZ5.8, 1.5 Hz), 6.53 (d, 1H, JZ
5.8 Hz), 7.02–7.15 (m, 3H); isomer B d 1.60 (br s, 3H),
2.12 (s, 3H), 2.27 (br s, 3H), 2.50 (m, 2H), 2.55 (d, 1H, JZ
9.2 Hz), 3.13 (d, 1H, JZ9.2 Hz), 4.24 (dd, 1H, JZ9.2,
4.3 Hz), 4.66 (br s, 1H), 4.77 (br s, 1H), 5.03 (d, 1H, JZ
1.5 Hz), 6.44 (dd, 1H, JZ5.8, 1.5 Hz), 6.57 (d, 1H, JZ
5.8 Hz), 7.02–7.15 (m, 3H). Anal. Calcd for C21H23NO4: C,
71.39; H, 6.51; N, 3.97. Found: C, 71.39; H, 6.52; N, 4.00.
3.4.11. 4-Oxo-3-(200-methylphenyl)-2-allyl-3-aza-10-oxa-
tricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (14b).
Ratio of isomers A/Bw2/1; yield 27.30 g (84%);
mp 211.5–212 8C; IR 1744 (COOH), and 1673
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
325 (2), 307 (2), 284 (7), 253 (3), 226 (6), 195 (7), 186
(100), 118 (24), 99 (13), 91 (47), 77 (24), 65 (32), 55 (22);
1H NMR (DMSO-d6, 400 MHz) isomer A d 1.99 (m, 1H),
2.14 (s, 3H), 2.55 (d, 1H, JZ9.1 Hz), 2.59 (m, 1H), 2.94 (d,
1H, JZ9.1 Hz), 4.75 (dd, 1H, JZ10.6, 4.4 Hz), 4.93 (dd,
1H, JZ10.1, 1.7 Hz), 4.96 (dd, 1H, JZ17.0, 1.7 Hz), 5.04
(d, 1H, JZ1.7 Hz), 5.63 (ddt, 1H, JZ17.0, 10.1, 7.1 Hz),
6.41 (dd, 1H, JZ5.7, 1.7 Hz), 6.56 (d, 1H, JZ5.7 Hz),
7.20–7.29 (m, 4H). Anal. Calcd for C19H19NO4: C, 70.14;
H, 5.89; N, 4.30. Found: C, 70.41; H, 5.96; N, 4.24.
3.4.12. 4-Oxo-3-(200-methoxyphenyl)-2-allyl-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (14c).
Ratio of isomers A/Bw1.5/1; yield 19.10 g (56%); mp 152–
153 8C; IR 1755 (COOH), 1684 (N–C]O) cmK1; EI-MS
(70 eV) m/z (rel intensity): MC 341 (12), 300 (16), 282 (4),
256 (5), 242 (7), 202 (100), 186 (8), 134 (9), 121 (16), 99
3.4.9. 4-Oxo-3-(400-isopropylphenyl)-2-methallyl-3-aza-
10-oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid
(13i). Ratio of isomers A/Bw1/2.5; yield 30.09 g
(82%); mp 174–174.5 8C; IR 1725 (COOH), and 1675
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
367 (22), 312 (21), 268 (8), 214 (100), 198 (11), 172 (11),
146 (12), 135 (29), 117 (21), 99 (18), 91 (22), 77 (15), 65
(9), 55 (22), 19 (41); 1H NMR (DMSO-d6, 200 MHz)
isomer B d 1.19 (d, 6H, JZ6.7 Hz), 1.70 (s, 3H), 2.17 (d,
2H, JZ7.9 Hz), 2.55 (d, 1H, JZ9.2 Hz), 2.88 (sept, 1H, JZ
6.7 Hz), 2.93 (d, 1H, JZ9.2 Hz), 4.67 (m, 1H), 4.74 (m,
2H), 4.99 (m, 1H), 5.05 (d, 1H, JZ1.6 Hz), 6.35 (dd, 1H,
JZ5.6, 10.6 Hz), 6.51 (d, 1H, JZ5.6 Hz), 7.16 (BB0, 2H),
7.28 (AA , 2H); isomer A d 1.18 (d, 6H, JZ6.6 Hz), 1.70 (s,
3H), 2.37 (m, 1H), 2.51 (m, 1H), 2.53 (d, 1H, JZ9.2 Hz),
2.88 (sept, 1H, JZ6.6 Hz), 3.20 (d, 1H, JZ9.2 Hz), 4.85
(m, 1H), 4.99 (m, 2H), 4.99 (d, 1H, JZ1.6 Hz), 6.45 (dd,
1H, JZ5.8, 1.6 Hz), 6.55 (d, 1H, JZ5.8 Hz), 7.24 (BB0,
2H), 7. 43 (AA0, 2H). Anal. Calcd for C22H25NO4: C, 71.94;
H, 6.81; N, 3.82. Found: C, 71.96; H, 6.80; N, 3.84.
1
(12), 91 (21), 81 (12), 77 (30), 65 (15); H NMR (CDCl3,
200 MHz) isomer A d 2.18 (m, 1H), 2.57 (m, 1H), 2.91 (d,
1H, JZ9.2 Hz), 3.03 (d, 1H, JZ9.2 Hz), 3.84 (s, 3H), 4.70
(dd, 1H, JZ10.4, 4.6 Hz), 5.00 (br d, 1H, JZ10.4 Hz), 5.02
(br d, 1H, JZ17.1 Hz), 5.41 (d, 1H, JZ1.5 Hz), 5.68 (m,
1H), 6.45 (dd, 1H, JZ5.8, 1.5 Hz), 6.47 (d, 1H, JZ5.8 Hz),
6.95–7.05 (m, 2H), 7.20–7.40 (m, 2H); isomer B d 2.40 (m,
1H), 2.57 (m, 1H), 2.91 (d, 1H, JZ9.2 Hz), 3.02 (d, 1H, JZ
9.2 Hz), 3.87 (s, 3H), 4.53 (t, 1H, JZ5.2 Hz), 5.19 (br d, 1H,
JZ9.2 Hz), 5.21 (br d, 1H, JZ18.0 Hz), 5.41 (d, 1H, JZ
1.5 Hz), 5.89 (m, 1H), 6.52 (dd, 1H, JZ6.1, 1.5 Hz), 6.63
(d, 1H, JZ6.1 Hz), 6.95–7.05 (m, 2H), 7.20–7.40 (m, 2H).
Anal. Calcd for C19H19NO5: C, 66.86; H, 5.57; N, 4.10.
Found: C, 66.86; H, 5.56; N, 4.10.
3.4.13. 4-Oxo-3-(400-methoxyphenyl)-2-allyl-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (14d).
Ratio of isomers A/Bw1/1; yield 32.05 g (94%).
