1,6-Electrocyclization of 1-azatriene derivatives

Article abstract of DOI:10.1002/ejoc.200700913

1-Cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinium mesylate (10) readily reacted with α,β-unsaturated aldehydes to afford 1-azatrienes 12a-h, which could be cyclized to give 6,7-dihydro-4H-benzo[a] quinolizines 14a-h. The reaction mechanisms were investigated by computational methods. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200700913

FULL PAPER
DOI: 10.1002/ejoc.200700913
1,6-Electrocyclization of 1-Azatriene Derivatives
Zoltán Vincze,[a] Zoltán Mucsi,[a] Pál Scheiber,[a] and Péter Nemes*[a]
Keywords: 1-Azatrienes / (E)Ǟ(Z) isomerization / Electrocylization / Activation parameters / 6,7-Dihydro-4H-benzo[a]-
quinolizines
1-Cyanomethylene-6,7-dimethoxy-1,2,3,4-tetrahydroiso-
quinolinium mesylate (10) readily reacted with α,β-unsatu-
rated aldehydes to afford 1-azatrienes 12a–h, which could be
cyclized to give 6,7-dihydro-4H-benzo[a]quinolizines 14a–h.
The reaction mechanisms were investigated by computa-
tional methods.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
underwent base-catalyzed Michael reactions with various
α,β-unsaturated carbonyl compounds 2, followed by spon-
taneous cyclization to furnish different 6,7-dihydro-2H-
benzo[a]quinolizine derivatives 3.[4]
Introduction
Polycyclic N-heterocycles containing 1,2-fused tetra-
hydroisoquinoline moieties constitute the basic structural
frameworks of various naturally occurring alkaloids and
biologically active drugs.[1] Although several methods for
the preparation of these heterocycles are known,[2] due to
their great significance the development of new and efficient
synthetic routes to this class of compounds might be of
strong relevance.
Push-pull enamines, especially β-enaminonitriles, have
proved in a number of cases to be valuable starting materi-
als in the synthesis of various N-heterocycles.[3] We have
previously reported that the readily accessible -cyano-
methylene-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (1)
Surprisingly, the microwave-mediated transformation of
the same starting compounds afforded 6,7-dihydro-4H-
benzo[a]quinolizines 4, with reversed regioselectivity.[5]
Furthermore, in the presence of cerium(III) chloride the en-
aminonitrile 1 reacted with α,β-unsaturated aldehydes 2 to
yield benzo[a]quinolizines 5, while with α-alkyl-substituted
unsaturated aldehydes (2, R1 = CH3), pyrrolo[2,1-a]iso-
quinolines 6 were obtained (Scheme 1).[6] In view of these
interesting results, here we discuss the scope and the mecha-
nism of the microwave-activated cyclisations of 1 and α,β-
unsaturated aldehydes.
Scheme 1. Reactions of 1 with aldehydes.
Computational Methods
[a] Department of Chemistry, Faculty of Veterinary Science, Szent
István University,
The B3LYP/6-31G(d)[7] and MP2/6-31G(d)//B3LYP/6-
31G(d) levels of theory were used in this work, with 9ϫ5
= 45 structures being optimized at the B3LYP/6-31G(d)
level of theory in vacuo and in solvent (CH2Cl2), by use
of the default PCM method (IEF-PCM, integral equation
P. O. Box 2, 1400 Budapest, Hungary
Fax: +36-1-4784268
E-mail: Nemes.Peter@aotk.szie.hu
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Eur. J. Org. Chem. 2008, 1092–1100

1,6-Electrocyclization of 1-Azatriene Derivatives
formalism polarizable continuum medium; PCM in brief) ried out in acetic acid at room temperature (Table 1). Be-
(Table 3) and the Gaussian 03 program.[8] The enthalpies cause of their low stabilities, compounds 12a–h were stored
and Gibbs free energies were calculated at 298.14 K.
at low temperature (–4 ᭺C).
Table 1. Formation of the azatrienes in acetic acid.
