1,7-Electrocyclization reactions of stabilized α,β:γ,δ-unsaturated azomethine ylides

Article abstract of DOI:10.1016/j.tet.2006.03.088

Stabilized α,β:γ,δ-unsaturated azomethine ylides were generated by the deprotonation of isoquinolinium salts. 1,7-Electrocyclization of these dipoles, followed by a 1,5-hydrogen shift, gives tetrahydro[5,6]azepino[2,1-a]isoquinolines.

Full text of DOI:10.1016/j.tet.2006.03.088

Tetrahedron 62 (2006) 5725–5735
1,7-Electrocyclization reactions of stabilized a,b:g,d-unsaturated
azomethine ylides
a
b
b
a
c
´
´
´
´
´
´
´
*
Judit Toth, Andras Dancso, Gabor Blasko, Laszlo TTke, Paul W. Groundwater
a,
´
and Miklos Nyerges
aResearch Group of the Hungarian Academy of Sciences, Department of Organic Chemical Technology,
Technical University of Budapest, H-1521 Budapest, PO Box 91, Hungary
bEGIS Pharmaceuticals Ltd, H-1475 Budapest, PO Box 100, Hungary
cSunderland Pharmacy School—Drug Deisgn and Molecular Modelling, University of Sunderland, Sunderland SR1 3SD, UK
Received 24 January 2006; revised 28 February 2006; accepted 23 March 2006
Available online 2 May 2006
Abstract—Stabilized a,b:g,d-unsaturated azomethine ylides were generated by the deprotonation of isoquinolinium salts. 1,7-Electrocycli-
zation of these dipoles, followed by a 1,5-hydrogen shift, gives tetrahydro[5,6]azepino[2,1-a]isoquinolines.
Ó 2006 Elsevier Ltd. All rights reserved.
Ph
1. Introduction
R
N
R = Me,
E = H
For many years 1,3-dipoles have been used extensively in the
construction of five-membered heterocyclic rings via their
cycloadditions with suitable dipolarophiles1 and by the 1,5-
electrocyclization reactions of a,b-unsaturated 1,3-dipoles.2
More recently, the electrocyclization of diene-conjugated
1,3-dipolar intermediates has provided a powerful general
synthetic route to seven-membered heterocyclic ring sys-
tems.3 We have been concerned for some years with synthetic
and mechanistic aspects of these reactions and, in particular,
with the cyclizations of azomethine ylides to give azepines.4
During these studies we have found significant differences
between the reactivity of a,b:g,d-unsaturated, non-stabilized
1 (E¼H) and a,b:g,d-unsaturated, ester-stabilized azo-
methine ylides 1 (E¼CO2Et). The former dipoles react via
a 1,7-electrocyclization,5 followed by a [1,5]-hydrogen shift
to give dihydroazepines 2, while the latter give other products
(3 or 4) via novel rearrangements (Scheme 1).6,7
E
Ph
N
Ph
CH3
1
2
R = H,
E = CO2Et
R = Me, E = CO2Et
Ph
Ph
CH3
N
NH2
CO2Et
Ph
Ph
EtO2C
N
O
CH3
3
4
Scheme 1.
2. Results and discussion
We recently published the first examples of the 1,7-electro-
cyclizations of an azomethine ylide onto a nitro group,
producing indazole-N-oxides after the ring contraction of
the unstable oxadiazepine intermediates.8 As a continuation
of these studies we have now examined the reactivity of
somea,b:g,d-unsaturated, ester-stabilizedazomethineylides
generated by the deprotonation of iminium salts derived
from 3,4-dihydroisoquinolines.9
The synthesis of the dipole precursors was carried out ac-
cording to the Bischler–Napieralski procedure10 by cycliza-
tion of amides 6a–b in the presence of POCl3 and resulted in
the formation of 3,4-dihydroisoquinolines 7a–b. Subsequent
reaction with different bromoalkyl derivatives, in anhydrous
ether, gave the quaternary salts 8 (Scheme 2, Table 1).
Reacting the isoquinolinium salts 8a–j with triethylamine, at
ambient temperature in dry methanol, leads to the forma-
tion of 8-substituted-2,3-dimethoxy-13-phenyl-5,6,8,14a-
tetrahydrobenz[5,6]azepino[2,1-a]isoquinolines 11a–j via
* Corresponding author. Tel.: +361 4632213; fax: +361 463648;
e-mail: mnyerges@mail.bme.hu
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.088

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J. Toth et al. / Tetrahedron 62 (2006) 5725–5735
5726
RO
RO
We next studied the influence of steric restrictions on the
RO
i
ii
ethenyl side chain on the course of 1,7-electrocyclization re-
action. The synthesis of the requisite precursors commenced
with the conversion of the amides 12, derived by coupling 2-
(3,4-dimethoxyphenyl)ethylamine 5a with fluorenylidene12
and naphthoic acid chlorides, to the dihydroisoquinolines 13.
NH
NH2
RO
O
Ph
Ph
5aR = Me
5bR = Et
6a R = Me
6b R = Et
RO
RO
RO
RO
The cyclized products 13a–b were obtained in isolated
yields greater than 70%, thus showing that the replacement
of the side-chains had no affect on the outcome of the cycli-
zation reaction (Scheme 4).
iii
Br
N
N
R1
Ph
Ph
7a R = Me
7bR = Et
8
Ph
Ph
The alkylation of 13a with three bromoalkyl derivatives, in
anhydrous ether, gave the quaternary salts 14a–c, the reac-
tion of which, with triethylamine at room temperature in
methanol, provided the expected hexacyclic products 15a–c.
These novel compounds were isolated in acceptable yields
after column chromatography (Scheme 5).
Scheme 2. Reagents and conditions: (i) Ph2C]CHCOCl, NaOH, Et2O,
H2O, rt; (ii) POCl3, toluene, reflux and (iii) R1CH2Br, Et2O, rt.
Table 1
Entry
R
R1
Product Yield (%) Product Yield (%)
1
2
3
4
5
6
7
8
9
10
Me –CO2Me
Et –CO2Me
Me Ph–
8a
8b
8c
8d
8e
8f
100
100
98
96
95
11a
11b
11c
11d
11e
11f
11g
11h
11i
83
86
77
82
53
50
81
80
85
73
MeO
MeO
MeO
Br
R
H
N
N
R
Et Ph–
MeO
i
H
Me CH2]CH–
Et CH2]CH–
Me PhCO–
Et PhCO–
Me 3-MeOPhCO– 8i
Me 2-CNPh– 8j
ii
97
13a
8g
8h
100
100
100
99
11j
15a R = -CO2Me (49 %)
15b R = -Ph (46 %)
14a R = -CO2Me (100%)
14b R = -Ph (97 %)
14c R = -CH=CH2 (98 %)
azomethine ylide intermediates 9a–j. The benzazepinoiso-
quinolines could be isolated in moderate to good yields by
simple filtration. In this reaction the azomethine ylides are
produced by dehydrohalogenation of the isoquinolinium
salts,11 which leads, via a 1,7-electrocyclization to the
azepines 10, and finally, by a [1,5]-hydrogen shift, to the
products 11a–j (Scheme 3, Table 1). The relative stereo-
chemistry of the tetracycles 11a–j was deduced by NOE
studies.
15c R = -CH=CH2 (44 %)
Scheme 5. Reagents and conditions: (i) R1CH2Br, Et2O, rt; (ii) Et3N,
MeOH, rt.
The reaction of quaternary salt 16, prepared from isoquino-
line 13b and ethyl bromoacetate, with triethylamine or with
other bases such as DBU, DABCO, or KOBut and in differ-
ent solvents, did not give the expected cyclized product—
only the dihydroisoquinoline 13b was isolated from the
complex reaction mixture formed (Scheme 6).
RO
RO
RO
RO
Br
i
R1
R1
N
N
These experiments show the scope and limitations of our
strategy for the construction of the azepine ring system via
the 1,7-electrocyclization of these azomethine ylides. The re-
actions with the diphenylethenyl side chains proceeded in
good to excellent yield, depending upon the electron-with-
drawing ability of the substituent on the azomethine ylide.
The steric restrictions caused by the additional bond between
the two phenyl groups in the dipoles derived from 14a–c
resulted in significant decrease in the yields of the electro-
cyclization products 15a–c and the rigid nature of the naph-
thalene side chain makes the reaction of 16 impossible.
Ph
Ph
Ph
9
8
RO
RO
RO
RO
R1
N
R1
H
N
H
Ph
Ph
10
11
In order to extend the scope of this reaction we have used
a different method for the generation of a,b:g,d-unsaturated
Scheme 3. Reagents and conditions: (i) Et3N, MeOH, rt.
R =
MeO
MeO
MeO
i
NH
5a
N
MeO
O
R
R
12a (92 %)
12b (61 %)
a
13a (70 %)
13b (75 %)
b
Scheme 4. Reagents and conditions: (i) RCOCl, NaOH, Et2O, H2O, rt and (ii) POCl3, toluene, reflux.

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J. Toth et al. / Tetrahedron 62 (2006) 5725–5735
5727
MeO
MeO
MeO
MeO
MeO
MeO
Br
CO2Et
N
N
CO2Et
ii
N
i
13b
16 (100 %)
17
Scheme 6. Reagents and conditions: (i) EtO2CCH2Br, Et2O, rt and (ii) Et3N, MeOH, rt.
CH3O
CH3O
CH3O
CH3O
CH3O
CH3O
Ar
H
N
ii
i
N
NH
Ph
H
Ph
Ph
Ph
Ph
11
7a
18
Scheme 7. Reagents and conditions: (i) NaBH4, EtOH and (ii) ArCHO, xylene, reflux.
azomethine ylides 9 where R1 is derived from an aromatic
aldehyde. This method was efficiently used by Grigg and
co-workers in the synthesis of a pyrrolo[2,1-a]isoquinoline
via a 1,5-electrocyclization.13 The reduction of 7a with
sodiumborohydridegavethetetrahydroisoquinoline18, which
on refluxing with xylene, reacted slowly with various aro-
matic aldehydes furnishing tetrahydrobenz[5,6]azepino[2,1-
a]isoquinolines 11c, 11k, 11l and 11m in low yield
(Scheme 7, Table 2).
3.1.1. N-[2-(30,40-Dimethoxyphenyl)ethyl]-3,3-diphenyl-
2-propenamide (6a). 2-(3,4-Dimethoxy-phenyl)ethyl amine
5a (7.27 g, 40 mmol) was dissolved in ether (40 ml) and 10%
aqueous sodium hydroxide (1.6 g, 40 mmol in 15 ml water)
was added at 0 ꢀC. A solution of b-phenylcinnamoyl chloride
(9.97 g, 40 mmol) in ether (30 ml) was added dropwise. After
4 h stirring at room temperature the precipitated product
was filtered off and washed with water then ether and dried
in air to give the product as a white powder (10.70 g, 69%),
mp 162–163 ꢀC; [Found: C, 77.7; H, 6.5; N, 3.5.
1
Table 2
C25H25NO3 requires C, 77.5; H, 6.5; N, 3.6%]; H NMR
(250 MHz, CDCl3): 7.35–7.21 (m, 10H, Ar–H), 6.73 (d,
1H, J¼8.0 Hz, H-50), 6.57 (s, 1H, H-20), 6.51 (d, 1H,
J¼8.0 Hz, H-60), 6.35 (s, 1H, H-2), 5.35 (br s, 1H, NH),
3.85 (s, 3H, OMe), 3.83 (s, 3H, OMe), 3.33 (t, 2H,
J¼7.2 Hz, CH2), 2.48 (t, 2H, J¼7.2 Hz, NCH2); 13C NMR
(63 MHz, CDCl3): 166.7 (quat.), 149.4 (quat.), 148.8
(quat.), 147.5 (quat.), 140.6 (quat.), 138.3 (quat.), 131.1
(quat.), 129.3 (2ꢁCH), 128.8 (CH), 128.4 (2ꢁCH), 128.35
(CH), 128.3 (2ꢁCH), 127.8 (2ꢁCH), 122.5 (CH), 120.4
(CH), 111.6 (CH), 111.2 (CH), 55.8 (CH3), 55.7 (CH3),
40.4 (CH2), 34.6 (CH2); IR (KBr, cmꢂ1): 3286, 3057,
2962, 2925, 2835, 1639, 1614, 1547, 1518, 1464, 1442,
1417, 1386, 1356, 1287, 1270, 1225, 1160, 1151, 1137, 1028.