Isomer A mp 67.5–69.5 8C; IR 1720 (COOH), and 1685
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
341 (22), 300 (24), 256 (12), 242 (12), 221 (63), 202 (100),
186 (17), 161 (7), 134 (11), 123 (20), 121 (37), 103 (23); 93
3.4.10. 4-Oxo-3-phenyl-2-allyl-3-aza-10-oxatricyclo-
[5.2.1.01,5]dec-8-ene-6-carboxylic acid (14a). Ratio of
isomers A/Bw1/1; yield 27.06 g (87%); mp 180–182 8C;
IR 1749 (COOH), and 1670 (N–C]O) cmK1; EI-MS
(70 eV) m/z (rel intensity): MC 311 (8), 293 (5), 270 (20),
226 (12), 212 (23), 173 (15), 172 (100) 170 (16) 145 (6), 121
(13), 104 (13), 103 (16), 99 (12), 93 (13), 91 (21), 77 (36);
1H NMR (CDCl3, 400 MHz) isomer A d 2.41 (m, 2H), 2.84
(d, 1H, JZ9.2 Hz), 3.02 (d, 1H, JZ9.2 Hz), 4.59 (dd, 1H,
JZ9.8, 5.2 Hz), 5.07 (dd, 1H, JZ18.5, 1.3 Hz), 5.09 (dd,
1
(14), 77 (20), 55 (11). H NMR (DMSO-d6, 200 MHz) d
2.24 (ddd, 2H, JZ9.2, 6.8, 5.5 Hz), 2.57 (d, 1H, JZ9.2 Hz),
2.93 (d, 1H, JZ9.2 Hz), 3.77 (s, 3H), 4.73 (dd, 1H, JZ9.2,
5.5 Hz), 4.98 (dd, 1H, JZ10.1, 1.5 Hz), 5.03 (dd, 1H, JZ
18.0, 1.5 Hz), 5.08 (d, 1H, JZ1.5 Hz), 5.72 (ddt, 1H, JZ
18.0, 10.1, 6.8 Hz), 6.41 (dd, 1H, JZ5.8, 1.5 Hz), 6.55
(d, 1H, JZ5.8 Hz), 6.96 (BB0, 2H), 7.17 (AA0, 2H), 11.50

4108
F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
1
(br s, 1H); H NMR (CDCl3, 400 MHz) d 1.99 (m, 2H,
CH2-30), 2.79 (d, 1H, JZ9.2 Hz, H-6), 3.02 (d, 1H, JZ
9.2 Hz, H-5), 3.04 (s, 3H, MeO-400), 4.47 (t, 1H, JZ5.0 Hz,
H-2), 5.15 (m, 1H, H-10A), 5.17 (m, 1H, H-10B), 5.23 (d,
1H, 0JZ1.8 Hz, H-7), 5.74 (ddt, 1H, JZ16.8, 10.5, 7.0 Hz,
H-2 ), 6.45 (dd, 1H, JZ5.9, 1.8 0H0 z, H-8), 060 .57 (d, 1H, JZ
5.9 Hz, H-9), 6.88 (m, 2H, H-3 and H-5 ), 7.27 (m, 2H,
H-200 and H-600); 13C NMR (CDCl3, 100.6 MHz) d 33.6
1H); isomer B d 2.12 (s, 3H), 2.29 (s, 3H), 2.65 (m, 2H),
2.84 (d, 1H, JZ10.0 Hz), 2.98 (d, 1H, JZ10.0 Hz), 4.13
(dd, 1H, JZ5.8, 4.6 Hz), 5.01 (m, 1H, JZ10.7 Hz), 5.03 (m,
1H, JZ17.1 Hz), 5.38 (d, 1H, JZ1.5 Hz), 5.65 (m, 1H, JZ
16.8, 10.1 Hz), 6.39 (dd, 1H, JZ5.5, 1.5 Hz), 6.57 (br d, 1H,
JZ5.5 Hz), 6.95–7.00 (m, 1H), 7.05–7.25 (m, 2H), 12.00
(br s, 1H). Anal. Calcd for C20H21NO4: C, 70.80; H, 6.19; N,
4.13. Found: C, 70.83; H, 6.17; N, 4.13.
0
(t, JZ128.0 Hz, C3 ), 46.2 (d, JZ138.2 Hz, C6), 50.5 (d,
JZ139.3 Hz, C5), 55.3 (q, JZ144.2 Hz, MeO), 61.6 (d, JZ
146.3 Hz, C2), 81.5 (d, JZ169.0 Hz, C7), 91.3 (s, C1), 114.3
(d, JZ160.8 Hz, C3 and C5 ), 119.9 (dd, JZ154.0,
3.5. 6-Ethoxycarbonyl-4-oxo-3-aza-10-oxatricyclo-
[5.2.1.01,5]dec-8-enes (15a,b). Typical procedure
00
00
0
00
00
159.5 Hz, C1 ), 126.1 (d, JZ161.0 Hz, C2 and C6 ), 129.3
Adduct 14a,b (0.01 mol) was refluxed in ethanol (20 mL)
for 2 h in the presence of catalytic amounts of H2SO4
(concd). Then the reaction mixture was poured into 150 mL
of water and extracted with ethyl acetate (4!60 mL). The
extract was dried over MgSO4 and concentrated in vacuo.
The crude product was recrystallized from mixture of
hexane–ethyl acetate to give esters 15a,b as white solids.
00
0
(s, C1 ), 131.4 (d, JZ152.8 Hz, C2 ), 133.4 (d, JZ178.0 Hz,
00
C9), 137.2 (d, JZ177.5 Hz, C8), 158.0 (s, C4 ), 171.5 (s,
COOH), 173.5 (s, C4). Anal. Calcd for C19H19NO5: C,
66.86; H, 5.57; N, 4.10. Found: C, 66.88; H, 5.60; N, 4.10.
Isomer B mp 117.5–118 8C; IR 1740 (COOH), and 1675
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
341 (29), 300 (30), 256 (15), 242 (14), 221 (78), 202 (100),
186 (22), 161 (10), 134 (14), 123 (27), 121 (46), 108 (11),
3.5.1. 6-Ethoxycarbonyl-4-oxo-3-phenyl-2-allyl-3-aza-
10-oxatricyclo[5.2.1.01,5]dec-8-ene (15a). Ratio of isomers
A/Bw1.2/1; yield 2.37 g (70%); mp 74.5–76 8C; IR 1786
(COOEt), 1695 (N–C]O) cmK1; EI-MS (70 eV) m/z (rel
intensity): MC 339 (23), 298 (31), 270 (1), 212 (26), 200
(5), 172 (100), 127 (80), 121 (27), 104 (15), 99 (80), 91 (14),
77 (37), 65 (8); 1H NMR (DMSO-d6, 200 MHz) isomer A d
1.22 (t, 3H, JZ7.2 Hz), 2.25 (m, 2H), 2.68 (d, 1H, JZ
9.2 Hz), 3.02 (d, 1H, JZ9.2 Hz), 4.10 (d, 2H, JZ7.2 Hz),
4.85 (dd, 1H, JZ10.1, 4.6 Hz), 4.95–5.20 (m, 2H), 5.13 (d,
1H, JZ1.5 Hz), 5.78 (m, 1H), 6.42 (dd, 1H, JZ5.8, 1.5 Hz),
6.57 (d, 1H, JZ5.8 Hz), 7.10–7.60 (m, 5H); isomer B d 1.17
(t, 3H, JZ7.2 Hz), 2.59 (m, 2H), 2.68 (d, 1H, JZ9.2 Hz),
3.13 (d, 1H, JZ9.2 Hz), 4.02 (q, 2H, JZ7.2 Hz), 4.71 (dd,
1H, JZ5.5, 4.6 Hz), 4.95–5.20 (m, 2H), 5.05 (d, 1H, JZ
1.5 Hz), 5.78 (m, 1H), 6.52 (dd, 1H, JZ5.8, 1.5 Hz), 6.75
(d, 1H, JZ5.8 Hz), 7.10–7.60 (m, 5H). Anal. Calcd for
C20H21NO4: C, 70.80; H, 6.19; N, 4.13. Found: C, 70.83; H,
6.17; N, 4.12.
1
103 (29); 93 (18), 77 (26), 55 (14). H NMR (DMSO-d6,
200 MHz) d 2.48–2.59 (m, 2H), 2.55 (d, 1H, JZ9.2 Hz),
3.01 (d, 1H, JZ9.2 Hz), 3.76 (s, 3H), 4.57 (t, 1H, JZ
5.5 Hz), 5.01 (d, 1H, JZ1.5 Hz), 5.12 (br dd, 1H, JZ9.2,
1.5 Hz), 5.14 (dd, 1H, JZ18.3, 1.5 Hz), 5.82 (ddt, 1H, JZ
18.3, 9.2, 6.7 Hz), 6.52 (dd, 1H, JZ5.8, 1.5 Hz), 6.73
(d, 1H, JZ5.8 Hz), 6.95 (BB0, 2H), 7.41 (AA0, 2H), 11.57
1
(br s, 1H); H NMR (CDCl3, 400 MHz) d 2.30 (dddt, 1H,
JZ13.4, 7.7, 1.10 Hz, H-30A), 2.41 (dddt, 1H, JZ13.4, 10.8,
6.6, 1.1 Hz, H-3 B), 2.82 (d, 1H, JZ9.1 Hz, H-6), 3.00 (d,
1H, JZ9.1 Hz, H-5), 3.11 (s, 3H, MeO-400), 4.50 (dd, 1H,
JZ10.8, 4.5 Hz, H-2), 5.01 (m, 1H, H-10A), 5.04 (m, 1H,
H-10B), 5.27 (d, 1H, JZ1.8 Hz, H-7), 5.68 (dddd, 1H, JZ
17.0, 10.2, 7.7, 6.6 Hz, H-20), 6.38 (dd, 1H, JZ5.7, 1.8 Hz,
H-8), 6.46 (d, 1H, JZ5.7 Hz, H-9), 6.89 (m, 2H, H-300 and
H-500), 7.14 (m, 2H, H-200 and H-600); 13C NMR (CDCl3,
0
100.6 MHz) d 32.6 (t, JZ131.5 Hz, C3 ), 46.1 (d, JZ
140.0 Hz, C6), 50.6 (d, JZ140.0 Hz, C5), 55.3 (q, JZ
144.2 Hz, MeO), 60.1 (d, JZ141.7 Hz, C2), 81.6 (d, JZ
169.0 Hz, C7), 90.4 (s, C1), 114.2 (d, JZ160.0 Hz, C3 and
3.5.2. 6-Ethoxycarbonyl-4-oxo-3-(20-methylphenyl)-2-
allyl-3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-ene (15b).