R1
R2
Time [h]
Yield [%]
Results and Discussion
Product
12a
12b
12c
12d
12e
12f
12g
12h
H
CH3
H
CH3
H
CH3
H
CH3
H
H
2
6
2
7
3
9
2
8
92
87
82
65
76
67
89
71
As we suggested earlier, in the microwave-promoted reac-
tions the nucleophilic addition takes place on the C1Ј car-
bon atom of enaminonitrile 1, and the formed adduct 8 is
transformed into 6,7-dihydro-4H-benzo[a]quinolizine 9 in a
subsequent ring-closure reaction (Scheme 2).[5]
NO2
NO2
OMe
OMe
NMe2
NMe2
With addition of TEA in excess to the MeCN solutions
of azatrienes 12b, 12d, 12f, and 12h (R1 = CH3), the cycliza-
tion took place at room temp. to give 6,7-dihydro-4H-
benzo[a]quinolizines 14b, 14d, 14f, and 14h, while azatrienes
12a, 12c, 12e, and 12g (R1 = H) could be cyclized only in
MeCN at reflux (Scheme 4, Table 2). Noteworthy about the
cyclizations of the azatrienes are the mild reaction condi-
tions under which the ring-closure reaction occurs. In con-
trast, the electrocyclization of all-carbon triene analogues
requires high temperatures (typically Ͼ130 ᭺C).[11]
Scheme 2. Proposed mechanism of the microwave-activated ring-
closure reaction.
Synthesis
In order to obtain the intermediate 8, the mesylate salt
of 1 (10) was prepared and used in the microwave-mediated
reaction with α,β-unsaturated aldehydes 11a–h (Scheme 3).
In these solvent-free Knoevenagel-type condensations, pro-
tonated 1-azatrienes 12a–h were obtained. The (E,E) con-
figurations of the double bonds were determined by NMR
(J-HMBC, J-INEPT)[9,10] methods.
Despite the fairly short microwave irradiation times ap-
plied (1 min), considerable decomposition of the azatrienes
was observed. Higher yields were achieved, and the purifi-
cation procedure was simple, when the reactions were car-
Table 2. Ring-closure reaction of 1-azatriene derivatives.
Product
R1
R2
Time [h]
Temp.
Yield [%]
14a
14b
14c
14d
14e
14f
14g
14h
H
CH3
H
CH3
H
CH3
H
CH3 N(Me)2
H
H
NO2
NO2
OMe
OMe
N(Me)2
2
4
5
8
3
2
1
1
reflux
room temp.
reflux
room temp.
reflux
room temp.
reflux
room temp.
85
82
75
72
69
65
89
82
Scheme 3. Preparation of 1-azatrienes.
Scheme 4. 1,6-Electrocyclisation of 1-azatriene derivatives 12a–h.
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FULL PAPER
In addition to the effect of the methyl group in the C3Ј
In our computations, no direct saddle point could be
positions of azatrienes 12b, 12d, 12f, and 12h, the reaction found for the (E)Ǟ(Z) isomerization step of 12, leading to
rates were also affected by the substituents at the para posi- 18, and all optimizations led to dihydroazete intermediates
tions of the phenyl rings. For the cyclization of 12d, with 17a–h. Each overall process, involving an intermediate
the electron-withdrawing nitro group, the reaction time was (17a–h) and two TSs (TS17a–h and TS18Aa–h), requires an
longer than for the unsubstituted compound 12b. In con- activation energy (TS18A; ∆G‡
=
165–174 kJmol–1;
trast, the electron-donating substituents in 12f and 12h Table 3) significantly lower than that of the all-carbon hexa-
shortened the reaction times. Similar tendencies could be triene analogue 19 (∆G‡ = 225 kJmol–1; Figure 2). The rela-
ascertained for the compounds 12a, 12c, and 12g (R1 = H) tively low energy differences between compounds 12 and
in acetonitrile at reflux, but in the case of azatriene 12e the compounds 17 (57–83 kJmol–1; Figure 3), and conse-
presumed accelerating effect was not observed (Table 2).