Entry
Ar
Reaction time (h)
Product
Yield (%)
1
2
3
4
Ph–
4-ClPh–
4-MeO–Ph–
3,4-MeO–Ph–
16
12
30
48
11c
11k
11l
24
32
26
11
11m
We have thus successfully developed a mild and efficient
protocol for the convenient synthesis of tetrahydrobenz[5,6]-
azepino[2,1-a]isoquinolines from stabilized azomethine
ylides. The mechanistic course of the reaction suggests the
involvment of an 8p-electrocyclization process, followed
by a sigmatropic 1,5-hydrogen shift. This methodology
may find application in the synthesis of the pharmacologi-
cally interesting homoprotoberberine derivatives.14
3.1.2. N-[2-(30,40-Diethoxyphenyl)ethyl]-3,3-diphenyl-2-
propenamide (6b). Compound 6b was prepared, in a manner
analogous to that for 6a, from amine 5b (8.4 g, 40 mmol)
and was isolated as a white powder (11.2 g, 67.5%), mp
158–159 ꢀC; [Found: C, 77.9; H, 6.8; N, 3.5. C27H29NO3 re-
quires C, 78.0; H, 7.0; N, 3.4%]; 1H NMR (250 MHz,
CDCl3): 7.35–7.18 (m, 10H, Ar–H), 6.74 (d, 1H,
J¼8.1 Hz, H-50), 6.58 (d, 1H, J¼1.7 Hz, H-20), 6.45 (dd,
1H, J¼8.1 and 1.7 Hz, H-60), 6.35 (s, 1H, H-2), 5.40 (br s,
1H, NH), 4.08–3.98 (m, 4H, OCH2), 3.33 (t, 2H,
J¼7.2 Hz, CH2), 2.48 (t, 2H, J¼7.2 Hz, NCH2), 1.42 (t,
6H, J¼7.0 Hz, 2ꢁCH3); 13C NMR (63 MHz, CDCl3):
166.2 (quat.), 149.4 (quat.), 148.5 (quat.), 147.0 (quat.),
140.6 (quat.), 138.2 (quat.), 132.2 (quat.), 131.1 (CH),
129.1 (2ꢁCH), 128.6 (CH), 128.3 (2ꢁCH), 128.1
(2ꢁCH), 127.7 (2ꢁCH), 122.3 (CH), 120.5 (CH), 113.7
(CH), 113.4 (CH), 64.4 (CH2), 64.2 (CH2), 40.3 (CH2),
34.5 (CH2), 14.7 (2ꢁCH3); IR (KBr, cmꢂ1): 3281, 3107,
3. Experimental
3.1. General
Melting points were determined on a Gallenkamp apparatus
and are uncorrected. Column chromatography was per-
formed using Merck Kieselgel 60, 70–230 mesh, TLC on
aluminium sheets coated with Kieselgel 60 F254. Plates were
stained with anisaldehyde solution (100 ml glacial acetic
acid, 2 ml concd sulfuric acid and 1 ml anisaldehyde) and
heated at ca. 150 ꢀC. IR spectra were obtained on a Bruker
VECTOR 22 FTIR instrument. NMR spectra were obtained
on Varian INOVA 500, Bruker DRX-500 and Bruker 250
instruments. Chemical shifts are given relative to dTMS. All
solvents were purified according to standard procedures.

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J. Toth et al. / Tetrahedron 62 (2006) 5725–5735
5728
2955, 2845, 1638, 1612, 1539, 1520, 1441, 1386, 1301,
1282, 1271, 1150, 1132, 1022.
CH]), 7.00 (s, 1H, H-5), 6.91 (s, 1H, H-8), 5.58 (d, 1H,
J¼17.4 Hz, NCH2), 5.17 (d, 1H, J¼17.4 Hz, NCH2), 3.79
(s, 3H, OCH3), 3.69 (s, 3H, OCH3), 3.60 (s, 3H, OCH3),
3.55 (m, 2H, H-4), 3.26 (m, 2H, H-3); 13C NMR (63 MHz,
DMSO-d6): 172.1 (quat.), 166.6 (quat.), 158.2 (quat.),
155.7 (quat.), 147.0 (quat.), 139.2 (quat.), 137.6 (quat.),
134.5 (quat.), 130.4 (CH), 130.0 (2ꢁCH), 129.9 (CH),
129.4 (2ꢁCH), 128.7 (2ꢁCH), 128.3 (2ꢁCH), 117.6
(quat.), 117.1 (CH), 114.5 (CH), 110.9 (CH), 57.6 (CH2),
56.5 (CH3), 55.5 (CH3), 53.1 (CH3), 50.8 (CH2), 27.0
(CH2); IR (KBr, cmꢂ1): 3001, 2950, 2922, 2861, 2832,
1747, 1606, 1550, 1520, 1464, 1387, 1338, 1294, 1270,
1218, 1014.
3.1.3. 6,7-Dimethoxy-1-(20,20-diphenyl-10-ethenyl)-3,4-
dihydroisoquinoline (7a). N-[2-(3,4-Dimethoxyphenyl)-
ethyl]-3,3-diphenyl-2-propenamide 6a (7.0 g, 18 mmol) was
dissolved in dry benzene (30 ml) and freshly distilled phos-
phorus oxychloride (3.67 g, 24 mmol) was added dropwise
to the well-stirred mixture at 0 ꢀC. The reaction mixture
was then refluxed and stirred for 4 h, followed by cooling
to room temperature. Then benzene was decanted and the
semi-solid residue was stirred overnight with an excess of
10% aqueous sodium hydroxide solution. The aqueous phase
was extracted with ethyl acetate (3ꢁ25 ml) and the com-
bined organic extracts were washed with brine (25 ml),
then dried (MgSO4) and the solvent evaporated in vacuo to
yield the title product as a yellow solid (4.92 g, 74%), mp
3.1.6. 6,7-Diethoxy-1-(20,20-diphenyl-10-ethenyl)-2-
methoxycarbonylmethyl-3,4-dihydroisoquinolinium
bromide (8b). Compound 8b was prepared analogously to
8a from 7b (0.5 g, 1.25 mmol) and was isolated as a yellow
powder (0.68 g, 100%), mp 266–267 ꢀC; [Found: C, 65.9;
H, 5.7; N, 2.7. C30H32NO4Br requires C, 65.6; H, 5.9; N,
1
171 ꢀC (lit.10a 168–170 ꢀC); H NMR (250 MHz, DMSO-
d6): 7.40–7.30 (m, 6H, Ar–H), 7.10 (m, 4H, Ar–H), 6.85
(s, 1H, H-8), 6.79 (s, 1H, H-5), 6.57 (s, 1H, CH]), 3.82
(s, 3H, OMe), 3.70 (s, 3H, OMe), 3.59 (t, 2H, J¼7.5 Hz,
H-4), 2.55 (t, 2H, J¼7.5 Hz, H-3); 13C NMR (63 MHz,
DMSO-d6): 164.2 (quat.), 150.1 (quat.), 148.0 (quat.),
146.5 (quat.), 141.7 (quat.), 139.2 (quat.), 130.7 (quat.),
129.5 (2ꢁCH), 128.0 (2ꢁCH), 127.7 (CH), 127.2 (4ꢁCH),
125.5 (2ꢁCH), 121.2 (quat.), 109.6 (CH), 109.4 (CH), 55.5
(CH3), 55.3 (CH3), 46.7 (CH2), 25.0 (CH2); IR (KBr, cmꢂ1):
2995, 2952, 2937, 2904, 2825, 1616, 1595, 1563, 1509,
1490, 1461, 1404, 1361, 1346, 1331, 1317, 1287, 1271,
1232, 1142, 1075, 1026; (HRMS Found: m/z 369.1711.
C25H23NO2 requires m/z 369.1729).
1
2.6%]; H NMR (250 MHz, CDCl3): 7.50–7.43 (m, 5H,
Ar–H), 7.18 (m, 6H, Ph–H and CH]), 6.97 (s, 1H, H-5),
6.72 (s, 1H, H-8), 5.73 (d, 1H, J¼17.9 Hz, NCH2), 5.22 (d,
1H, J¼17.9 Hz, NCH2), 4.34–4.17 (4H, m, 2ꢁOCH2), 3.80
(s, 3H, OCH3), 3.51 (2H, m, H-4), 3.22 (2H, m, H-3), 1.42
(3H, t, J¼6.9 Hz, CH3), 1.27 (3H, t, J¼6.9 Hz, CH3); 13C
NMR (63 MHz, CDCl3): 172.7 (quat.), 166.9 (quat.), 159.3
(quat.), 156.6 (quat.), 147.3 (quat.), 138.9 (quat.), 137.2
(quat.), 130.9 (CH), 130.4 (CH), 130.2 (2ꢁCH), 129.4
(2ꢁCH), 129.0 (2ꢁCH), 128.7 (2ꢁCH), 117.8 (quat.),
116.5 (CH), 115.7 (CH), 111.4 (CH), 65.3 (CH2), 65.0
(CH2), 58.7 (CH2), 53.3 (OCH3), 51.7 (CH2), 26.2 (CH2),
14.7 (CH3), 14.4 (CH3); IR (KBr, cmꢂ1): 3406, 2979, 2934,
1753, 1604, 1550, 1519, 1475, 1444, 1387, 1334, 1292,
1270, 1215, 1180, 1031.
3.1.4. 6,7-Diethoxy-1-(20,20-diphenyl-10-ethenyl)-3,4-di-
hydroisoquinoline (7b). Compound 7b was prepared, in
a manner analogous to that for 7a, from 6b (9.95 g,
24 mmol) and was isolated as a yellow semi-solid material
(6.50 g, 69%); 1H NMR (250 MHz, CDCl3): 7.41–7.12 (m,
11H, Ar–H), 6.85 (s, 1H, H-5), 6.62 (s, 1H, CH]), 4.19
(q, 2H, J¼7.0 Hz, OCH2), 3.81 (m, 4H, H-4 and OCH2),
2.89 (br s, 2H, H-3), 1.45 (t, 3H, J¼7.0 Hz, CH3), 1.28 (t,
3H, J¼7.0 Hz, CH3); 13C NMR (63 MHz, CDCl3): 164.2
(quat.), 150.3 (quat.), 147.7 (quat.), 146.3 (quat.), 142.0
(quat.), 139.4 (quat.), 130.95 (quat.), 129.6 (2ꢁCH), 128.1
(2ꢁCH), 127.9 (3ꢁCH), 127.8 (CH), 127.3 (2ꢁCH),
125.9 (CH), 121.6 (quat.), 112.3 (CH), 111.2 (CH), 64.6
(CH2), 63.95 (CH2), 47.0 (CH2), 25.2 (CH2), 14.5 (CH3),
14.4 (CH3); IR (KBr, cmꢂ1): 2955, 2947, 2911, 1612,
1599, 1567, 1514, 1488, 1462, 1404, 1388, 1342, 1337,
1319, 1277, 1233, 1200, 1144, 1075, 1033; (HRMS Found:
m/z 397.2055. C27H27NO2 requires m/z 397.2041).
3.1.7. 2-Benzyl-6,7-dimethoxy-1-(20,20-diphenyl-10-
ethenyl)-3,4-dihydroisoquinolinium bromide (8c). Com-
pound 8c was prepared analogously to 8a from 7a (0.5 g,
1.35 mmol), benzyl bromide (0.36 ml, 0.50 g, 3 mmol) and
was isolated as a yellow powder (0.72 g, 98%), mp 241–
242 ꢀC; [Found: C, 71.2; H, 5.7; N, 2.7. C32H30NO2Br
1
requires C, 71.2; H, 5.6; N, 2.6%]; H NMR (250 MHz,
DMSO-d6): 7.52–7.31 (m, 11H, Ph–H), 7.20 (m, 4H, Ph–H),
7.08 (s, 1H, CH]), 7.00 (s, 1H, H-5), 6.92 (s, 1H, H-8),
5.53 (br s, 2H, NCH2), 3.78 (s, 3H, OMe), 3.70 (m, 2H,
H-4), 3.63 (s, 3H, OMe), 3.02 (m, 2H, H-3); 13C NMR
(63 MHz, DMSO-d6): 170.7 (quat.), 156.0 (quat.), 155.5
(quat.), 147.0 (quat.), 139.2 (quat.), 137.5 (quat.), 133.8
(quat.), 132.5 (quat.), 130.1 (CH), 129.6 (CH), 129.4
(2ꢁCH), 129.0 (7ꢁCH), 128.75 (2ꢁCH), 128.3 (2ꢁCH),
117.9 (quat.), 117.8 (CH), 114.4 (CH), 110.8 (CH), 59.8
(CH2), 56.3 (CH3), 55.6 (CH3), 49.8 (CH2), 24.9 (CH2); IR
(KBr, cmꢂ1): 2952, 2949, 2934, 2901, 2867, 1606, 1550,
1520, 1455, 1384, 1337, 1291, 1215, 1171, 1001.