Ratio of isomers A/Bw3/1; yield 3.07 g (87%); mp 115–
00
00
0
C5 ), 118.8 (dd, JZ154.5, 158.5 Hz, C1 ), 127.3 (d, JZ
116.5 8C; IR 1724 (COOEt), and 1697 (N–C]O) cmK1
;
00
00
00
160.5 Hz, C2 and C6 ), 128.6 (s, C1 ), 132.3 (d, JZ
154.8 Hz, C2 ), 135.6 (d, JZ177.8 Hz, C8), 135.8 (d, JZ
00
177.8 Hz, C9), 158.4 (s, C4 ), 172.2 (s, COOH), 173.4 (s,
EI-MS (70 eV) m/z (rel intensity): MC 353 (10), 312 (34),
307 (7), 232 (9), 226 (43), 210 (11), 186 (100), 156 (15), 144
(11), 127 (57), 121 (28), 99 (80), 91 (38), 65 (15), 39 (11);
1H NMR (CDCl3, 400 MHz) isomer A d 1.30 (t, 3H, JZ
7.1 Hz), 2.05–2.19 (m, 1H), 2.24 (s, 3H), 2.44–2.57 (m, 1H),
2.78 (d, 1H, JZ9.1 Hz), 2.93 (d, 1H, JZ9.1 Hz), 4.15–4.37
(m, 2H), 4.51 (dd, 1H, JZ10.8, 4.5 Hz), 5.01 (dd, 1H, JZ
10.0, 7.0 Hz), 5.04 (dd, 1H, JZ17.0, 7.0 Hz), 5.25 (d, 1H,
JZ1.6 Hz), 5.60–5.74 (m, 1H), 6.41 (dd, 1H, JZ5.7,
1.7 Hz), 6.52 (dd, 1H, JZ5.7, 1.3 Hz), 7.20–7.28 (m, 4H).
Anal. Calcd for C21H23NO4: C, 71.39; H, 6.51; N, 3.97.
Found: C, 71.42; H, 6.50; N, 3.40.
0
C4). Anal. Calcd for C19H19NO5: C, 66.86; H, 5.57; N, 4.10.
Found: C, 66.86; H, 5.58; N, 4.12.
3.4.14. 4-Oxo-3-(200,300-dimethylphenyl)-2-allyl-3-aza-10-
oxatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic acid (14e).
Ratio of isomers A/Bw2.5/1; yield 25.76 g (76%); mp
227 8C; IR 1747 (COOH), and 1672 (N–C]O) cmK1
;
EI-MS (70 eV) m/z (rel intensity): MC 339 (4), 321 (2), 299
(5), 298 (27), 254 (9), 240 (14), 201 (16), 200 (100), 198
(11), 170 (6), 159 (7), 132 (13), 130 (10), 121 (16), 120 (8),
105 (8), 103 (14), 99 (9), 91 (16), 77 (17); 1H NMR (DMSO-
d6, 200 MHz) isomer A d 2.12 (s, 3H), 2.29 (s, 3H), 2.65 (m,
2H), 2.85 (d, 1H, JZ10.0 Hz), 3.03 (d, 1H, JZ10.0 Hz),
4.49 (dd, 1H, JZ8.9, 5.0 Hz), 5.25 (dd, 2H, JZ16.8,
10.1 Hz), 5.33 (d, 1H, JZ1.5 Hz), 5.89 (dd, 1H, JZ16.8,
10.1 Hz), 6.50 (dd, 1H, JZ5.5, 1.5 Hz), 6.70 (br d, 1H, JZ
5.5 Hz), 6.95–7.00 (m, 1H), 7.05–7.25 (m, 2H), 12.00 (br s,
3.6. 11-Oxo-6,6a,9,10,10a,11-hexahydro-5H-6b,9-epoxy-
isoindolo[2,1-a]quinoline-10-carboxylic acids (20a,b).
Typical procedure
A mixture of the corresponding adduct 13c,d (0.01 mol) and
85% H3PO4 (30 mL) was stirred at 10–15 8C for 1.5 h

F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
4109
(monitoring by TLC). At the end of the reaction, the mixture
was diluted with water (150 mL). The obtained precipitate
was filtered off, washed with cold water (5!80 mL) and
dried in air. Then the crude product was recrystallized to
give the desired product 20 as colorless crystals.
C, 75.22; H, 6.27; N, 4.18. Found: C, 75.20; H, 6.29; N,
4.15.
3.7. 5,5-Dimethyl-10-carboxyisoindolo[2,1-a]quinoline-
11-ones (21a–i). Typical procedure
A mixture of corresponding adduct 13 (0.01 mol) and 85%
H3PO4 (40 mL) was stirred at 70–85 8C for 45 min
(monitoring by TLC). At the end of the reaction, the
mixture was diluted with water (200 mL). The obtained
precipitate was filtered off, washed with cold water (5!
80 mL) and dried in air. Then the crude product was
recrystallized to give desired isoindoloquinolines 21 as
colorless crystals.
3.6.1. 3,5,5-Trimethyl-11-oxo-6,6a,9,10,10a,11-hexa-
hydro-5H-6b,9-epoxyisoindolo[2,1-a]quinoline-10-carb-
oxylic acid (20a). Major isomer. Yield 1.25 g (37%); mp
215.5–217 8C decomp. (chloroform); IR 1746 (COOH), and
1672 (N–C]O, and C]C) cmK1; EI-MS (70 eV) m/z (rel
intensity): MC 339 (11), 321 (4), 294 (3), 240 (100), 224
(18), 196 (8), 181 (7), 158 (13), 144 (8), 115 (7), 91 (7), 81
1
(4); H NMR (DMSO-d6, 400 MHz) d 1.29 (s, 3H, Me-5),
1.35 (s, 3H, Me-5), 1.77 (dd, 1H, JZ13.5, 3.4 Hz, H-6A),
1.83 (dd, 1H, JZ13.5, 11.8 Hz, H-6B), 2.25 (s, 3H, Me-3),
2.56 (d, 1H, JZ9.1 Hz, H-10), 3.06 (d, 1H, JZ9.1 Hz,
H-10a), 4.62 (dd, 1H, JZ11.8, 3.4 Hz, H-6a), 5.02 (d, 1H,
JZ1.7 Hz, H-9), 6.49 (dd, 1H, JZ5.7, 1.7 Hz, H-8), 6.61 (d,
1H, JZ5.7 Hz, H-7), 6.95 (dd, 1H, JZ8.5, 2.0 Hz, H-2),
7.24 (d, 1H, JZ2.0 Hz, H-4), 8.47 (d, 1H, JZ8.5 Hz, H-1),
12.19 (br s, 1H, COOH); 13C NMR (DMSO-d6, 100.6 MHz)
d 173.2 (s), and 169.5 (s) (COOH, and C12), 137.6 (d, JZ
177.5 Hz, C8), 134.7 (d, JZ178.5 Hz, C7), 134.4, 133.1, and
132.1 (s, C4a, C3, C12a), 127.2 (d, JZ154.0 Hz, C4), 126.9
(d, JZ157.5 Hz, C2), 118.0 (d, JZ163.5 Hz, C1), 89.8 (s,
C6b), 81.0 (d, JZ168.5 Hz, C9), 52.5 (d, JZ142.5 Hz, C6a),
51.0 (d, JZ141.0 Hz, C10a), 45.1 (d, JZ138.5 Hz, C10),
37.1 (t, JZ131.5 Hz, C6), 32.6 (s, C5), 32.2 (q, JZ126.0 Hz,
Me-5), 30.5 (q, JZ126.0 Hz, Me-5), 20.7 (q, JZ126.5 Hz,
Me-3). Anal. Calcd for C20H21NO4: C, 70.80; H, 6.19; N,
4.13. Found: C, 70.82; H, 6.23; N, 4.17. Minor isomer (has
3.7.1. 5,5-Dimethyl-5,6,6a,11-tetrahydro-11-oxoiso-
indolo[2,1-a]quinoline-10-carboxylic acid (21a). Yield
2.09 g (68%); mp 237.5–240 8C (heptane–chloroform); IR
1727 (COOH), and 1617 (N–C]O) cmK1; EI-MS (70 eV)
m/z (rel intensity): MC 307 (92), 292 (65), 264 (21), 263
(100), 248 (18), 232 (11), 218 (15), 204 (12), 115 (9), 102
1
(7), 91 (6); H NMR (CDCl3, 400 MHz) d 1.47 (s, 3H,
Me-5), 1.54 (s, 3H, Me-5), 1.72 (t, 1H, JZ12.7 Hz, H-6ax),
2.41 (dd, 1H, JZ12.7, 2.6 Hz, H-6eq), 4.97 (dd, 1H, JZ
12.7, 2.6 Hz, H-6a), 7.23–7.39 (m, 2H, H-Ar), 7.48 (dd, 1H,
JZ7.3, 1.8 Hz, H-Ar), 7.76–7.86 (m, 2H, H-Ar), 8.38 (dd,
1H, JZ7.9, 1.5 Hz, H-1), 8.50 (dd, 1H, JZ7.9, 1.5 Hz,
H-9); 13C NMR (DMSO-d6, 100.6 MHz) d 166.2 (s), and
165.3 (s) (COOH, and N–C]O), 146.4 (s), 136.6 (s), 133.1
(s), 129.5 (s), 128.9 (s), 132.9 (d, C8), 131.7 (d, C9), 127.4
(d), 126.6 (d), 126.5 (d), 125.6 (d), 120.4 (d), 56.5 (d, C6a),
41.9 (t, C6), 33.6 (s, C5), 31.7 (q), and 30.6 (q) (Me-5). Anal.