quently the formation of 17a–h, can be explained by the
For 6π-electrocyclization to be able to take place, the aza- low ring-strain enthalpies (46.0–48.6 kJmol–1 for 17a), cal-
trienes must possess the appropriate geometry. Conse- culated from the isodesmic reaction enthalpies (see Sup-
quently, the first step of the process must be an (E)Ǟ(Z) porting Information). Furthermore, the computations re-
isomerization, in which the electron-withdrawing CN group veal that the process is promoted by a nucleophilic intramo-
plays a crucial role. To confirm this assumption we at- lecular attack of the nitrogen atom on the electron-poor C2Ј
tempted to cyclize the 1-azatriene derivative 15 (Scheme 5), atom, favoring a nucleophilic cyclisation process in which,
prepared by known methods.[12]
beside the π-electrons of the two double bonds (N2=C1 and
C1Ј=C2Ј), the nonbonding electron pair of the N atom is
also involved (Scheme 6). In order to check the results of
the B3LYP/6-31G(d) method, a more reliable MP2/6-
31G(d)//B3LYP/6-31G(d) level of theory[13,14] was also uti-
lized for the reaction sequence 12a Ǟ 14a. The energies
calculated in this way are close to the values obtained by
the DFT method [B3LYP/6-31G(d)], and only the ∆G‡ val-
ues of TSs in the isomerization steps (TS17a, TS18Aa,
TS18Ba) proved to be significantly higher, by roughly
10 kJmol–1. For this reason, the B3LYP/6-31G(d) level of
theory was applied for other derivatives.
Scheme 5. Attempted cyclization of 15.
This compound, with no CN group in the C1Ј position,
failed to undergo ring-closure reaction to 16 in the presence
of TEA, even on heating at reflux in xylene for 24 h.
The calculated Nucleus-Independent Chemical Shift
(NICS) values,[15] measures of the aromaticity forming in
the transition state, are –5.6 and –4.6 ppm for TS17a and
TS18Aa, respectively, indicating a moderate aromatization
during the ring-closure and ring-opening reactions. The
NICS value for the TS of butadiene Ǟ cyclobutene is
–12.3 ppm.[16] The participation of the nonbonding electron
Mechanism of the Cyclization of 1-Azatrienes
Since the NMR spectroscopic data unambiguously pair of the N atom may be confirmed by the HOMOs of
showed (E,E) configurations of the double bonds in com- TS17a and TS18Aa. In both cases, the nonbonding electron
pounds 12a–h, the first step of the reaction must be an pair of the N atom is strongly involved in the HOMOs of
(E)Ǟ(Z) isomerization (Scheme 6 and Figure 1).
the transition states (Figure 4).
Scheme 6. Proposed mechanism for the transformations of 12a–h into 14a–h. The italic numbers in 18Ba–h indicate the atomic natural
bond orbital (NBO) charges of atoms in 18Ba.
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1,6-Electrocyclization of 1-Azatriene Derivatives
Figure 1. Ball-and-stick representation of the reaction sequence 12a Ǟ 17a Ǟ 18Aa Ǟ 18Ba Ǟ 14a (hydrogen atoms are ignored).
Table 3. ∆G values [kJmol–1] for compounds and transition states involved in the mechanism.
(E)Ǟ(Z) isomerization step
Conformational step
Ring-closure step
R1
R2
12
TS17
17
TS18A
18A
TS18B
18B
TS14
14
12a
12a[a]
12b
12c
12g
19
H
H
Me
H
H
H
H
H
H
NO2
NMe2
H
0.00
0.00
0.00
0.00
0.00
0.00
147.75
161.04
132.56
150.01
142.10
186.46
80.63
95.31
61.67
77.30
84.14
117.65
173.78
186.66
165.47
173.62
172.68
210.82
8.37
9.78
11.57
7.13
4.35
9.13
46.83
38.64
26.51
45.20
54.95
43.358
31.63
29.55
17.74
31.06
30.15
32.01
102.61
96.57
89.29
103.61
95.63
115.80
–10.67
–40.98
–46.70
7.13
–6.26
7.98
[a] Computed at the MP2/6-31G(d)//B3LYP/6-31G(d) level of theory.
structures 17a–h should be involved as intermediates in the
isomerization process. The intermediates 17 can readily un-
dergo ring-opening reaction to give 18A with a (Z,E) con-
figuration.
Besides the synthetic verification, computational results
showed unequivocally that the electron-withdrawing CN
group significantly influences the reaction rates of all
steps.[17] As the natural bond orbital (NBO) charges (18B
in Scheme 6) indicate, the CN group lowers the electron
density at the C2Ј and C4Ј atoms, promoting the nucleo-
philic attack of the N2 atom and decreasing all activation
parameters (Figure 3, Table 3).