3.1.5. 6,7-Dimethoxy-1-(20,20-diphenyl-10-ethenyl)-2-meth-
oxycarbonylmethyl-3,4-dihydroisoquinolinium bromide
(8a). Compound 8a 6,7-dimethoxy-1-(20,20-diphenyl-10-
ethenyl)-3,4-dihydroisoquinoline (0.5 g, 1.35 mmol) was
dissolved in dry diethyl ether (30 ml) and methyl bromoace-
tate (0.56 ml, 0.82 g, 6 mmol) was added. The reaction mix-
ture was stirred at room temperature overnight. The yellow
precipitate was filtered off, washed with diethyl ether and
dried in vacuo to give a yellow powder (0.70 g, 100%), mp
260–262 ꢀC; [Found: C, 64.5; H, 5.6; N, 2.7. C28H28NO4Br
3.1.8. 2-Benzyl-6,7-diethoxy-1-(20,20-diphenyl-10-
ethenyl)-3,4-dihydroisoquinolinium bromide (8d). Com-
pound 8d was prepared analogously to 8c from 7b (0.5 g,
1.25 mmol) and was isolated as a yellow powder (0.69 g,
96%), mp 272 ꢀC; [Found: C, 71.9; H, 6.1; N, 2.7.
C34H34NO2Br requires C, 71.9; H, 6.0; N, 2.5%]; 1H NMR
(250 MHz, CDCl3): 7.60 (m, 4H, Ar–H), 7.38 (m, 6H,
1
requires C, 64.5; H, 5.4; N, 2.7%]; H NMR (250 MHz,
DMSO-d6): 7.52 (m, 5H, Ph–H), 7.32 (m, 6H, Ph–H and

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5729
Ar–H), 7.12–7.08 (m, 7H, Ar–H and H-5 and CH]), 6.74 (s,
1H, H-8), 5.75 (d, 1H, J¼15 Hz, NCH2), 5.49 (d, 1H,
J¼15 Hz, NCH2), 4.12 (q, 2H, J¼7 Hz, OCH2), 3.95 (q,
2H, J¼7 Hz, OCH2), 3.50 (m, 2H, H-4), 3.00 (m, 2H, H-
3), 1.42 (t, 3H, J¼7 Hz, CH3), 1.36 (t, 3H, J¼7 Hz, CH3);
13C NMR (63 MHz, DMSO-d6): 170.8 (quat.), 155.6
(quat.), 155.2 (quat.), 146.3 (quat.), 139.2 (quat.), 139.1
(quat.), 137.4 (quat.), 133.8 (quat.), 132.4 (CH), 130.0
(CH), 129.5 (CH), 129.4 (2ꢁCH), 128.9 (6ꢁCH), 128.7
(2ꢁCH), 128.3 (2ꢁCH), 118.0 (CH), 117.9 (CH), 116.0
(quat.), 111.5 (CH), 64.6 (CH2), 64.1 (CH2), 59.7 (CH2),
49.7 (CH2), 24.9 (CH2), 14.5 (CH3), 14.3 (CH3); IR (KBr,
cmꢂ1): 2954, 2945, 2933, 2869, 1603, 1551, 1522, 1458,
1384, 1292, 1225, 1141, 1011.
3.1.11. 6,7-Dimethoxy-1-(20,20-diphenyl-10-ethenyl)-2-(2-
oxo-2-phenylethyl)-3,4-dihydroisoquinolinium bromide
(8g). Compound 8g was prepared analogously to 8a
from 7a (0.5 g, 1.35 mmol) and phenacyl bromide (0.60 g,
3 mmol) and was isolated as a yellow powder (0.77 g,
100%), mp 263–264 ꢀC; [Found: C, 70.1; H, 5.2; N, 2.7.
C33H30NO3Br requires C, 69.8; H, 5.3; N, 2.5%]; 1H NMR
(500 MHz, CDCl3): 7.98 (d, 2H, J¼7.4 Hz, Ph–H), 7.89 (d,
2H, J¼7.5 Hz, Ph–H), 7.40 (m, 4H, Ph–H), 7.23 (m, 3H,
Ph–H), 7.18 (s, 1H, H-8), 7.01 (d, 2H, J¼7.4 Hz, Ph–H),
7.00 (s, 1H, H-5), 6.90 (s, 1H, CH]), 6.89 (d, 2H,
J¼7.5 Hz, Ph–H), 5.80 (m, 1H, H-4), 4.66 (d, 1H,
J¼18.4 Hz, NCH2), 4.04 (s, 3H, OMe), 3.98 (s, 3H, OMe),
3.80 (d, 1H, J¼18.4 Hz, NCH2), 3.73 (m, 1H, H-4), 3.47
(m, 1H, H-3), 3.20 (m, 1H, H-3); 13C NMR (125 MHz,
CDCl3): 193.1 (quat.), 177.9 (quat.), 157.2 (quat.), 148.1
(quat.), 144.0 (quat.), 136.8 (quat.), 135.2 (quat.), 134.6
(quat.), 133.2 (quat.), 128.4 (2ꢁCH), 128.3 (5ꢁCH), 127.6
(2ꢁCH), 127.3 (2ꢁCH), 127.1 (CH), 126.9 (CH), 126.6
(2ꢁCH), 121.9 (CH), 120.0 (quat.), 114.3 (CH), 112.9
(CH), 110.8 (CH), 56.2 (CH3), 56.1 (CH3), 44.4 (CH2),
44.1 (CH2), 25.1 (CH2); IR (KBr, cmꢂ1): 3422, 3011, 2950,
1684, 1625, 1603, 1559, 1527, 1448, 1426, 1402, 1343,
1299, 1169, 1011.
3.1.9. 2-Allyl-6,7-dimethoxy-1-(20,20-diphenyl-10-ethenyl)-
3,4-dihydroisoquinolinium bromide (8e). 6,7-Dimethoxy-
1-(20,20-diphenyl-10-ethenyl]-3,4-dihydroisoquinoline (0.5 g,
1.35 mmol) was dissolved in allyl bromide (8 ml). The result-
ing solution was heated for 24 h under reflux, under an argon
atmosphere. The excess allyl bromide was removed in vacuo
and the residue was triturated with dry diethyl ether. The
yellow precipitate was filtered off, washed with diethyl ether
and dried in vacuo. The product is a yellow powder (0.63 g,
95%), mp 233–234 ꢀC; [Found: C, 68.8; H, 6.1; N, 2.7.
3.1.12. 6,7-Diethoxy-1-(20,20-diphenyl-10-ethenyl)-2-(2-
oxo-2-phenylethyl)-3,4-dihydroisoquinoliniumbromide
(8h). Compound 8h was prepared analogously to 8a from 7b
phenacyl bromide (0.60 g, 3 mmol) and was isolated as a yel-
low powder (0.75 g, 100%); mp 260–261 ꢀC; [Found: C,
70.5; H, 6.1; N, 2.3. C35H34NO3Br requires C, 70.6; H, 5.8;
1
C28H28NO2Br requires C, 68.7; H, 5.8; N, 2.9%]; H NMR
(250 MHz, DMSO-d6): 7.46–7.25 (m, 10H, Ar–H), 7.17 (s,
2H, H-5 and H-8), 7.15 (s, 1H, CH]), 5.99 (d, 1H,
J¼8.1 Hz, allyl–H), 5.80 (m, 1H, allyl–H), 5.45 (m, 1H,
allyl–H), 4.76 (d, 1H, J¼18.8 Hz, NCH2), 4.39 (d, 1H,
J¼18.8 Hz, NCH2), 3.93 (s, 3H, OMe), 3.90 (s, 3H, OMe),
3.62 (m, 2H, H-4), 3.21 (m, 2H, H-3); 13C NMR (63 MHz,
DMSO-d6): 175.6 (quat.), 157.0 (quat.), 148.2 (quat.), 144.8
(quat.), 141.2 (quat.), 139.2 (quat.), 133.5 (quat.), 130.2
(CH), 128.8 (CH), 128.5 (2ꢁCH), 128.3 (3ꢁCH), 127.1
(2ꢁCH), 126.7 (2ꢁCH), 124.6 (CH2), 114.9 (quat.), 115.8
(CH), 113.5 (CH), 111.7 (CH), 56.6 (CH3), 56.4 (CH3), 44.5
(CH2), 43.2 (CH2), 25.2 (CH2); IR (KBr, cmꢂ1): 3005,
2952, 2934, 2867, 1627, 1602, 1559, 1526, 1466, 1423,
1398, 1342, 1298, 1278, 1218, 1167, 1006.
1
N, 2.3%]; H NMR (500 MHz, CDCl3): 8.07 (m, 1H, Ph–
H), 7.98 (d, 2H, J¼7.8 Hz, Ph–H), 7.86 (d, 2H, J¼8.1 Hz,
Ph–H), 7.40 (m, 3H, Ph–H), 7.24 (m, 3H, Ph–H and H-8),
7.14 (m, 2H, Ph–H), 7.00 (m, 2H, Ph–H and H-5), 6.92 (s,
1H, CH]), 6.90 (m, 2H, Ph–H), 5.77 (m, 1H, H-4), 4.63
(d, 1H, J¼17.1 Hz, NCH2), 4.25 (q, 2H, J¼7.0 Hz, OCH2),
4.15 (q, 2H, J¼7.0 Hz, OCH2), 3.72 (d, 1H, J¼17.1 Hz,
NCH2), 3.70 (m, 1H, H-4), 3.49 (m, 1H, H-4), 3.17 (m, 2H,
H-3), 1.51 (t, 3H, J¼7.0 Hz, CH3), 1.49 (t, 3H, J¼7.0 Hz,
CH3); 13C NMR (125 MHz, CDCl3): 194.5 (quat.), 177.1
(quat.), 158.0 (quat.), 148.3 (quat.), 144.2 (quat.), 137.3
(quat.), 135.7 (quat.), 134.4 (quat.), 133.8 (quat.), 129.6
(2ꢁCH), 129.3 (2ꢁCH), 128.7 (2ꢁCH), 128.3 (2ꢁCH),
128.0 (2ꢁCH), 127.8 (CH), 127.6 (3ꢁCH), 127.5 (CH),
114.7 (CH), 114.0 (quat.), 112.1 (CH), 112.0 (CH), 65.5
(2ꢁCH2), 45.7 (CH2), 44.7 (CH2), 26.2 (CH2), 14.6 (CH3),
14.3 (CH3); IR (KBr, cmꢂ1): 3031, 2969, 2943, 1670,
1629, 1599, 1587, 1557, 1527, 1464, 1456, 1446, 1426,
1399, 1340, 1298, 1228, 1169, 1093, 1010.
3.1.10. 2-Allyl-6,7-diethoxy-1-(20,20-diphenyl-10-ethenyl)-
3,4-dihydroisoquinolinium bromide (8f). Compound 8f
was prepared analogously to 8e from 7b (0.5 g, 1.25 mmol)
and was isolated as a yellow powder (0.62 g, 97%), mp
274–278 ꢀC; [Found: C, 69.6; H, 6.2; N, 2.7. C30H32NO2Br
1
requires C, 69.6; H, 6.2; N, 2.7%]; H NMR (250 MHz,
CDCl3): 7.47 (m, 6H, Ar–H), 7.26 (m, 4H, Ar–H), 7.02 (s,
1H, CH]), 6.98 (s, 1H, H-5), 6.73 (s, 1H, H-8), 5.73 (m,
1H, allyl–H), 5.45 (m, 2H, allyl–H), 5.13 (d, 1H, J¼19 Hz,
NCH2), 4.90 (d, 1H, J¼19 Hz, NCH2), 4.35–4.15 (m, 4H,
2ꢁOCH2CH3), 3.54 (m, 2H, H-4), 3.29 (m, 2H, H-3), 1.48
(t, 3H, J¼6.9 Hz, CH3), 1.23 (t, 3H, J¼6.9 Hz, CH3); 13C
NMR (63 MHz, CDCl3): 170.8 (quat.), 157.4 (quat.), 156.3
(quat.), 147.4 (quat.), 138.9 (quat.), 137.3 (quat.), 134.2
(quat.), 130.6 (CH), 130.2 (CH), 129.8 (2ꢁCH), 129.2
(2ꢁCH), 128.9 (2ꢁCH), 128.8 (2ꢁCH), 128.3 (CH), 122.6
(CH2), 118.1 (quat.), 116.4 (CH), 116.1 (CH), 111.6 (CH),
65.3 (CH2), 65.1 (CH2), 60.1 (CH2), 49.0 (CH2), 26.1
(CH2), 14.7 (CH3), 14.4 (CH3); IR (KBr, cmꢂ1): 2966,
2944, 2934, 2868, 1628, 1603, 1561, 1522, 1454, 1399,
1345, 1278, 1222, 1169, 1122, 1008.