Calcd for C19H17NO3: C, 74.27; H, 5.54; N, 4.56. Found: C,
74.22; H, 5.57; N, 4.59.
1
not been isolated). H NMR (DMSO-d6, 400 MHz) d 1.33
(s, 3H, Me-5), 1.37 (s, 3H, Me-5), 1.95 (t, 1H, JZ13.1 Hz,
H-6A), 2.12 (dd, 1H, JZ13.1, 2.1 Hz, H-6B), 2.25 (s, 3H,
Me-3), 2.57 (d, 1H, JZ9.1 Hz, H-10), 3.02 (d, 1H, JZ
9.1 Hz, H-10a), 4.05 (dd, 1H, JZ13.1, 2.1 Hz, H-6a), 5.08
(d, 1H, JZ1.7 Hz, H-9), 6.50 (dd, 1H, JZ5.7, 1.7 Hz, H-8),
6.71 (d, 1H, JZ5.7 Hz, H-7), 6.97 (dd, 1H, JZ8.2, 2.0 Hz,
H-2), 7.27 (d, 1H, JZ2.0 Hz, H-4), 7.61 (d, 1H, JZ8.2 Hz,
H-1), 12.19 (br s, 1H, COOH).
3.7.2. 1,5,5-Trimethyl-5,6,6a,11-tetrahydro-11-oxoiso-
indolo[2,1-a]quinoline-10-carboxylic acid (21b). Yield
1.00 g (31%); mp 209.5–210 8C (i-PrOH–DMF); IR 1728
(COOH), and 1619 (N–C]O) cmK1; EI-MS (70 eV) m/z
(rel intensity): MC 321 (79), 306 (12), 288 (13), 275 (100),
262 (12), 245 (4), 221 (12), 130 (14), 115 (25), 91 (15), 77
1
(18), 65 (12), 51 (13); H NMR (CDCl3, 400 MHz) d 1.30
(s, 3H, Me-5), 1.44 (s, 3H, Me-5), 1.72 (dd, 1H, JZ13.4,
10.3 Hz, H-6ax), 2.39 (s, 3H, Me-1), 2.42 (dd, 1H, JZ13.4,
4.7 Hz, H-6eq), 4.98 (dd, 1H, JZ10.3, 4.7 Hz, H-6a), 7.20–
7.30 (m, 3H, H-Ar), 7.77–7.79 (m, 2H, H-Ar), 8.45 (dd, 1H,
JZ5.8, 2.1, H-9); 13C NMR (DMSO-d6, 100.6 MHz) d
165.6 (s), and 165.4 (s) (COOH, and N–C]O), 148.7 (s),
139.5 (s), 132.7 (s), 131.7 (s), 129.8 (s), 128.5 (s), 133.0 (d,
C8), 131.4 (d, C9), 129.2 (d), 126.81 (d), 126.80 (d), 124.1
(d), 57.3 (d, C6a), 45.2 (t, C6), 33.2 (s, C5), 32.2 (q), and 30.2
(q) (Me-5), 20.0 (q, Me-1). Anal. Calcd for C20H19NO3: C,
74.77; N, 5.92; H, 4.36. Found: C, 74.80; N, 5.96; H, 4.32.
3.6.2. 1-Ethyl-5,5-dimethyl-11-oxo-6,6a,9,10,10a,11-
hexahydro-5H-6b,9-epoxyisoindolo[2,1-a]quinoline-10-
carboxylic acid (20b). Yield 2.22 g (63%); mp 150–151 8C
(heptane–chloroform); IR 1700 (COOH), and 1617
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
353 (4), 309 (2), 280 (4), 254 (100), 240 (16), 212 (12), 186
(13), 172 (13), 160 (16), 144 (12), 130 (10), 115 (11), 99
1
(20), 91 (7), 77 (4); H NMR (CDCl3, 400 MHz) d 1.17 (t,
3H, JZ7.7 Hz), 1.36 (s, 3H), 1.44 (s, 3H), 1.91 (t, 1H, JZ
12.8 Hz), 2.13 (dd, 1H, JZ12.9, 2.7 Hz), 2.75 (d, 2H, JZ
7.7 Hz), 2.83 (d, 1H, JZ8.8 Hz), 2.92 (d, 1H, JZ8.8 Hz),
4.23 (dd, 1H, JZ12.7, 2.7 Hz), 5.28 (d, 1H, JZ1.5 Hz),
6.49 (dd, 1H, JZ6.0, 1.5 Hz), 6.62 (d, 1H, JZ6.0 Hz), 7.12
(dd, 1H, JZ7.4, 2.4 Hz), 7.15 (t, 1H, JZ7.4 Hz), 7.19 (dd,
1H, JZ7.4, 2.4 Hz), 7.40 (br s, 1H); 13C NMR (DMSO-d6,
100.6 MHz) d 172.8 (s); 169.1 (s) (COOH and N–C]O);
139.0 (s); 138.8 (s); 132.4 (s); 136.8 (d) and 134.4 (d) (C7
and C8); 126.3 (d); 125.8 (d); 124.1 (d); 90.6 (s, C6b); 81.7
(d, C9); 55.2 (d, C6a); 49.4 (d, C10a); 45.1 (d, C10); 40.6 (t,
C6); 34.0 (s, C5); 33.2 (q) and 31.6 (q) (Me-5); 24.5 (t,
CH2CH3); 14.3 (q, CH2CH3). Anal. Calcd for C21H23NO4:
3.7.3. 3,5,5-Trimethyl-5,6,6a,11-tetrahydro-11-oxoiso-
indolo[2,1-a]quinoline-10-carboxylic acid (21c). Yield
1.61 g (50%); mp 222–230 8C decomposition (heptane–
chloroform); IR 1708 (COOH, and N–C]O) cmK1; EI-MS
(70 eV) m/z (rel intensity): MC 321 (1), 277 (66), 262 (100),
246 (14), 232 (17), 218 (3), 124 (6), 115 (9), 91 (4), 77 (7);
1H NMR (CDCl3, 400 MHz) d 1.45 (s, 3H, Me-5), 1.52 (s,
3H, Me-5), 1.69 (t, 1H, JZ13.0 Hz, H-6ax), 2.38 (s, 3H,
Me-3), 2.38 (dd, 1H, JZ13.0, 2.7 Hz, H-6eq), 4.92 (dd, 1H,