3.1.13. 6,7-Dimethoxy-1-(20,20-diphenyl-10-ethenyl)-2-[2-
(4-methoxyphenyl)-2-oxoethyl]-3,4-dihydroisoquinoli-
nium bromide (8i). Compound 8i was prepared analogously
to 8a from 7a (0.5 g, 1.35 mmol) and 20-bromo-4-methoxy-
acetophenone (0.69 g, 3 mmol) and was isolated as a yellow
powder (0.77 g, 100%), mp 272 ꢀC; [Found: C, 68.3; H, 5.2;
N, 2.3. C34H34NO4Br requires C, 68.2; H, 5.4; N, 2.3%]; 1H
NMR (500 MHz, CDCl3): 7.88 (d, 2H, J¼8.3 Hz, Ar–20 and
60H), 7.41 (m, 4H, Ph–H), 7.30 (m, 6H, Ph–H), 7.06 (s, 1H,
H-8), 6.94 (s, 1H, H-5 and CH]), 6.58 (d, 2H, J¼8.3 Hz,
Ar–30 and 50H), 5.63 (m, 1H, H-4), 4.81 (d, 1H,
J¼19.0 Hz, NCH2), 4.68 (d, 1H, J¼19.0 Hz, NCH2), 4.03

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(s, 3H, OMe), 3.98 (s, 3H, OMe), 3.77 (s, 3H, OMe), 3.70
(m, 1H, H-4), 3.55 (m, 1H, H-3), 3.22 (m, 1H, H-3); 13C
NMR (125 MHz, CDCl3): 191.8 (quat.), 177.3 (quat.),
164.3 (quat.), 157.7 (quat.), 148.8 (quat.), 144.4 (quat.),
137.6 (quat.), 135.9 (quat.), 134.3 (quat.), 129.2 (2ꢁCH),
128.8 (2ꢁCH), 128.7 (2ꢁCH), 128.6 (quat.), 128.5 (CH),
127.9 (2ꢁCH), 127.6 (2ꢁCH), 127.4 (CH), 115.1 (quat.),
114.3 (quat.), 113.6 (2ꢁCH), 112.1 (CH), 111.3 (CH),
56.9 (CH3), 56.7 (CH3), 55.8 (CH3), 45.5 (CH2), 45.1
(CH2), 26.0 (CH2); IR (KBr, cmꢂ1): 2936, 2838, 1675,
1600, 1559, 1526, 1513, 1457, 1424, 1401, 1341, 1297,
1244, 1169, 1045.
(CH), 102.1 (CH), 76.5 (CH, C-14a), 62.1 (CH), 55.8
(CH3), 55.7 (CH3), 51.3 (CH3), 46.5 (CH2), 29.0 (CH2); IR
(KBr, cmꢂ1): 2985, 2956, 2834, 1723, 1513, 1464, 1450,
1355, 1342, 1275, 1234, 1212, 1177, 1149, 1025.
3.2.2. Methyl 2,3-diethoxy-13-phenyl-5,6,8,14a-tetrahy-
drobenz[5,6]azepino[2,1-a]isoquinoline-8-carboxylate
(11b). White powder (0.30 g, 86%), mp 157–159 ꢀC;
[Found: C, 76.7; H, 6.5; N, 2.9. C30H31NO4 requires C,
1
76.7; H, 6.6; N, 3.0%]; H NMR (250 MHz, CDCl3): 7.60
(m, 2H, Ar–H), 7.37 (m, 2H, Ar–H), 7.27–7.11 (m, 7H,
Ar–H), 6.63 (s, 1H, H-14), 5.46 (s, 1H, H-14a), 4.79 (s,
1H, H-8), 4.07 (m, 4H, 2ꢁOCH2), 3.31 (s, 3H, CO2CH3),
3.27 (m, 2H, CH2-6), 2.78 (m, 2H, CH2-5), 1.44 (t, 3H,
J¼7.1 Hz, CH3), 1.42 (t, 3H, J¼7.1 Hz, CH3); 13C NMR
(63 MHz, CDCl3): 170.8 (quat.), 149.3 (quat.), 147.1
(quat.), 146.4 (quat.), 144.7 (quat.), 143.9 (quat.), 128.6
(CH), 128.2 (2ꢁCH), 127.8 (CH), 127.6 (2ꢁCH), 127.5
(CH), 127.1 (quat.), 126.5 (CH), 126.1 (CH), 121.3 (quat.),
119.6 (quat.), 112.3 (CH), 109.7 (CH), 102.0 (CH), 76.6
(CH), 64.6 (CH2), 64.3 (CH2), 62.2 (CH), 51.4 (CH3),
46.6 (CH2), 29.0 (CH2), 14.8 (CH3), 14.7 (CH3); IR (KBr,
cmꢂ1): 3053, 3030, 2980, 2932, 2879, 2815, 1749, 1731,
1608, 1509, 1444, 1392, 1333, 1275, 1235, 1208, 1177,
1153, 1108, 1041.
3.1.14. 2-(2-Cyanobenzyl)-1-(20,20-diphenyl-10-ethenyl)-
6,7-dimethoy-3,4-dihydroisoquinolinium bromide (8j).
Compound 8j was prepared analogously to 8a from 7a
(0.5 g, 1.35 mmol) and 2-bromomethyl-benzonitrile (0.39 g,
2 mmol) and was isolated as a yellow powder (0.76 g, 99%),
mp 192–193 ꢀC; [Found: C, 70.2; H, 5.2; N, 4.8.
C33H29N2O2Br requires C, 70.2; H, 5.2; N, 5.0%]; 1H
NMR (500 MHz, CDCl3): 8.24 (d, 1H, J¼7.8 Hz, Ar–30H),
7.76 (d, 1H, J¼7.8 Hz, Ar–60H), 7.72 (t, 1H, J¼7.8 Hz,
Ar–50H), 7.59–7.44 (m, 5H, Ph–H and Ar–40H), 7.40 (d,
2H, J¼7.5 Hz, Ph–H), 7.35 (m, 2H, Ph–H and H-8), 7.26
(t, 1H, J¼7.5 Hz, Ph–H), 7.19 (d, 2H, J¼7.5 Hz, Ph–H),
7.07 (s, 1H, H-5), 6.79 (s, 1H, CH]), 6.21 (d, 1H, J¼
15.1 Hz, NCH2), 5.72 (d, 1H, J¼15.1 Hz, NCH2), 3.91 (s,
3H, OMe), 3.73 (s, 3H, OMe), 3.55 (m, 1H, H-4), 3.47 (m,
1H, H-4), 2.98 (m, 1H, H-3), 2.78 (m, 1H, H-3); 13C NMR
(125 MHz, CDCl3): 171.9 (quat.), 158.4 (quat.), 156.3
(quat.), 147.5 (quat.), 138.5 (quat.), 136.7 (quat.), 135.0
(quat.), 134.3 (quat.), 134.0 (CH), 133.3 (CH), 133.2 (CH),
130.4 (CH), 130.0 (CH), 129.9 (CH), 129.6 (2ꢁCH), 128.8
(2ꢁCH), 128.65 (2ꢁCH), 128.6 (2ꢁCH), 118.1 (quat.),
117.3 (CH), 116.7 (quat.), 113.9 (CH), 111.6 (CH), 110.3
(CH), 58.0 (CH2), 56.5 (CH3), 55.7 (CH3), 48.8 (CH2),
25.8 (CH2); IR (KBr, cmꢂ1): 2937, 2889, 2224, 1604,
1545, 1521, 1447, 1386, 1338, 1292, 1272, 1216, 1172, 1002.
3.2.3. 2,3-Dimethoxy-8,13-diphenyl-5,6,8,14a-tetra-
hydrobenz[5,6]azepino[2,1-a]isoquinoline (11c). White
powder (0.26 g, 77%), mp 140 ꢀC; [Found: C, 83.7; H, 6.2;
1
N, 3.0. C32H29NO2 requires C, 83.6; H, 6.4; N, 3.0%]; H
NMR (250 MHz, CDCl3): 7.53 (m, 2H, Ar–H), 7.33 (m,
2H, Ar–H), 7.20 (m, 2H, Ar–H), 7.02 (m, 7H, Ar–H), 6.87
(m, 3H, Ar–H), 6.63 (s, 1H, H-14), 5.50 (s, 1H, H-14a),
5.17 (s, 1H, H-8), 3.89 (s, 3H, OCH3), 3.87 (s, 3H, OCH3),
3.08 (m, 1H, CH2-6), 3.02 (m, 1H, CH2-6), 2.70 (m, 2H,
CH2-5); 13C NMR (63 MHz, CDCl3): 147.6 (quat.), 147.4
(quat.), 145.5 (quat.), 143.6 (quat.), 138.4 (quat.), 129.9
(2ꢁCH), 129.2 (quat.), 129.1 (CH), 128.1 (2ꢁCH), 127.9
(3ꢁCH), 127.7 (quat.), 127.4 (quat.), 127.0 (CH), 126.9
(3ꢁCH), 125.7 (2ꢁCH), 120.1 (quat.), 110.7 (CH), 107.2
(CH), 103.2 (CH), 77.8 (CH), 63.2 (CH), 55.9 (2ꢁCH3),
45.6 (CH2), 29.4 (CH2); IR (KBr, cmꢂ1): 2945, 2922, 2830,
1608, 1500, 1462, 1337, 1270, 1231, 1212, 1174, 1148, 1020.
3.2. 1,7-Electrocyclizations—method A
The corresponding 1-(20,20-diphenyl-10-ethenyl)-3,4-di-
hydroisoquinolinium bromide (0.75 mmol) was dissolved
in dry methanol (10 ml) and triethylamine (0.11 ml,
1.5 mmol) was added. The reaction mixture was stirred for
24 h at room temperature under an argon atmosphere. The
precipitated products were filtered off, washed with ethanol
and dried in air.
3.2.4. 2,3-Diethoxy-8,13-diphenyl-5,6,8,14a-tetrahydro-
benz[5,6]azepino[2,1-a]isoquinoline (11d). White powder
(0.30 g, 82%), mp 142–143 ꢀC; [Found: C, 83.8; H, 7.0; N,
1
2.9. C34H33NO2 requires C, 83.7; H, 6.8; N, 2.9%]; H
NMR (250 MHz, CDCl3): 7.58 (m, 2H, Ar–H), 7.37 (m,
2H, Ar–H), 7.27 (m, 2H, Ar–H), 7.12–7.01 (m, 10H, Ar–
H), 6.69 (s, 1H, H-14), 5.52 (s, 1H, H-14a), 5.22 (s, 1H, H-
8), 4.13 (m, 4H, OCH2), 3.17 (m, 1H, CH2-6), 2.96 (m, 1H,
CH2-6), 2.74 (m, 2H, CH2-5), 1.51 (t, 3H, J¼7.1 Hz, CH3),
1.49 (t, 3H, J¼7.1 Hz, CH3); 13C NMR (63 MHz, CDCl3):
149.0 (quat.), 147.2 (quat.), 145.0 (quat.), 144.4 (quat.),
143.5 (quat.), 129.8 (2ꢁCH), 129.0 (2ꢁCH), 127.9
(2ꢁCH), 127.75 (2ꢁCH), 127.7 (quat.), 127.6 (quat.),
127.4 (quat.), 127.2 (2ꢁCH), 126.8 (CH), 125.5 (3ꢁCH),
119.9 (quat.), 112.3 (CH), 109.4 (CH), 102.8 (CH), 77.7
(CH, C-8), 64.5 (CH2), 64.2 (CH2), 63.0 (CH), 45.4 (CH2),
29.2 (CH2), 14.6 (CH3), 14.5 (CH3); IR (KBr, cmꢂ1): 2963,
2955, 2932, 2811, 1609, 1508, 1488, 1463, 1338, 1270,
1233, 1210, 1179, 1166, 1141, 1011.
3.2.1. Methyl 2,3-dimethoxy-13-phenyl-5,6,8,14a-tetra-
hydrobenz[5,6]azepino[2,1-a]isoquinoline-8-carboxylate
(11a). White powder (0.27 g, 83%), mp 148–149 ꢀC;
[Found: C, 76.0; H, 6.2; N, 2.9. C28H27NO4 requires C,
1
76.2; H, 6.2; N, 3.1%]; H NMR (250 MHz, CDCl3): 7.63
(m, 2H, Ar–H), 7.40 (m, 2H, Ar–H), 7.26 (m, 6H, Ar–H),
7.11 (s, 1H, H-1), 6.64 (s, 1H, H-14), 5.52 (s, 1H, H-14a),
4.82 (s, 1H, H-8), 3.89 (s, 6H, 2ꢁOCH3), 3.34 (s, 3H,
CO2CH3), 3.31 (m, 2H, H-6), 2.18 (m, 2H, H-5); 13C NMR
(63 MHz, CDCl3): 170.7 (quat.), 149.3 (quat.), 147.4
(quat.), 146.2 (quat.), 144.5 (quat.), 143.8 (quat.), 128.6
(quat.) 128.5 (CH, C-9), 128.2 (2ꢁCH), 127.9 (CH, C-11),
127.8 (CH), 127.5 (2ꢁCH), 126.5 (CH, C-10), 126.0 (CH,
C-12), 121.1 (quat.), 119.5 (quat.), 110.4 (CH), 107.2

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3.2.5. 8-Ethenyl-2,3-dimethoxy-13-phenyl-5,6,8,14a-tet-
rahydrobenz[5,6]azepino[2,1-a]isoquinoline (11e). White
powder (0.16 g, 53%), mp 133 ꢀC; [Found: C, 82.4; H, 6.5;
powder (0.31 g, 80%); mp 167 ꢀC; [Found: C, 81.5; H,
6.4; N, 2.7. C30H31NO2 requires C, 81.5; H, 6.4; N, 2.7%];
1H NMR (250 MHz, CDCl3): 7.95 (d, 2H, J¼7.7 Hz, Ar–
20 and 60H), 7.63 (d, 2H, J¼7.4 Hz, Ph–20 and 60H), 7.37–
7.21 (m, 3H), 7.17–6.99 (m, 6H), 6.66 (m, 3H), 6.64 (s,
1H, H-14), 5.51 (s, 1H, H-14a), 5.35 (s, 1H, H-8), 4.24–
4.07 (m, 4H, OCH2), 3.12 (m, 1H, CH2-6), 3.01 (m, 1H,
CH2-6), 2.84 (m, 1H, CH2-5), 2.73 (m, 1H, CH2-5), 1.50
(t, 3H, J¼7.1 Hz, CH3), 1.47 (t, 3H, J¼7.1 Hz, CH3); 13C
NMR (63 MHz, CDCl3): 200.0 (quat.), 149.1 (quat.),
148.0 (quat.), 147.0 (quat.), 144.1 (quat.), 144.0 (quat.),
129.9 (CH), 128.9 (CH), 128.6 (2ꢁCH), 128.5 (CH),
127.9 (2ꢁCH), 127.7 (CH), 127.3 (2ꢁCH), 127.2 (quat.),
127.1 (2ꢁCH), 127.0 (CH), 126.1 (CH), 125.9 (quat.),
125.5 (quat.), 119.4 (quat.), 111.8 (CH), 109.5 (CH), 101.6
(CH), 80.5 (CH), 64.5 (CH2), 64.1 (CH2), 62.5 (CH), 46.1
(CH2), 28.8 (CH2), 14.5 (CH3), 14.4 (CH3); IR (KBr, cmꢂ1):
2957, 2954, 2899, 2834, 1691, 1626, 1606, 1562, 1524,
1444, 1400, 1279, 1233, 1144, 1102, 1024, 1011.
1
N, 3.0. C28H27NO2 requires C, 82.1; H, 6.6; N, 3.4%]; H
NMR (250 MHz, CDCl3): 7.44 (m, 2H, Ar–H), 7.33 (m,
2H, Ar–H), 7.25–7.11 (m, 7H, Ar–H), 6.64 (s, 1H, H-14),
5.67 (s, 1H, H-14a), 5.46–5.33 (m, 3H, vinyl–H and H-8),
5.23 (dd, 1H, J¼2.8 and 8.6 Hz, vinyl–H), 3.88 (s, 3H,
OCH3), 3.87 (s, 3H, OCH3), 3.20 (m, 1H, CH2-6), 3.05
(m, 1H, CH2-6), 2.71 (m, 2H, CH2-5); 13C NMR (63 MHz,
CDCl3): 149.3 (quat.), 149.2 (quat.), 145.9 (quat.), 144.6
(quat.), 136.5 (quat.), 129.7 (quat.), 129.2 (2ꢁCH), 128.3
(CH), 128.2 (CH), 128.0 (quat.), 127.6 (CH), 127.5 (CH),
127.45 (CH), 126.2 (2ꢁCH), 126.1 (CH2), 126.0 (CH),
119.9 (quat.), 112.5 (CH), 109.8 (CH), 103.7 (CH), 78.5
(CH), 60.9 (CH), 55.95 (CH3), 55.9 (CH3), 45.2 (CH2),
29.4 (CH2); IR (KBr, cmꢂ1): 3052, 3011, 2980, 2921,
2811, 1611, 1514, 1478, 1437, 1417, 1389, 1333, 1234,
1184, 1177, 1155, 1111, 1021.
3.2.6. 2,3-Diethoxy-13-phenyl-8-vinyl-5,6,8,14a-tetrahy-
drobenz[5,6]azepino[2,1-a]isoquinoline (11f). White pow-
der (0.16 g, 50%), mp 139–140 ꢀC; [Found: C, 82.3; H, 6.9;
3.2.9. 2,3-Dimethoxy-13-phenyl-8-(40-methoxybenzoyl)-
5,6,8,14a-tetrahydrobenz[5,6]azepino[2,1-a]isoquinoline
(11i). White powder (0.33 g, 85%), mp 179–180 ꢀC; [Found:
C, 78.9; H, 6.0; N, 2.9. C34H31NO4 requires C, 78.9; H, 6.0;
N, 2.7%]; 1H NMR (500 MHz, CDCl3): 7.85 (d, 2H,
J¼7.5 Hz, Ar–20 and 60H), 7.67 (d, 2H, J¼6.7 Hz, Ph–20
and 60H), 7.35 (m, 2H, H-10 and H-12), 7.17 (m, 4H, Ph–
30, 40 and 50H, H-9), 6.96–6.88 (m, 3H, H-1, H-4 and H-8),
6.63 (s, 1H, H-14), 6.57 (d, 2H, J¼7.5 Hz, Ar–30 and 50H),
5.55 (s, 1H, H-14a), 5.29 (s, 1H, H-8), 3.91 (s, 3H, OMe),
3.88 (s, 3H, OMe), 3.74 (s, 3H, OMe), 3.04 (m, 2H,
CH2-6), 2.81 (m, 1H, CH2-5), 2.70 (m, 1H, CH2-5); 13C
NMR (125 MHz, CDCl3): 198.4 (quat.), 162.7 (quat.),
149.5 (quat.), 147.7 (quat.), 147.3 (quat.), 144.3 (quat.),
144.0 (quat.), 131.5 (2ꢁCH), 130.2 (quat.), 129.5 (2ꢁCH),
128.2 (CH), 127.7 (CH), 127.4 (2ꢁCH), 127.2 (quat.),
126.4 (CH), 125.9 (quat.), 125.85 (CH), 125.8 (CH), 119.8
(quat.), 112.4 (2ꢁCH), 110.7 (CH), 107.5 (CH), 102.3
(CH), 81.2 (CH), 62.8 (CH), 55.9 (CH3), 55.8 (CH3), 55.1
(CH3), 46.5 (CH2), 29.1 (CH2); IR (KBr, cmꢂ1): 3057,
3005, 2965, 2838, 1648, 1593, 1510, 1490, 1457, 1447,
1314, 1300, 1276, 1260, 1235, 1210, 1170, 1020.
1
N, 3.0. C30H31NO2 requires C, 82.3; H, 7.1; N, 3.2%]; H
NMR (250 MHz, CDCl3): 7.44 (m, 2H, Ar–H), 7.33 (m,
2H, Ar–H), 7.25–7.11 (m, 7H, Ar–H), 6.64 (s, 1H, H-14),
5.67 (s, 1H, H-14a), 5.46–5.33 (m, 3H, vinyl and H-8),
5.23 (dd, 1H, J¼2.8 and 8.6 Hz, vinyl–H), 4.09 (m, 4H,
OCH2), 3.18 (m, 1H, CH2-6), 3.08 (m, 1H, CH2-6), 2.76–
2.55 (m, 2H, CH2-5), 1.45 (t, 6H, J¼6.9 Hz, 2ꢁCH3); 13C
NMR (63 MHz, CDCl3): 149.3 (quat.), 149.2 (quat.),
145.8 (quat.), 144.6 (quat.), 136.8 (quat.), 129.7 (quat.),
129.2 (2ꢁCH), 128.3 (CH), 128.1 (CH), 128.0 (quat.),
127.6 (2ꢁCH), 127.5 (CH), 126.2 (2ꢁCH), 126.15 (CH2),
126.1 (CH), 120.0 (quat.), 112.5 (CH), 109.6 (CH), 103.4
(CH, C-1), 78.3 (CH, C-8), 64.8 (OCH2), 64.4 (OCH2),
61.1 (CH), 45.1 (CH2-6), 29.4 (CH2-5), 14.9 (CH3), 14.8
(CH3); IR (KBr, cmꢂ1): 3077, 2978, 2917, 2879, 2807,
1608, 1511, 1474, 1438, 1416, 1388, 1334, 1273, 1233,
1208, 1184, 1150, 1110, 1088, 1037.
3.2.7. 2,3-Dimethoxy-13-phenyl-8-benzoyl-5,6,8,14a-tet-
rahydrobenz[5,6]azepino[2,1-a]isoquinoline (11g). White
powder (0.31 g, 81%), mp 164–165 ꢀC; [Found: C, 81.3; H,
6.0; N, 3.0. C33H29NO3 requires C, 81.3; H, 6.0; N, 2.9%];
1H NMR (250 MHz, CDCl3): 7.98 (d, 2H, J¼7.7 Hz, Ph–
20 and 60H), 7.65 (d, 2H, J¼7.4 Hz, Ph–20 and 60H), 7.37–
7.24 (m, 3H), 7.15–6.70 (m, 9H), 6.67 (s, 1H, H-14), 5.50
(s, 1H, H-14a), 5.32 (s, 1H, H-8), 4.01 (s, 3H, OMe), 3.90
(s, 3H, OMe), 3.15 (m, 1H, CH2-6), 3.05 (m, 1H, CH2-6),
2.72 (m, 2H, CH2-5); 13C NMR (63 MHz, CDCl3): 199.8
(quat.), 148.6 (quat.), 148.3 (quat.), 147.4 (quat.), 144.1
(quat.), 139.9 (quat.), 132.0 (quat.), 130.0 (quat.), 128.8
(CH), 128.6 (2ꢁCH), 128.4 (CH), 128.0 (2ꢁCH), 127.8
(CH), 127.3 (2ꢁCH), 127.2 (CH), 127.1 (2ꢁCH), 126.9
(CH), 126.3 (CH), 125.4 (quat.), 119.3 (quat.), 111.9 (CH),
109.3 (CH), 101.6 (CH), 80.5 (CH), 56.3 (CH3), 56.2
(CH3), 62.5 (CH), 46.1 (CH2), 28.8 (CH2); IR (KBr, cmꢂ1):
2967, 2954, 2887, 1692, 1625, 1606, 1560, 1525, 1448,
1428, 1404, 1349, 1278, 1230, 1170, 1024, 1001.