4110
F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
JZ13.0, 2.7 Hz, H-6a), 7.13 (dd, 1H, JZ8.5, 1.5 Hz, H-2),
7.25 (d, 1H, JZ1.5 Hz, H-4), 7.74 (d, 1H, JZ8.5 Hz, H-1),
7.78 (t, 1H, JZ7.4 Hz, H-8), 8.25 (dd, 1H, JZ7.4, 1.1 Hz,
H-7), 8.47 (dd, 1H, JZ7.4, 1.1 Hz, H-9), 15.80 (br s, 1H,
COOH), 13C NMR (DMSO-d6, 100.6 MHz) d 166.1 (s), and
164.8 (s) (COOH, and N–C]O), 146.3 (s), 136.5 (s), 134.8
(s), 130.7 (s), 129.5 (s), 129.1 (s), 132.6 (d, C8), 131.8 (d,
C9), 127.5 (d), 127.0 (d), 126.4 (d), 120.2 (d), 56.6 (d, C6a),
42.4 (t, C6), 33.4 (s, C5), 31.6 (q), and 30.6 (q) (Me-5), 20.6
(q, Me-3). Anal. Calcd for C20H19NO3: C, 74.77; H, 5.92; N,
4.36. Found: C, 74.75; H, 5.92; N, 4.40.
Me-5), 1.51 (s, 3H, Me-5), 1.68 (dd, 1H, JZ12.8, 13.4 Hz,
H-6ax), 2.36 (dd, 1H, JZ13.4, 2.8 Hz, H-6eq), 3.84 (s, 3H,
OMe), 4.91 (dd, 1H, JZ12.8, 2.8 Hz, H-6a), 6.88 (dd, 1H,
JZ8.9, 2.8 Hz, H-2), 6.97 (d, 1H, JZ2.8 Hz, H-4), 7.73 (dd,
1H, JZ7.5, 1.5 Hz, H-Ar), 7.79 (t, 1H, JZ7.5 Hz, H-8),
8.32 (d, 1H, JZ8.9 Hz, H-1), 8.48 (dd, 1H, JZ7.3, 1.5 Hz,
H-Ar); 13C NMR (DMSO-d6, 100.6 MHz) d 165.8 (s), and
165.2 (s) (COOH, and N–C]O), 157.0 (s), 146.3 (s), 138.5
(s), 129.23 (s), 129.16 (s), 126.4 (s), 132.8 (d), 132.0 (d),
126.8 (d), 121.6 (d), 112.7 (d), 112.0 (d), 56.6 (d, C6a), 55.4
(q, OMe), 42.0 (t, C6), 33.9 (s, C5), 31.6 (q), and 30.6 (q)
(Me-5). Anal. Calcd for C20H19NO4: C, 71.22; H, 5.64; N,
4.15. Found: C, 71.22; H, 5.62; N, 4.18.
3.7.4. 1-Ethyl-5,5-dimethyl-5,6,6a,11-tetrahydro-11-
oxoisoindolo[2,1-a]quinoline-10-carboxylic acid (21d).
Yield 1.51 g (45%); mp 199.5–200.5 8C (i-PrOH–DMF);
IR 1744 (COOH), and 1639 (N–C]O) cmK1; EI-MS
(70 eV) m/z (rel intensity): MC 335 (98), 318 (15), 302
(6), 289 (100), 232 (7), 204 (9), 128 (9), 115 (19), 102 (10),
91 (11), 77 (12), 65 (9), 51 (9); 1H NMR (DMSO-d6,
400 MHz) d 1.16 (s, 3H, Me-5), 1.18 (t, 3H, JZ7.5 Hz,
CH2Me), 1.41 (s, 3H, Me-5), 1.74 (dd, 1H, JZ13.4, 8.8 Hz,
H-6ax), 2.46 (dd, 1H, JZ13.4, 5.8 Hz, H-6eq), 2.74 (m, 2H,
CH2Me), 5.21 (dd, 1H, JZ8.8, 5.8 Hz, H-6a), 7.28 (d, 1H,
JZ7.4 Hz, H-Ar), 7.33 (t, 1H, JZ7.4 Hz, H-3), 7.38 (d, 1H,
JZ7.4 Hz, H-Ar), 7.88 (t, 1H, JZ7.5 Hz, H-8), 8.00 (d, 1H,
JZ7.5 Hz, H-7), 8.14 (d, 1H, JZ7.5 Hz, H-9); 13C NMR
(DMSO-d6, 100.6 MHz) d 166.1 (s), and 165.3 (s) (COOH,
and N–C]O), 149.0 (s), 140.0 (s), 138.6 (s), 131.1 (s),
129.7 (s), 128.2 (s), 133.0 (d, C8), 131.4 (d, C9), 127.2 (d),
126.9 (d), 126.8 (d), 123.8 (d), 57.5 (d, C6a), 44.7 (t, C6),
34.3 (s, C5), 31.8 (q), and 29.9 (q) (Me-5), 24.8 (t, CH2CH3),
14.1 (q, CH2CH3). Anal. Calcd for C21H21NO3: C, 75.22; H,
6.27; N, 4.18. Found: C, 75.26; H, 6.28; N, 4.19.
3.7.7. 1-Benzyl-5,5-dimethyl-5,6,6a,11-tetrahydro-11-
oxoisoindolo[2,1-a]quinoline-10-carboxylic acid (21g).
Yield 1.28 g (32%); mp 168–169 8C (i-PrOH–DMF); IR
1726 (COOH), and 1617 (N–C]O) cmK1; EI-MS (70 eV)
m/z (rel intensity): 399 (4), 398 (22), 397 (MC, 72), 380 (2),
354 (4), 353 (16), 352 (31), 351 (100), 338 (5), 336 (6), 322
1
(5), 308 (4), 306 (6), 292 (5), 204 (4), 165 (5), 91 (11); H
NMR (DMSO-d6, 400 MHz) d 1.16 (s, 3H, Me-5), 1.37 (s,
3H, Me-5), 1.67 (dd, 1H, JZ13.4, 9.4 Hz, H-6ax), 2.41 (dd,
1H, JZ13.4, 5.4 Hz, H-6eq), 4.07 and 4.16 (AB, 2H, JZ
15.9 Hz, CH2Ph), 4.91 (dd, 1H, JZ9.4, 5.4 Hz, H-6a), 7.04–
7.09 (m, 4H, H-Ar), 7.16 (t, 2H, JZ7.4 Hz, H-Ar), 7.25
(t, 1H, JZ7.6 Hz, H-Ar), 7.39 (br d, 1H, JZ7.5 Hz, H-Ar),
7.83 (t, 1H, JZ7.6 Hz, H-Ar), 7.94 (d, 1H, JZ7.6 Hz,
H-Ar), 8.06 (d, 1H, JZ7.6 Hz, H-9); 13C NMR (DMSO-d6,
100.6 MHz) d 166.0 (s), and 165.7 (s) (COOH, and
N–C]O), 148.8 (s), 140.8 (s), 140.4 (s), 136.6 (s), 133.0
(d), 131.5 (s), 131.3 (d), 130.1 (s), 128.9 (2C, d), 128.8 (d),
128.4 (2C, d), 128.2 (s), 127.1 (d), 126.7 (d), 126.1 (d),
124.4 (d), 57.4 (d, C6a), 34.4 (s, C5), 38.6 (t, CH2Ph), 44.6
(t, C6), 31.8 (q), and 30.0 (q) (Me-5). Anal. Calcd for
C26H23NO3: C, 78.59; H, 5.79; N, 3.53. Found: C, 78.63; H,
5.78; N, 3.56.
3.7.5. 1-Methoxy-5,5-dimethyl-5,6,6a,11-tetrahydro-11-
oxoisoindolo[2,1-a]quinoline-10-carboxylic acid (21e).
Yield 1.15 g (34%); mp 248–250 8C (i-PrOH–DMF); IR
1723 (COOH), and 1628 (N–C]O) cmK1; EI-MS (70 eV)
m/z (rel intensity): MC 337 (100), 302 (25), 304 (12), 293
(82), 278 (9), 263 (20), 248 (18), 135 (16), 220 (9), 204 (13),
3.7.8. 1,3,5,5-Tetramethyl-5,6,6a,11-tetrahydro-11-oxo-
isoindolo[2,1-a]quinoline-10-carboxylic acid (21h).
Yield 2.04 g (61%); mp 220–221 8C (i-PrOH–DMF); IR
1718 (COOH, and N–C]O) cmK1; EI-MS (70 eV) m/z (rel
intensity): MC 335 (100), 320 (18), 302 (16), 289 (76), 276
(11), 246 (11), 235 (13), 218 (3), 204 (3), 172 (4), 137 (5),
1
152 (9), 139 (20), 102 (25), 91 (27), 73 (30), 65 (19); H
NMR (DMSO-d6, 400 MHz) d 1.29 (s, 3H, Me-5), 1.38 (s,
3H, Me-5), 1.50 (dd, 1H, JZ13.1, 11.7 Hz, H-6ax), 2.45
(dd, 1H, JZ13.1, 3.3 Hz, H-6eq), 3.84 (s, 3H, OMe), 5.16
(dd, 1H, JZ11.7, 3.3 Hz,-6a), 7.04 (d, 1H, JZ7.7 Hz,
H-Ar), 7.13 (d, 1H, JZ7.7 Hz,-Ar), 7.29 (t, 1H, JZ7.7 Hz,
H-3), 7.85 (t, 1H, JZ7.7 Hz, H-8), 8.01 (d, 1H, JZ7.7 Hz,
H-7), 8.13 (d, 1H, JZ7.7 Hz, H-9); 13C NMR (DMSO-d6,
100.6 MHz) d 165.2 (s), and 165.1 (s) (COOH, and
N–C]O), 152.7 (s), 148.2 (s), 140.2 (s), 129.4 (s), 128.8
(s), 121.8 (s), 132.8 (d, C8), 131.9 (d, C9), 127.6 (d), 127.1
(d), 118.5 (d), 110.7 (d), 56.8 (OMe-1), 56.0 (d, C6a), 45.2 (t,
C6), 34.1 (s, C5), 32.3 (q), and 30.1 (q) (Me-5). Anal. Calcd
for C20H19NO4: C, 71.22; H, 5.64; N, 4.15. Found: C, 71.18;
H, 5.69; N, 4.15.
1
128 (7), 115 (10), 91 (5); H NMR (CDCl3, 400 MHz) d
1.29 (s, 3H, Me-5), 1.44 (s, 3H, Me-5), 1.73 (dd, 1H, JZ
13.3, 10.1 Hz, H-6ax), 2.36 (s, 3H, Me-Ar), 2.38 (s, 3H,
Me-Ar), 2.40 (dd, 1H, JZ13.3, 4.7 Hz, H-6eq), 4.94 (dd,
1H, JZ10.1, 4.7 Hz, H-6a), 7.03 (br s, 1H, H-Ar), 7.09 (br s,
1H, H-Ar), 7.75–7.80 (m, 2H, H-Ar), 8.45 (dd, JZ6.1, 2.5,
H-Ar), 15.65 (br s, 1H, COOH); 13C NMR (DMSO-d6,
100.6 MHz) d 165.6 (s), and 165.3 (s) (COOH, and
N–C]O), 148.6 (s), 139.2 (s), 136.0 (s), 132.4 (s), 129.6
(s), 129.2 (s), 128.6 (s), 132.8 (d, C8), 131.6 (d, C9), 129.7
(d), 126.8 (d), 124.5 (d), 57.4 (d, C6a), 45.2 (t, C6), 34.0 (s,
C5), 32.1 (q), and 30.1 (q) (Me-5), 20.8 (q), and 19.8 (q)
(Me-1 and Me-3). Anal. Calcd for C21H21NO3: C, 75.22; H,
6.27; N, 4.18. Found: C, 75.24; H, 6.23; N, 4.20.
3.7.6. 3-Methoxy-5,5-dimethyl-5,6,6a,11-tetrahydro-11-
oxoisoindolo[2,1-a]quinoline-10-carboxylic acid (21f).
Yield 2.43 g (72%); mp 228–229.5 8C (i-PrOH–DMF); IR
1732 (COOH), and 1627 (N–C]O) cmK1; EI-MS (70 eV)
m/z (rel intensity): MC 337 (100), 322 (30), 304 (7), 293
(24), 278 (18), 262 (4), 205 (4), 191 (3), 139 (3), 115 (2),
102 (2), 91 (2); 1H NMR (CDCl3, 400 MHz) d 1.44 (s, 3H,
3.7.9. 3-Isopropyl-5,5-dimethyl-5,6,6a,11-tetrahydro-11-
oxoisoindolo[2,1-a]quinoline-10-carboxylic acid (21i).
Yield 2.34 g (67%); mp 223.5–224.5 8C (i-PrOH–DMF);
IR 1708 (COOH, and N–C]O) cmK1; EI-MS (70 eV) m/z

F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
4111
(rel intensity): MC 349 (92), 334 (100), 316 (8), 305 (40),
290 (11), 273 (5), 115 (6), 43 (11); 1H NMR (CDCl3,
400 MHz) d 1.20 (d, 6H, JZ6.9 Hz, CHMe2), 1.37 (s, 3H,
Me-5), 1.45 (s, 3H, Me-5), 1.57 (t, 1H, JZ12.9 Hz, H-6ax),
2.49 (dd, 1H, JZ13.1, 2.6 Hz, H-6eq), 2.90 (sept, 1H, JZ
6.9 Hz, CHMe2), 5.15 (dd, 1H, JZ12.7, 2.2 Hz, H-6a), 7.19
(dd, 1H, JZ8.5, 1.8 Hz, H-2), 7.40 (d, 1H, JZ1.8 Hz, H-4),
7.85 (t, 1H, JZ7.6 Hz, H-8), 8.01 (br d, 1H, JZ7.6 Hz,
H-7), 8.11 (br d, 1H, JZ7.6 Hz, H-9), 8.16 (d, 1H, JZ
8.5 Hz, H-1); 13C NMR (DMSO-d6, 100.6 MHz) d 166.1 (s),
and 165.3 (s) (COOH, and N–C]O), 146.3 (s), 146.0 (s),
136.6 (s), 133.0 (d), 131.9 (d), 131.1 (s), 129.4 (s), 129.2 (s),
126.8 (d), 125.4 (d), 124.3 (d), 120.5 (d), 56.6 (d, C6a), 33.7
(s, C5), 42.2 (t, C6), 33.4 (d, CHMe2), 31.8 (q), and 30.8 (q)
(Me-5), 24.1 (q), and 24.0 (q) (CHMe2). Anal. Calcd for
C22H23NO3: C, 75.65; H, 6.59; N, 4.01. Found: C, 75.68; H,
6.62; N, 4.03.
(dd, 1H, JZ5.9, 2.7 Hz, H-Ar); 13C NMR (DMSO-d6,
100.6 MHz) d 167.9 (s), and 165.1 (s) (C]O), 158.2 (s),
146.0 (s), 132.9 (d), 132.1 (d), 130.6 (d), 129.0 (s), 128.8 (s),
127.9 (s), 127.4 (d), 126.5 (2C, d), 119.9 (t, CH2]), 114.5
(2C, d), 61.7 (d, C3), 55.5 (q, OMe), 34.0 (t, –CH2–). Anal.
Calcd for C19H17NO4: C, 70.59; H, 5.26; N, 4.33. Found: C,
70.62; H, 5.24; N, 4.30.
3.9. 5-Methyl-5,6-dihydro-10-carboxyisoindolo[2,1-a]-
quinoline-11-ones (23a–e). Typical procedure
Corresponding adduct 14 (0.01 mol), the mixture of 85%
H3PO4 and 96% H2SO4 (45 mL, 3:1 in volume) were stirred
at 100–120 8C for 1 h (monitoring by TLC). At the end of
the reaction, the mixture was diluted with water (200 mL).
The obtained precipitate was filtered off, washed with cold
water (5!80 mL) and dried in air. Then the crude product
was purified by recrystallization to give desired isoindolo-
quinolines 23 as colorless crystals.