3.2.10. 2,3-Dimethoxy-8-(2-cyanophenyl)-13-phenyl-
5,6,8,14a-tetrahydrobenz[5,6]azepino[2,1-a]isoquinoline
(11j). White powder (0.26 g, 73%), mp 155 ꢀC; [Found: C,
82.0; H, 5.9; N, 5.7. C33H28N2O2 requires C, 81.8; H, 5.8;
N, 5.8%]; 1H NMR (500 MHz, CDCl3): 7.57 (d, 2H,
J¼7.5 Hz, Ph–20 and 60H), 7.48 (dd, 1H, J¼2.1 and
7.2 Hz, Ar–60H), 7.37 (t, 1H, J¼7.5 Hz, Ph–40H), 7.35 (d,
2H, J¼7.5 Hz, Ph–30 and 50H), 7.23 (d, 1H, J¼7.2 Hz, Ar–
30H), 7.19 (m, 2H, H-10 and H-11), 7.13 (dt, 1H, J¼2.1
and 7.2 Hz, Ar–50H), 7.03 (m, 4H, H-1, H-4, H-12 and
Ar–40H), 6.98 (d, 1H, J¼7.8 Hz, H-9), 6.67 (s, 1H, H-14),
5.80 (s, 1H, H-14a), 5.47 (s, 1H, H-8), 3.93 (s, 3H, OMe),
3.90 (s, 3H, OMe), 2.94 (m, 2H, CH2-6), 2.88 (m, 2H,
CH2-5); 13C NMR (125 MHz, CDCl3): 149.4 (quat.),
147.6 (quat.), 147.0 (quat.), 144.0 (quat.), 143.2 (quat.),
142.9 (quat.), 132.1 (CH), 131.4 (CH), 130.3 (CH), 129.9
(CH), 128.1 (CH), 128.0 (2ꢁCH), 127.5 (2ꢁCH), 127.4
(quat.), 127.1 (2ꢁCH), 126.0 (CH), 125.9 (CH), 125.8
(quat.), 119.8 (quat.), 118.3 (quat.), 112.9 (quat.), 110.6
(CH), 107.3 (CH), 101.3 (CH), 75.0 (CH), 64.3 (CH), 55.8
3.2.8. 2,3-Diethoxy-13-phenyl-8-benzoyl-5,6,8,14a-tetra-
hydrobenz[5,6]azepino[2,1-a]isoquinoline (11h). White

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J. Toth et al. / Tetrahedron 62 (2006) 5725–5735
5732
(CH3), 55.7 (CH3), 44.6 (CH2), 29.4 (CH2); IR (KBr, cmꢂ1):
3058, 2934, 2223, 1700, 1603, 1493, 1450, 1432, 1338,
1275, 1167, 1090, 1002.
ethyl acetate (3ꢁ30 ml) and the combined organic extracts
were washed with brine (30 ml), then dried (MgSO4) and
evaporated in vacuo to give the title product as a yellow solid
(5.34 g, 70%), mp 118–119 ꢀC; [Found: C, 82.0; H, 5.9; N,
4.0. C25H21NO2 requires C, 81.7; H, 5.8; N, 3.8%]; 1H NMR
(500 MHz, CDCl3): 7.78 (d, 1H, J¼7.4 Hz, Flu–H), 7.67 (d,
1H, J¼7.4 Hz, Flu–H), 7.64 (d, 1H, J¼7.4 Hz, Flu–H), 7.55
(d, 1H, J¼7.4 Hz, Flu–H), 7.38 (t, 1H, J¼7.4 Hz, Flu–H),
7.32 (s, 1H, H-8), 7.31 (t, 1H, J¼7.4 Hz, Flu–H), 7.28 (t,
1H, J¼7.4 Hz, Flu–H), 7.06 (t, 1H, J¼7.4 Hz, Flu–H),
6.96 (s, 1H, H-5), 6.77 (s, 1H, CH]), 3.96 (t, 2H,
J¼7.7 Hz, H-4), 3.92 (s, 3H, OMe), 3.63 (s, 3H, OMe),
2.82 (t, 2H, J¼7.7 Hz, H-3); 13C NMR (125 MHz,
CDCl3): 163.7 (quat.), 151.3 (quat.), 147.6 (quat.), 141.3
(quat.), 140.4 (quat.), 139.8 (quat.), 138.8 (quat.), 136.0
(quat.), 131.0 (quat.), 128.9 (CH), 128.8 (CH), 127.0 (CH),
126 5 (quat.), 126.9 (CH), 125.7 (CH), 122.7 (CH), 121.6
(quat.), 120.6 (CH), 119.5 (CH), 119.4 (CH), 110.4 (CH),
109.9 (CH), 56.1 (CH3), 55.9 (CH3), 47.4 (CH2), 25.5
(CH2); IR (KBr, cmꢂ1): 3426, 3001, 2933, 2830, 1714,
1603, 1562, 1512, 1463, 1450, 1357, 1317, 1277, 1207,
1151, 1140, 1024.
3.2.11. N-1-(30,40-Dimethoxyphenethyl)-2-(9H-9-fluo-
renylidenyl)acetamide (12a). 2-(30,40-Dimethoxyphenyl)-
ethylamine (4.54 g, 25 mmol) was dissolved in dry
dichloromethane (30 ml) and triethylamine (3.6 ml, 2.5 g,
25 mmol) was added at 0 ꢀC. Fluorylidenylcarboxylic acid
chloride (6.02 g, 25 mmol), dissolved in dry dichloro-
methane (50 ml), was added dropwise. The reaction mixture
was stirred at room temperature for 3 h and water was added
(50 ml). The organic layer was washed with brine (25 ml),
then dried (MgSO4) and evaporated in vacuo to yield the title
product as a white solid (8.87 g, 92%), mp 154–155 ꢀC;
[Found: C, 78.0; H, 5.9; N, 3.6. C25H23NO3 requires C,
1
77.9; H, 6.0; N, 3.6%]; H NMR (500 MHz, DMSO-d6):
8.68 (d, 1H, J¼7.6 Hz, Flu–H), 8.58 (t, 1H, J¼5.5 Hz,
NH), 7.83 (m, 2H, Flu–H), 7.77 (d, 1H, J¼7.6 Hz, Flu–H),
7.43 (t, 2H, J¼7.6 Hz, Flu–H), 7.34 (t, 1H, J¼7.6 Hz, Flu–
H), 7.30 (t, 1H, J¼7.6 Hz, Flu–H), 7.08 (s, 1H, CH]),
6.80 (m, 2H, Ar–20 and 50H), 6.78 (dd, 1H, J¼1.8 and
8 Hz, Ar–60H), 3.72 (s, 3H, OMe), 3.71 (s, 3H, OMe), 3.51
(m, 2H, H-1), 2.80 (t, 2H, J¼7.2 Hz, H-2); 13C NMR
(125 MHz, DMSO-d6): 165.5 (quat.), 148.8 (quat.), 147.4
(quat.), 141.3 (quat.), 139.6 (quat.), 138.7 (quat.), 135.1
(quat.), 131.9 (CH), 130.1 (quat.), 129.9 (CH), 128.1 (CH),
127.7 (3ꢁCH), 121.1 (CH), 120.6 (CH), 120.5 (CH), 120.2
(CH), 120.0 (quat.), 112.7 (CH), 112.1 (CH), 55.7 (CH3),
55.5 (CH3), 40.7 (CH2), 34.7 (CH2); IR (KBr, cmꢂ1): 3311,
2935, 2841, 1625, 1605, 1516, 1451, 1443, 1301, 1290,
1262, 1236, 1190, 1157, 1141, 1027.
3.2.14. 6,7-Dimethoxy-1-(1-naphthyl)-3,4-dihydroisoqui-
noline (13b). 1-(30,40-Dimethoxyphenethyl)-1-naphthamide
(10.0 g, 29.8 mmol) was dissolved in dry toluene (50 ml) and
freshly distilled phosphorus oxychloride (9.12 g, 60 mmol)
was added dropwise to the well-stirred mixture at 0 ꢀC.
The reaction mixture was stirred at reflux for 6 h, cooled to
5–10 ꢀC and then the mixture was stirred with an excess of
10% aqueous sodium hydroxide solution. The aqueous phase
was washed with ethyl acetate (3ꢁ30 ml) and the combined
organic extracts were washed with brine (30 ml), then dried
(MgSO4) and evaporated in vacuo to yield the title product
as a yellow solid (7.09 g, 75%), mp 105–107 ꢀC; [Found:
C, 79.2; H, 5.9; N, 4.2. C21H19NO2 requires C, 79.5; H,
3.2.12. 1-(30,40-Dimethoxyphenethyl)-1-naphthamide
(12b). Compound 12b was prepared analogously to 6a
from naphthoic-1-carboxylic acid (9.53 g, 50 mmol) and
was isolated as a white powder (10.2 g, 61%), mp 137–
139 ꢀC; [Found: C, 75.0; H, 6.3; N, 4.1. C21H21NO3 requires
C, 75.2; H, 6.3; N, 4.2%]; 1H NMR (500 MHz, DMSO-d6):
8.56 (t, 1H, J¼5.5 Hz, NH), 8.04 (d, 1H, J¼8.9 Hz, Naph–
40H), 7.98 (t, 1H, J¼8.9 Hz, Naph–60H), 7.95 (d, 1H,
J¼8.9 Hz, Naph–80H), 7.56–7.46 (m, 4H, Naph–20, 30, 50,
and 70H), 6.89 (m, 2H, Ar–20 and 50H), 6.80 (dd, 1H, J¼2.0
and 8.1 Hz, Ar–60H), 3.73 (s, 3H, OMe), 3.71 (s, 3H,
OMe), 3.57 (m, 2H, CH2), 2.85 (m, 2H, CH2); 13C NMR
(125 MHz, DMSO-d6): 168.6 (quat.), 148.8 (quat.), 147.5
(quat.), 135.4 (quat.), 133.3 (quat.), 132.1 (quat.), 129.9
(CH), 129.7 (CH), 128.3 (CH), 126.7 (CH), 126.5 (quat.),
126.3 (CH), 125.6 (CH), 125.0 (CH), 120.8 (CH), 112.9
(CH), 112.1 (CH), 55.7 (CH3), 55.5 (CH3), 40.9 (CH2),
34.8 (CH2); IR (KBr, cmꢂ1): 3335, 3001, 2956, 2938,
2914, 2835, 1633, 1619, 1592, 1538, 1518, 1461, 1329,
1291, 1265, 1201, 1161, 1025.
1
6.0; N, 4.4%]; H NMR (500 MHz, DMSO-d6): 8.00 (d,
1H, J¼8.3 Hz, Naph–40H), 7.98 (d, 1H, J¼8.3 Hz, Naph–
80H), 7.73 (dd, 1H, J¼1 and 8.3 Hz, Naph–50H), 7.59 (t,
1H, J¼8.3 Hz, Naph–60H), 7.51 (m, 2H, Naph–70 and 20H),
7.42 (dt, 1H, J¼1 and 8.3 Hz, Naph–30H), 7.02 (s, 1H, H-
8), 6.26 (s, 1H, H-5), 3.86 (m, 2H, H-3), 3.85 (s, 3H, OMe),
3.29 (s, 3H, OMe), 2.84 (m, 1H, H-4); 13C NMR
(125 MHz, DMSO-d6): 165.6 (quat.), 151.3 (quat.), 147.1
(quat.), 137.1 (quat.), 133.3 (quat.), 131.4 (quat.), 131.2
(CH), 128.7 (CH), 128.4 (quat.), 126.5 (CH), 126.3 (CH),
126.1 (CH), 125.7 (quat.), 125.4 (CH), 122.5 (CH), 111.25
(CH), 111.2 (CH), 55.8 (CH3), 55.7 (CH3), 47.5 (CH2),
25.3 (CH2); IR (KBr, cmꢂ1): 3013, 2933, 2896, 2830,
1604, 1564, 1510, 1464, 1456, 1432, 1353, 1318, 1277,
1262, 1236, 1213, 1197, 1163, 1131, 1057, 1040, 1017.
3.2.15. 6,7-Dimethoxy-1-(9H-9-fluorenylidenylmethyl)-
2-methoxycarbonylmethyl-3,4-dihydroisoquinolinium
bromide (14a). Compound 14a was prepared analogously to
8a from 13a (0.5 g, 1.36 mmol) and was isolated as a yellow
powder (0.71 g, 100%), mp 222–223 ꢀC; [Found: C, 64.6; H,
5.0; N, 2.7. C28H26NO4Br requires C, 64.6; H, 5.0; N, 2.7%];
1H NMR (500 MHz, CDCl3): 8.12 (d, 1H, J¼7.5 Hz, Flu–H),
7.62 (m, 3H, Flu–H), 7.46 (t, 1H, J¼7.5 Hz, Flu–H), 7.39 (d,
1H, J¼7.5 Hz, Flu–H), 7.28 (m, 1H, Flu–H), 7.10 (s, 1H,
H-8), 7.07 (s, 1H, H-5), 7.02 (s, 1H, CH]), 6.86 (d, 1H,
J¼7.5 Hz, Flu–H), 5.64 (d, 1H J¼17 Hz, NCH2), 5.13 (d,
3.2.13. 6,7-Dimethoxy-1-(9H-9-fluorenylidenmethyl)-
3,4-dihydroisoquinoline (13a). N-1-(30,40-Dimethoxyphen-
ethyl)-2-(9H-9-fluorenyliden)acetamide (8.0 g, 20.8 mmol)
was dissolved in dry toluene (50 ml) and freshly distilled
phosphorus oxychloride (3.15 g, 21 mmol) was added drop-
wise to the well-stirred mixture at 0 ꢀC. The reaction mixture
was stirred at reflux for 6 h, cooled to 5–10 ꢀC and then the
mixture was stirred with an excess of 10% aqueous sodium
hydroxide solution. The aqueous phase was washed with

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J. Toth et al. / Tetrahedron 62 (2006) 5725–5735
5733
1H, J¼17 Hz, NCH2), 3.84 (s, 3H, OMe), 3.78 (s, 3H, OMe),
3.72 (m, 2H, H-3), 3.59 (s, 3H, OMe), 3.28 (m, 2H, H-4); 13C
NMR (125 MHz, CDCl3): 179.0 (quat.), 166.1 (quat.), 158.1
(quat.), 149.0 (quat.), 145.0 (quat.), 144.6 (quat.), 142.3
(quat.), 140.6 (quat.), 140.1 (quat.), 134.4 (CH), 134.3
(quat.), 129.5 (CH), 129.3 (CH), 129.1 (CH), 128.4 (quat.),
127.5 (CH), 126.4 (CH), 123.0 (CH), 120.2 (CH), 119.7
(CH), 118.6 (quat.), 112.5 (CH), 111.5 (CH), 57.0 (CH3),
56.4 (CH3), 55.4 (CH2), 52.2 (CH3), 45.9 (CH2), 26.7
(CH2); IR (KBr, cmꢂ1): 3425, 2938, 2831, 1744, 1609,
1513, 1465, 1449, 1436, 1426, 1390, 1340, 1276, 1235,
1224, 1210, 1180, 1165, 1148, 1115, 1085, 1022.