3.8. 1-Allyl-3-oxo-2-arylisoindolo-7-carboxylic acids
(22a,b). Typical procedure
3.9.1. 5-Methyl-5,6,6a,11-tetrahydro-11-oxoisoindolo-
[2,1-a]quinoline-10-carboxylic acid (23a). Ratio of
isomers A/Bw4/1; yield 1.52 g (52%); mp 185.5–186 8C
(i-PrOH–DMF); IR 1728 (COOH), and 1623 (N–
C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC 293
(54), 278 (11), 264 (5), 250 (24), 249 (100), 234 (26), 232
(12), 220 (8), 234 (26), 232 (12), 217 (7), 204 (20), 131 (6),
117 (7), 102 (8), 91 (7), 77 (14); 1H NMR (CDCl3,
200 MHz) isomer A d 1.53 (d, 3H, JZ7.0 Hz, Me-5), 1.89
(dt, 1H, JZ12.8, 5.8 Hz, H-6ax), 2.41 (ddd, 1H, JZ12.8,
2.8, 1.2 Hz, H-6eq), 3.32 (ddd, 1H, JZ7.0, 5.8, 1.2 Hz,
H-5), 4.93 (dd, 1H, JZ12.8, 2.8 Hz, H-6a), 7.15–7.50 (m,
3H, H-Ar), 7.70–7.85 (m, 2H, H-Ar), 8.35–8.55 (m, 2H,
H-Ar); 13C NMR (DMSO-d6, 100.6 MHz) d 166.2 (s), and
165.4 (s) (COOH, and N–C]O), 146.1 (s), 134.2 (s), 132.3
(s), 129.5 (s), 128.8 (s), 133.0 (d, C8), 131.6 (d, C9), 127.8
(d), 126.6 (d), 126.5 (d), 125.4 (d), 120.2 (d), 59.4 (d, C6a),
36.0 (t, C6), 30.8 (d, C5), 20.7 (q, Me-5); 1H NMR (CDCl3,
200 MHz) isomer B d 1.47 (d, 3H, JZ6.7 Hz, Me-5), 1.48
(ddd, 1H, JZ13.2, 12.8, 11.0 Hz, H-6A), 2.73 (ddd, 1H, JZ
13.2, 5.8, 2.8 Hz, H-6B), 3.32 (ddd, 1H, JZ11.0, 6.7,
5.8 Hz, H-5), 4.84 (dd, 1H, JZ12.8, 2.8 Hz, H-6a), 7.15–
7.50 (m, 3H, H-Ar), 7.70–7.85 (m, 2H, H-Ar), 8.35–8.55 (m,
2H, H-Ar); 13C NMR (DMSO-d6, 100.6 MHz) d 166.4 (s),
and 165.4 (s) (COOH, and N–C]O), 146.5 (s), 134.0 (s),
132.9 (s), 129.5 (s), 128.9 (s), 133.0 (d, C8), 131.5 (d, C9),
129.8 (d), 126.6 (d), 126.5 (d), 125.3 (d), 120.1 (d), 55.2 (d,
C6a), 33.5 (t, C6), 30.3 (d, C5), 24.0 (q, Me-5). Anal. Calcd
for C18H15NO3: C, 73.72; H, 4.78; N, 4.78. Found: C, 73.53;
H, 5.00; N, 4.75.
A mixture of corresponding adduct 14a,d (0.01 mol) and
85% H3PO4 (40 mL) was stirred at 65 8C for 1.5 h
(monitoring by TLC). At the end of the reaction, the
mixture was diluted with water (200 mL). The obtained
precipitate was filtered off, washed with cold water (5!
80 mL) and dried in air. Then the crude product was purified
by recrystallization to give desired products 22a,b as
colorless crystals.
3.8.1. 1-Allyl-3-oxo-2-phenyl-2,3-dihydro-1H-isoindole-
4-carboxylic acid (22a). Yield 1.52 g (52%); mp 123–
124 8C (ethyl acetate–hexane); IR 1782 (COOH), and 1652
(N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
293 (4), 252 (100), 209 (20), 180 (23), 152 (14), 104 (14), 89
1
(5), 77 (68), 57 (8), 51 (21), 40 (33); H NMR (CDCl3,
400 MHz) d 2.61 (ddd, 1H, JZ14.3, 7.8, 6.2 Hz, H-30A),
2.80 (ddd, 1H, JZ14.8, 7.8, 3.3 Hz, H-30B), 4.85 (dd, 1H,
JZ16.9, 1.0 Hz, H-10trans), 5.00 (br d, 1H, JZ10.1 Hz,
H-10cis), 5.26 (ddd, 1H, JZ16.9, 10.1, 7.8 Hz, H-20), 5.40
(dd, 1H, JZ6.2, 3.3 Hz, H-3), 7.39 (m, 1H, H-Ar), 7.50–
7.55 (m, 4H, H-Ar), 7.76–7.81 (m, 2H, H-Ar), 8.47 (dd, JZ
6.7, 2.0 Hz, H-Ar); 13C NMR (DMSO-d6, 100.6 MHz) d
167.8 (s), and 165.2 (s) (C]O), 146.0 (s), 135.4 (s), 133.1
(d), 131.8 (d), 130.5 (d), 129.27 (2C, d), 129.24 (s), 128.7
(s), 127.2 (d), 127.1 (d), 124.8 (2C, d), 119.9 (t, CH2]),
61.2 (d, C3), 34.0 (t, –CH2–). Anal. Calcd for C18H15NO3:
C, 73.72; H, 5.12; N, 4.78. Found: C, 73.75; H, 5.16;
N, 4.81.
3.8.2. 1-Allyl-3-oxo-2-(40-methoxyphenyl)-2,3-dihydro-
1H-isoindole-4-carboxylic acid (22b). Yield 1.97 g
(61%); mp 124.5–126 8C (ethyl acetate–chloroform); IR
1723 (COOH, and N–C]O) cmK1; EI-MS (70 eV) m/z (rel
intensity): MC 323 (23), 282 (100), 264 (2), 238 (12), 210
(14), 195 (3), 167 (10), 141 (3), 128 (4), 92 (10), 77 (16); 1H
NMR (CDCl3, 400 MHz) d 2.56 (ddd, 1H, JZ14.4, 8.0,
5.9 Hz, H-30A), 2.77 (ddd, 1H, JZ14.4, 6.0, 3.5 Hz, H-30B),
3.84 (s, 3H, OMe), 4.85 (dd, 1H, JZ16.8, 1.2 Hz,
H-10trans), 4.97 (br d, 1H, JZ10.0 Hz, H-10cis), 5.32
(dddd, 1H, JZ16.8, 10.0, 8.0, 6.0 Hz, H-20), 5.31 (dd, 1H,
JZ5.9, 3.5 Hz, H-3), 6.99 (d, 2H, JZ8.9 Hz, H-Ar), 7.38
(d, 2H, JZ8.9 Hz, H-Ar), 7.71–7.76 (m, 2H, H-Ar), 8.38
3.9.2. 1,5-Dimethyl-5,6,6a,11-tetrahydro-11-oxoiso-
indolo[2,1-a]quinoline-10-carboxylic acid (23b). Ratio
of isomers A/Bw4.5/1; yield 1.50 g (49%); mp 142.5–
143 8C (i-PrOH–DMF); IR 1723 (COOH, and
N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity): MC
307 (29), 289 (7), 278 (4), 266 (100), 261 (59), 222 (8), 165
1
(8), 128 (6), 118 (15), 91 (47), 77 (19), 65 (41); H NMR
(CDCl3, 200 MHz) isomer A d 1.31 (d, 3H, JZ6.9 Hz,
Me-5), 1.59 (dt, 1H, JZ13.5, 9.9 Hz, H-6ax), 2.41 (s, 3H,
Me-1), 2.77 (ddd, 1H, JZ13.5, 6.6, 4.9 Hz, H-6eq), 3.28
(ddd, 1H, JZ13.5, 6.9, 6.6 Hz, H-5), 4.94 (dd, 1H, JZ9.9,
4.9 Hz, H-6a), 7.19–7.30 (m, 3H, H-Ar), 7.75–7.85 (m, 2H,

4112
F. I. Zubkov et al. / Tetrahedron 61 (2005) 4099–4113
H-7 and H-8), 8.48 (m, 1H, H-9); 13C NMR (DMSO-d6,
100.6 MHz) d 167.5 (s), and 167.0 (s) (COOH, and
N–C]O), 149.9 (s), 137.0 (s), 134.2 (d), 134.0 (s), 133.2
(s), 132.7 (d), 130.4 (s), 130.4 (d), 128.9 (s), 128.2 (d), 128.0
(d), 126.2 (d), 60.6 (d, C6a), 38.2 (t, C6), 32.1 (d, C5), 22.5
(q, Me-5), 20.5 (q, Me-1). Anal. Calcd for C19H17NO3: C,
74.26; H, 4.56; N, 5.54. Found: C, 74.05; H, 5.63; N, 4.43.
(q, Me-5). Anal. Calcd for C19H17NO4: C, 70.59; H, 5.26; N,
4.33. Found: C, 70.60; H, 5.28; N, 4.37.
3.9.5. 1,2,5-Trimethyl-5,6,6a,11-tetrahydro-11-oxoiso-
indolo[2,1-a]quinoline-10-carboxylic acid (23e). Ratio
of isomers A/Bw6/1; yield 1.77 g (55%); mp 220–222 8C
(i-PrOH–DMF); IR 1715 (COOH, and N–C]O) cmK1
;
EI-MS (70 eV) m/z (rel intensity): MC 321 (72), 304 (7),
275 (100), 262 (12), 246 (5), 232 (10), 204 (6), 158 (3), 115
3.9.3. 1-Methoxy-5-methyl-5,6,6a,11-tetrahydro-11-
oxoisoindolo[2,1-a]quinoline-10-carboxylic acid (23c).
Ratio of isomers A/Bw3.5/1; yield 1.03 g (32%); mp
207–209 8C (heptane–chloroform); IR 1723 (COOH), and
1628 (N–C]O) cmK1; EI-MS (70 eV) m/z (rel intensity):
1
(9), 91 (7); H NMR (CDCl3, 400 MHz) isomer A d 1.27
(d, 3H, JZ7.3 Hz, Me-5), 1.58 (ddd, 1H, JZ13.5, 9.7,
9.2 Hz, H-6ax), 2.24 (s, 3H, Me-Ar), 2.35 (s, 3H, Me-Ar),
2.74 (ddd, 1H, JZ13.5, 6.4, 5.1 Hz, H-6eq), 3.24 (ddd, 1H,
JZ9.2, 7.3, 6.4 Hz, H-5), 4.95 (dd, 1H, JZ9.7, 5.1 Hz,
H-6a), 7.15 (s, 2H, H-3 and H-4), 7.78–7.81 (m, 2H, H-8 and
H-9), 8.46 (d, 1H, JZ7.4 Hz, H-9); 13C NMR (DMSO-d6,
100.6 MHz) d 166.1 (s), and 165.4 (s) (COOH, and
N–C]O), 148.9 (s), 135.8 (s), 133.2 (s), 133.0 (d), 132.5
(s), 131.9 (d), 131.5 (s), 129.8 (s), 128.3 (s), 128.2 (d), 126.8
(d), 124.5 (d), 59.6 (d, C6a), 38.5 (t, C6), 31.1 (d, C5), 21.5
(q), 20.0 (q), 16.7 (q) (Me-5, Me-1, Me-2). Anal. Calcd for
C20H19NO3: C, 74.77; N, 5.92; H, 4.36. Found: C, 74.75; N,
5.96; H, 4.39.
M
C 323 (100), 306 (26), 279 (85), 249 (23), 234 (19), 220
(14), 204 (13), 191 (9), 165 (5), 153 (6), 132 (5), 103 (5), 77
(9), 36 (6), 28 (10); 1H NMR (CDCl3, 400 MHz) isomer A d
1.37 (d, 3H, JZ6.9 Hz, Me-5), 1.44 (td, 1H, JZ13.4,
11.3 Hz, H-6ax), 2.73 (ddd, 1H, JZ13.4, 6.5, 3.8 Hz,
H-6eq), 3.27 (ddq, 1H, JZ11.3, 6.9, 6.5 Hz, H-5), 3.95 (s,
3H, OMe), 4.84 (dd, 1H, JZ11.3, 3.8 Hz, H-6a), 6.96 (br d,
1H, JZ8.0 Hz, H-2), 7.01 (dd, 1H, JZ8.0, 1.0 Hz, H-4),
7.29 (t, 1H, JZ8.0 Hz, H-3), 7.70–7.80 (m, 2H, H-Ar), 8.45
(dd, 1H, JZ7.2, 1.5 Hz, H-9); 13C NMR (DMSO-d6,
100.6 MHz) d 165.3 (s), and 165.2 (s) (COOH, and
N–C]O), 152.9 (s), 148.2 (s), 136.2 (s), 132.94 (d),
132.08 (d), 129.39 (s), 128.67 (s), 127.6 (d), 127.1 (d), 122.8
(s), 119.4 (d), 111.0 (d), 59.2 (d, C6a), 56.1 (OMe), 38.8 (t,
C6), 30.8 (d, C5), 21.3 (q, Me-5); 1H NMR (CDCl3,
400 MHz) isomer B d 1.42 (d, 3H, JZ7.0 Hz, Me-5), 2.04
(ddd, 1H, JZ13.5, 8.4, 6.0 Hz, H6A), 2.29 (ddd, 1H, JZ
13.5, 6.0, 5.7 Hz, H-6B), 2.99 (ddq, 1H, JZ7.0, 6.0, 5.7 Hz,
H-5), 3.96 (s, 3H, OMe), 4.92 (dd, 1H, JZ8.4, 6.0 Hz,
H-6a), 6.92 (br d, 1H, JZ7.8, H-2), 6.98 (br d, 1H, JZ
7.8 Hz, H-4), 7.30 (t, 1H, JZ7.8 Hz, H-3), 7.70–7.80 (m,
2H, H-Ar), 8.45 (dd, 1H, JZ7.2, 1.5 Hz, H-9); 13C NMR
(DMSO-d6, 100.6 MHz) d 165.9 (s), and 165.2 (s) (COOH,
and N–C]O), 152.9 (s), 148.5 (s), 138.0 (s), 133.06 (d),
131.98 (d), 129.34 (s), 128.83 (s), 127.8 (d), 127.3 (d), 122.8
(s), 119.6 (d), 110.9 (d), 56.4 (d, C6a), 56.0 (OMe), 37.2 (t,
C6), 29.6 (d, C5), 22.4 (q, Me-5). Anal. Calcd for
C19H17NO4: C, 70.59; H, 5.26; N, 4.33. Found: C, 70.62;
H, 5.27; N, 4.33.
Acknowledgements
The authors are grateful for the financial support by the
Russian Foundation for Basic Research (grant no. 01-03-32
844 and 04-03-32 433). Also the authors would like to thank
Dr. K. Paulvannan, Sunesis Pharmaceuticals, Inc. for the
useful discussion during the preparation of this manuscript.
References and notes
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222 8C (i-PrOH–DMF); IR 1707 (COOH), and 1615
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323 (100), 308 (21), 290 (5), 279 (53), 264 (45), 250 (5), 236
(8), 221 (8), 204 (5), 191 (9), 166 (3), 104 (3), 91 (3), 77 (4);
1H NMR (CDCl3, 400 MHz) isomer A d 1.45 (d, 3H, JZ
6.7 Hz, Me-5), 1.47 (q, 1H, JZ12.9, 12.4, 12.0 Hz, H-6ax),
2.71 (ddd, 1H, JZ12.9, 5.7, 2.0 Hz, H-6eq), 3.28 (ddq, 1H,
JZ12.0, 6.7, 5.7 Hz, H-5), 3.82 (s, 3H, OMe), 4.83 (dd, 1H,
JZ12.4, 2.0 Hz, H-6a), 6.84 (dd, 1H, JZ9.0, 1.6 Hz, H-2),
6.94 (d, 1H, JZ1.6 Hz, H-4), 7.75–7.80 (m, 2H, H-Ar), 8.32
(d, 1H, JZ9.0 Hz, H-1), 8.43 (dd, 1H, JZ6.7, 0.9 Hz, H-9),
15.70 (br s, 1H, COOH); 13C NMR (DMSO-d6, 100.6 MHz)
d 165.7 (s), and 165.2 (s) (COOH, and N–C]O), 156.8 (s),
146.4 (s), 145.9 (s), 134.1 (s), 129.0 (s), 127.4 (s), 132.8 (d,
C8), 132.0 (d, C9), 126.7 (d), 121.4 (d), 113.1 (d), 112.1 (d),
59.5 (MeO-3), 55.4 (d, C6a), 36.0 (t, C6), 31.0 (d, C5), 20.7
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