1.57 mmol) and was isolated as a yellow powder (0.73 g,
100%); mp 211–212 ꢀC; [Found: C, 61.3; H, 5.2; N, 2.9.
C24H24NO4Br requires C, 61.3; H, 5.1; N, 3.0%]; 1H NMR
(500 MHz, DMSO-d6): 8.33 (d, 1H, J¼8.0 Hz, Naph–40H),
8.15 (d, 1H, J¼8.0 Hz, Naph–80H), 7.83 (dd, 1H, J¼1.5
and 8.0 Hz, Naph–50H), 7.80 (t, 1H, J¼8.0 Hz, Naph–60H),
7.65 (dt, 1H, J¼1.5 and 8 Hz, Naph–70H), 7.58 (dt, 1H,
J¼1.5 and 8.0 Hz, Naph–30H), 7.53 (d, 1H, J¼8.0 Hz,
Naph–20H), 7.47 (s, 1H, H-5), 6.17 (s, 1H, H-8), 4.80 (d,
1H, J¼17.1 Hz, NCH2), 4.64 (d, 1H, J¼17.1 Hz, NCH2),
4.59 (m, 1H, H-4), 4.48 (m, 1H, H-4), 4.03 (q, 2H,
J¼7.1 Hz, OCH2), 3.98 (s, 3H, OMe), 3.61 (m, 1H, H-3),
3.50 (m, 1H, H-3), 3.21 (s, 3H, OMe), 1.03 (t, 3H,
J¼7.1 Hz, CH3); 13C NMR (125 MHz, DMSO-d6): 174.6
(quat.), 165.8 (quat.), 157.8 (quat.), 148.0 (quat.), 135.8
(quat.), 133.0 (quat.), 132.5 (quat.), 129.1 (CH), 128.9
(CH), 128.5 (quat.), 127.6 (CH), 127.3 (CH), 126.2 (CH),
125.6 (quat.), 124.3 (CH), 119.4 (CH), 114.7 (CH), 112.1
(CH), 62.3 (CH2), 58.4 (CH2), 57.1 (CH3), 55.7 (CH3),
51.7 (CH2), 25.2 (CH2), 13.8 (CH3); IR (KBr, cmꢂ1): 3020,
3002, 2985, 1747, 1602, 1551, 1520, 1506, 1473, 1403,
1376, 1342, 1292, 1276, 1224, 1178, 1120, 1007.
3.2.16. 2-Benzyl-6,7-dimethoxy-1-(9H-9-fluorenylidenyl-
methyl)-3,4-dihydroisoquinolinium bromide (14b). Com-
pound 14b was prepared analogously to 8a from 13a (0.5 g;
1.36 mmol) and benzyl bromide (0.36 ml, 0.50 g, 3 mmol)
and was isolated as a yellow powder (0.71 g, 97%), mp
239–241 ꢀC; [Found: C, 71.3; H, 5.2; N, 2.6. C32H28NO2Br
1
requires C, 71.4; H, 5.2; N, 2.6%]; H NMR (500 MHz,
CDCl3): 8.12 (d, 1H, J¼7.5 Hz, Flu–H), 7.71 (m, 3H, Flu–
H), 7.52 (m, 2H, Ph–H), 7.44 (m, 3H, Ar–H and Flu–H),
7.30 (m, 2H, Ar–H), 7.22 (d, 1H, J¼7.5 Hz, Flu–H), 7.05
(s, 2H, H-8 and H-5), 6.85 (d, 1H, J¼7.5 Hz, Flu–H), 6.51
(s, 1H, CH]), 5.64 (d, 1H, J¼17.7 Hz, NCH2), 5.10 (d,
1H, J¼17.7 Hz, NCH2), 4.04 (s, 3H, OMe), 3.84 (s, 3H,
OMe), 3.58 (m, 2H, H-4), 3.48 (m, 2H, H-3); 13C NMR
(125 MHz, CDCl3): 171.6 (quat.), 157.6 (quat.), 148.9
(quat.), 146.2 (quat.), 142.8 (quat.), 140.4 (quat.), 136.7
(quat.), 134.1 (quat.), 133.5 (quat.), 131.3 (CH), 129.5
(2ꢁCH), 129.4 (CH), 129.2 (2ꢁCH), 129.0 (CH), 128.5
(CH), 128.3 (quat.), 127.9 (CH), 125.5 (CH), 123.3 (CH),
120.8 (CH), 120.3 (CH), 118.7 (quat.), 115.2 (CH), 114.0
(CH), 111.5 (CH), 62.0 (CH2), 57.2 (CH3), 56.4 (CH3),
49.7 (CH2), 26.4 (CH2); IR (KBr, cmꢂ1): 2955, 2938, 1602,
1551, 1496, 1451, 1386, 1338, 1293, 1271, 1219, 1170, 1004.
3.3. 1,7-Electrocyclizations—method B
The corresponding 6,7-dimethoxy-1-(9H-9-fluorenylidene-
methyl)-3,4-dihydroisoquinolinium bromide (0.75 mmol)
was dissolved in dry methanol (10 ml) and triethylamine
(0.11 ml, 1.5 mmol) was added. The reaction mixture was
stirred for 24 h at room temperature under an argon atmo-
sphere. The solvent was removed in vacuo, the residue was
dissolved in dichloromethane (15 ml) and washed with
water (2ꢁ10 ml) and brine (10 ml). The organic layer was
dried over magnesium sulfate and evaporated in vacuo.
The residue was further purified by column chromatography
on silica gel, eluting with hexane–acetone (3:1).
3.2.17. 2-Allyl-6,7-dimethoxy-1-(9H-9-fluorenyliden-
methyl)-3,4-dihydroisoquinolinium bromide (14c). Com-
pound 14c was prepared analogously to 8e from 13a (0.5 g,
1.36 mmol) and was isolated as a yellow powder (0.65 g,
98%), mp 233 ꢀC; [Found: C, 69.0; H, 5.2; N, 2.7.
C28H26NO2Br requires C, 68.9; H, 5.4; N, 2.9%]; 1H NMR
(500 MHz, CDCl3): 7.72 (d, 1H, J¼7.8 Hz, Flu–H), 7.67
(m, 1H, Flu–H), 7.41 (m, 3H, Flu–H), 7.25 (t, 1H,
J¼7.5 Hz, Flu–H), 7.17 (m, 2H, Flu–H), 7.07 (s, 2H, H-5
and H-8), 7.00 (s, 1H, CH]), 6.05 (d, 1H, J¼9.5 Hz, allyl),
5.47 (m, 1H, allyl), 5.24 (d, 1H, J¼18 Hz, NCH2), 5.13 (m,
1H, allyl), 4.85 (d, 1H, J¼18 Hz, NCH2), 4.02 (s, 3H,
OMe), 3.91 (m, 1H, H-3), 3.85 (s, 3H, OMe), 3.70 (m, 2H,
H-3 and H-4), 3.33 (m, 1H, H-4); 13C NMR (125 MHz,
CDCl3): 177.4 (quat.), 157.6 (quat.), 148.9 (quat.), 145.3
(quat.), 143.9 (quat.), 140.8 (quat.), 140.4 (quat.), 133.6
(quat.), 129.1 (CH), 128.9 (CH), 128.8 (CH), 128.3 (CH),
127.6 (CH), 127.4 (CH), 126.4 (CH2), 125.7 (quat.), 123.0
(CH), 125.3 (CH2), 120.8 (CH), 119.8 (CH), 116.2 (quat.),
112.4 (CH), 111.6 (CH), 80.5 (CH), 56.9 (CH3), 56.3 (CH3),
44.3 (CH2), 26.4 (CH2); IR (KBr, cmꢂ1): 2937, 1603, 1554,
1521, 1450, 1387, 1338, 1291, 1271, 1219, 1171, 1004.
3.3.1. Methyl 14,15-dimethoxy-1,2,4,12a-tetrahydro-
fluoreno[90,10:4,5,6]azepino[2,1-a]isoquinoline-4-carbox-
ylate (15a). Pale yellow oil, (0.16 g, 49%); 1H NMR
(500 MHz, CDCl3): 7.70 (m, 2H, H-5 and H-11), 7.56 (m,
2H, H-7 and H-8), 7.37 (m, 2H, H-6 and H-16), 7.31 (dt,
1H, J¼1.0 and 7.5 Hz, H-10), 7.21 (dt, 1H, J¼1.0 and
7.5 Hz, H-9), 6.98 (s, 1H, H-13), 6.69 (s, 1H, H-12), 5.00
(s, 1H, H-4), 4.42 (s, 1H, H-12a), 3.89 (s, 3H, OMe), 3.78
(s, 3H, OMe), 3.47 (m, 2H, H-1), 3.05 (s, 3H, OMe), 2.84
(m, 2H, H-2); 13C NMR (125 MHz, CDCl3): 169.8 (quat.),
150.4 (quat.), 149.7 (quat.), 148.0 (quat.), 147.8 (quat.),
147.0 (quat.), 141.0 (quat.), 139.7 (quat.), 129.1 (quat.),
128.0 (CH), 127.8 (CH), 127.6 (CH), 127.4 (CH), 127.2
(quat.), 125.6 (CH), 124.3 (CH), 120.0 (quat.), 119.7 (CH),
110.8 (CH), 107.5 (CH), 99.0 (CH), 77.3 (CH), 56.0
(CH3), 55.85 (CH3), 53.9 (CH), 51.3 (CH3), 47.8 (CH2),
29.3 (CH2); IR (neat, cmꢂ1): 2938, 2831, 1744, 1629,
1513, 1465, 1449, 1436, 1426, 1276, 1235, 1224, 1210,
1180, 1165, 1148, 1115, 1085, 1022; (HRMS Found: m/z
439.1747. C28H25NO4 m/z 439.1783).
3.3.2. 14,15-Dimethoxy-4-phenyl-1,2,4,12a-tetrahydro-
fluoreno[90,10:4,5,6]azepino[2,1-a]isoquinoline (15b).
Pale yellow oil, (0.16 g, 46%); 1H NMR (500 MHz,
CDCl3): 7.82 (m, 2H, H-5 and H-11), 7.61 (m, 2H, H-7 and
H-8), 7.40 (m, 5H, Ph–H and H-6, H-16), 7.21 (m, 2H, H-9
3.2.18. 6,7-Dimethoxy-1-(1-naphthyl)-2-ethoxycarbonyl-
methyl-3,4-dihydroisoquinolinium bromide (16). Com-
pound 16 was prepared analogously to 8a from 13b (0.5 g,

´
J. Toth et al. / Tetrahedron 62 (2006) 5725–5735
5734
and H-10), 7.08 (m, 2H, Ph–H), 6.76 (s, 1H, H-13), 6.73 (s,
1H, H-12), 5.21 (s, 1H, H-12a), 4.84 (s, 1H, H-4), 3.92 (s,
3H, OMe), 3.82 (s, 3H, OMe), 3.32 (m, 2H, H-1), 2.82 (m,
2H, H-2); 13C NMR (125 MHz, CDCl3): 149.9 (quat.),
148.2 (quat.), 147.7 (quat.), 147.1 (quat.), 146.2 (quat.),
142.3 (quat.), 140.0 (quat.), 133.4 (quat.), 129.7 (2ꢁCH),
129.4 (quat.), 128.9 (2ꢁCH), 128.3 (CH), 128.2 (CH),
127.9 (CH), 127.6 (CH), 127.5 (CH), 127.3 (quat.), 125.9
(CH), 124.8 (CH), 121.1 (CH), 119.9 (quat.), 111.0 (CH),
108.0 (CH), 101.8 (quat.), 80.2 (CH), 55.9 (CH3), 55.85
(CH3), 55.8 (CH), 45.9 (CH2), 29.2 (CH2); IR (neat, cmꢂ1):
2932, 2835, 1607, 1513, 1502, 1494, 1464, 1390, 1345,
1267, 1211, 1148, 1025; (HRMS Found: m/z 457.2040.
C32H27NO2 requires m/z 457.2042).
hyde (1.1 mmol) were dissolved in dry xylene (15 ml), the
reaction mixture was refluxed for 11–32 h and the water
formed was removed with the aid of a Dean–Stark trap. After
cooling, the solvent was removed in vacuo and the resulting
residue purified by column chromatography on silica, elut-
ing with hexane–acetone (90:10 to 50:50).
3.4.1. 2,3-Dimethoxy-13-phenyl-8-(4-chlorophenyl)-
5,6,8,14a-tetrahydrobenz[5,6]azepino[2,1-a]isoquinoline
1
(11k). Pale yellow oil (0.16 g, 32%); H NMR (500 MHz,
CDCl3): 7.50 (d, 2H, J¼7.5 Hz, Ar–H, H-20 and 60), 7.37–
7.22 (m, 5H, Ar–H), 7.18 (s, 1H, H-1), 7.01 (d, 2H,
J¼7.5 Hz, Ar–30 and 50H), 6.96 (m, 2H, Ar–H), 6.85 (m,
2H, Ar–H), 6.65 (s, 1H, H-14), 5.49 (s, 1H, H-14a), 5.14
(s, 1H, H-8), 3.91 (s, 3H, OMe), 3.89 (s, 3H, OMe), 3.85
(m, 2H, H2-6), 3.07 (m, 1H, H2-5), 2.89 (m, 1H, H2-5);
13C NMR (125 MHz, CDCl3): 152.7 (quat.), 150.2 (quat.),
147.9 (quat.), 144.2 (quat.), 141.2 (quat.), 140.1 (quat.),
137.8 (quat.), 136.6 (quat.), 129.5 (quat.), 129.2 (2ꢁCH),
128.5 (CH), 128.2 (2ꢁCH), 130.2 (2ꢁCH), 128.5
(2ꢁCH), 128.45 (2ꢁCH), 128.2 (CH), 128.0 (2ꢁCH),
120.3 (quat.), 111.0 (CH), 110.1 (CH), 104.7 (CH), 77.4
(CH), 56.2 (CH3), 56.1 (CH3), 45.0 (CH2), 30.0 (CH2); IR
(KBr, cmꢂ1): 2940, 2921, 2910, 2845, 1611, 1501, 1460,
1337, 1319, 1296, 1271, 1212, 1177, 1149, 1111, 1029;
(HRMS Found: m/z 493.1803. C32H28NO2Cl requires m/z
493.1809).
3.3.3. 14,15-Dimethoxy-4-ethenyl-1,2,4,12a-tetrahydro-
fluoreno[90,10:4,5,6]azepino[2,1-a]isoquinoline (15c).
Pale yellow oil, (0.13 g, 44%); 1H NMR (500 MHz,
CDCl3): 7.72 (m, 2H, H-5 and H-11), 7.41 (m, 3H, H-6,
H-7 and H-8), 7.27 (s, 1H, H-16), 7.22 (m, 2H, H-9 and H-
10), 7.09 (s, 2H, H-12 and H-13), 6.03 (d, 1H, J¼9.3 Hz,
H-4), 5.47 (m, 1H, vinyl–CH), 5.17 (d, 1H, J¼18 Hz, vinyl–
CH2), 5.11 (s, 1H, H-12a), 4.85 (d, 1H, J¼18 Hz, vinyl–
CH2), 4.32 (m, 1H, H-1), 4.02 (s, 3H, OMe), 3.84 (s, 3H,
OMe), 3.68 (m, 2H, H-1 and H-2), 3.36 (m, 1H, H-2); 13C
NMR (125 MHz, CDCl3): 150.1 (quat.), 147.9 (quat.),
147.7 (quat.), 147.5 (quat.), 147.1 (quat.), 143.1 (quat.),
139.5 (quat.), 129.7 (quat.), 128.6 (CH), 127.7 (CH), 127.6
(2ꢁCH), 127.3 (CH), 127.2 (quat.), 126.3 (CH2), 126.1
(CH), 124.9 (CH), 121.4 (CH), 119.8 (quat.), 110.7 (CH),
107.9 (CH), 102.1 (CH), 79.2 (CH), 59.9 (CH), 55.8 (CH3),
55.7 (CH3), 46.0 (CH2), 29.2 (CH2); IR (neat, cmꢂ1): 3387,
2937, 1711, 1604, 1559, 1524, 1450, 1421, 1397, 1337,
1291, 1220, 1164, 1083, 1006; (HRMS Found: m/z
407.1907. C28H25NO2 requires m/z 407.1885).
3.4.2. 2,3-Dimethoxy-13-phenyl-8-(4-methoxyphenyl)-
5,6,8,14a-tetrahydrobenz[5,6]azepino[2,1-a]isoquinoline
1
(11l). Pale yellow oil (0.13 g, 26%); H NMR (500 MHz,
CDCl3): 7.53 (d, 2H, J¼7.5 Hz, Ar8-20 and 60H), 7.34–7.15
(m, 7H, Ar–H), 7.01 (m, 3H, Ar–H), 6.90 (m, 3H, Ar–H),
6.66 (s, 1H, H-14), 5.54 (s, 1H, H-14a), 5.12 (s, 1H, H-8),
3.89 (s, 3H, OMe), 3.87 (s, 3H, OMe), 3.77 (m, 2H, H2-6),
3.00 (m, 1H, H2-5), 2.74 (m, 1H, H2-5); 13C NMR
(125 MHz, CDCl3): 162.8 (quat.), 149.6 (quat.), 147.3
(quat.), 144.8 (quat.), 142.5 (quat.), 141.1 (quat.), 137.6
(quat.), 133.2 (2ꢁCH), 129.0 (2ꢁCH), 128.2 (quat.), 128.1
(2ꢁCH), 128.0 (CH), 127.7 (CH), 127.4 (CH), 127.3 (CH),
126.3 (CH), 126.1 (quat.), 120.0 (quat.), 112.7 (2ꢁCH),
110.8 (CH), 109.9 (CH), 103.0 (CH), 77.6 (CH), 56.0
(CH3), 55.8 (CH3), 45.3 (CH2), 29.6 (CH2); IR (KBr, cmꢂ1):
2963, 2836, 1604, 1559, 1513, 1464, 1399, 1258, 1168,
1113, 1028; (HRMS Found: m/z 489.2324. C33H31NO3
requires m/z 489.2303).
3.3.4. 1-(2,2-Diphenylethenyl)-6,7-dimethoxy-1,2,3,4-tetra-
hydroisoquinoline (16). 6,7-Dimethoxy-1-(20,20-diphenyl-
1-ethenyl]-3,4-dihydroisoquinoline (3.73 g, 10 mmol) was
dissolved in ethanol (50 ml) and sodium borohydride (1.89 g,
50 mmol) was added in small portions. The mixture was
refluxed for 1 h, then the solvent was removed in vacuo. The
residue was dissolved in dichloromethane (100 ml) and
washed with water (2ꢁ50 ml) and brine (30 ml). The organic
layer was dried over magnesium sulfate and evaporated
in vacuo to give a white semi-solid product (3.71 g, 100%).
1H NMR (500 MHz, CDCl3): 7.41–7.23 (m, 10H, Ph), 6.63
(s, 1H, H-5), 6.58 (s, 1H, H-8), 6.20 (d, 1H, J¼9.6 Hz,
CH]), 4.58 (d, 1H, J¼9.6 Hz, H-1), 3.82 (s, 3H, OMe), 3.79
(s, 3H, OMe), 3.27 (m, 1H, H2-4), 2.90 (m, 1H, H2-4), 2.63
(m, 2H, H2-3); 13C NMR (125 MHz, CDCl3): 147.7 (quat.),
147.3 (quat.), 143.6 (quat.), 141.9 (quat.), 139.6 (quat.), 130.7
(quat.), 129.7 (2ꢁCH), 129.6 (quat.), 128.6 (2ꢁCH), 128.3
(2ꢁCH), 127.6 (CH), 127.5 (3ꢁCH), 126.9 (CH), 111.9
(CH), 110.4 (CH), 56.0 (CH3), 55.9 (CH3), 55.5 (CH), 42.4
(CH2), 29.2 (CH2); IR (KBr, cmꢂ1): 3047, 3023, 3000, 2958,
2921, 2826, 1599, 1575, 1509, 1466, 1446, 1427, 1369, 1329,
1281, 1265, 1218, 1126, 1033; (HRMS: Found: m/z
371.1872. C25H25NO2 requires m/z 371.1885).
3.4.3. 2,3-Dimethoxy-13-phenyl-8-(3,4-methoxyphenyl)-
5,6,8,14a-tetrahydrobenz[5,6]azepino[2,1-a]isoquinoline
(11m). Pale yellow oil, 0.06 g (11%); H NMR (500 MHz,
1
CDCl3): 7.52 (m, 2H, Ar–H), 7.33 (m, 2H, Ar–H), 7.24
(m, 3H, Ar–H), 7.06 (m, 4H, Ar–H), 6.88 (m, 3H, Ar–H),
6.66 (s, 1H, H-14), 6.14 (s, 1H, H-14a), 5.47 (s, 1H, H-8),
3.93 (s, 3H, OMe), 3.90 (s, 3H, OMe), 3.81 (s, 6H,
2ꢁOMe), 3.39 (m, 2H, H2-6), 3.05 (m, 1H, H2-5), 2.63
(m, 1H, H2-5); 13C NMR (125 MHz, CDCl3): 149.2 (quat.),
149.1 (quat.), 148.8 (quat.), 147.1 (quat.), 144.9 (quat.), 143.9
(quat.), 143.0 (quat.), 137.2 (quat.), 129.1 (quat.), 128.8
(2ꢁCH), 128.5 (CH), 128.4 (CH), 128.0 (CH), 127.8
(2ꢁCH), 127.5 (2ꢁCH), 127.25 (CH), 127.2 (quat.), 120.0
(quat.), 119.3 (CH), 112.7 (CH), 112.0 (CH), 110.8 (CH),
109.9 (CH), 102.9 (CH), 77.5 (CH), 56.0 (CH3), 55.9
(2ꢁCH3), 55.8 (CH3), 45.4 (CH2), 29.6 (CH2); IR (KBr,
3.4. 1,7-Electrocyclization—method C
1-(2,2-Diphenylethenyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-
isoquinoline (0.37 g, 1 mmol) and the corresponding alde-

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J. Toth et al. / Tetrahedron 62 (2006) 5725–5735
5735
cmꢂ1): 2937, 2836, 1603, 1514, 1495, 1464, 1399, 1268,
1147, 1025; (HRMS Found: m/z 519.2398. C34H33NO4
requires m/z 519.2409).
6. (a) Groundwater, P. W.; Sharif, T.; Arany, A.; Hibbs, D. E.;
Hurthouse, M. B.; Nyerges, M. Tetrahedron Lett. 1998, 39,
1433–1436; (b) Groundwater, P. W.; Sharif, T.; Arany, A.;
Hibbs, D. E.; Hurthouse, M. B.; Garnett, I.; Nyerges, M.
J. Chem. Soc., Perkin Trans. 1 1998, 2837–2846.
Acknowledgements
7. Nyerges, M.; Arany, A.; Fejes, I.; Groundwater, P. W.; Zhang,
W.; Bendell, D.; Anderson, R. J.; TTke, L. Tetrahedron 2002,
58, 989–995.
This work was financially supported by the National Fund
for Science and Research, Hungary (OTKA Project No.
T 046196). N.M. thanks the Hungarian Academy of Sci-
´
8. (a) Nyerges, M.; Fejes, I.; Viranyi, A.; Groundwater, P. W.;
TTke, L. Tetrahedron Lett. 2001, 42, 5081–5083; (b) Nyerges,
´
ences for a Bolyai J. fellowship. A grant from the Jozsef
Varga Foundation provided to J.T. is gratefully appreciated.
´
´
M.; Viranyi, A.; Zhang, W.; Groundwater, P. W.; Blasko, G.;
TTke, L. Tetrahedron 2004, 60, 9937–9944.
9. A part of this work has been published in preliminary form:
´
´
´
Nyerges, M.; Viranyi, A.; Pinter, A.; TTke, L. Tetrahedron
Lett. 2003, 44, 793–794.
10. (a) Harmon, R. E.; Jensen, B. L.; Gupta, S. X.; Nelson, J. D.
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2000, 56, 639–644; (g) Nyerges, M.; Somfai, B.; Toth, J.;
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Dancso, A.; Blasko, G.; TTke, L. Synthesis 2005,
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¨
¨
5. (a) Arany, A.; Groundwater, P. W.; Nyerges, M. Tetrahedron
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