To achieve the optimal molecular geometry, a rotation
takes place around the C2Ј–C3Ј single bond, with a low en-
ergy barrier (Figure 2, Table 3). The subsequent cyclization
of the 1-azatrienes 18Ba–h seems to be a classical 6π-elec-
trocyclic mechanism. However, the calculated NICS
Figure 2. Gibbs free energy [kJmol–1] diagram for the isomerization
of 12 and hypothetical C2 analogue 19.
In order to obtain more evidence for the nitrogen partici- value[18] for TS14a is only –5.1 ppm. This value is signifi-
pation, the 3D potential surface was computed at the cantly lower than the similarly calculated NICS value in
HF/3-21G level of theory (Figure 5). The absence of a first- the ring-closure reaction of cyclohexatriene [–14.5 ppm at
order saddle point between 12 and 18A in the 3D cross- B3LYP/6-31G(d)], which may be considered a pure electro-
section unambiguously shows that the 1,2-dihydroazete cyclization. From these data, one may conclude that the
Eur. J. Org. Chem. 2008, 1092–1100
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Z. Vincze, Z. Mucsi, P. Scheiber, P. Nemes
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Figure 3. Computed Gibbs free energy [kJmol–1] diagram for the mechanism of the transformation 12a Ǟ 14a.
Figure 4. Schematic representation of the HOMO and LUMO atomic orbitals of TS17a, 18Aa, and TS14a (nb refers to the nonbonding
electron pair of the N atom).
cyclization step takes place with a mixed mechanism, com- may support its participation in the reaction (Figure 4). Be-
posed of a nucleophilic attack of the N1 atom on the elec- cause the position of the N atom is fixed by the tetrahydro-
tron-poor C4Ј atom (see NBO charges of 18B in Scheme 6), isoquinoline ring, the C1Ј–C1=N2–C3 torsion angle does not
and a 6π-electrocyclization process (Scheme 7). The strong change (ca. 3°) during the reaction, in contrast with the
involvement of the nonbonding electron pair of the N atom significant rotation of the C2–C3=C4–CPh torsion angle (ca.
in the HOMO and not in the LUMO of TS14, where the 35°; Figure 1). Consequently, the process can not be re-
LUMO is instead dominated by the C1=N2 double bond, garded either as a disrotatory or a conrotatory mechanism.
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1,6-Electrocyclization of 1-Azatriene Derivatives
Scheme 7. Schematic representation of the proposed mixed mechanism for the ring-closure step, involving a nucleophilic attack of the N
atom and a 6π-electrocyclisation.
The electron-donating NMe2 group (12g) decreases, while
the electron-withdrawing NO2 group (12c) increases the ac-
tivation parameters of the ring-closure reaction.
Conclusions
A new method has been developed for the synthesis of
1-azatrienes 12a–h, which could be isolated and cyclized to
6,7-dihydro-4H-benzo[a]quinolizines 14a–h. We have sug-
gested that the presence of the electron-withdrawing CN
group plays an important role in the 6π-aza electrocycliza-
tion. We found that the rate of cyclization is influenced
mainly by the presence of a methyl group in the C3Ј position
and the substituents at the para position in the phenyl ring,
in accordance with the computational results. The acti-
vation parameters of the cyclization were calculated, and
we have proposed a mechanism for the formation of 6,7-
Figure 5. Computed 3D PES for 12a Ǟ 17a Ǟ 18Aa.
dihydro-4H-benzo[a]quinolizines.
Since the direction of the rotation of the torsion angle
C2–C3=C4–CPh is not specified, the reaction is therefore not
stereoselective.
Experimental Section
General: All melting points were measured with a Büchi SMP-20
melting point apparatus and are uncorrected. NMR spectra were
recorded with a Bruker DRX 250 spectrometer (1H: 250 MHz; 13C:
62.5 MHz). The HPLC-MS analyses were performed with a PE
API 2000 apparatus. IR spectra were recorded with a Perkin–Elmer
series 1600 FT/IR spectrometer. Column chromatography was con-
ducted with Merck Kieselgel 60 (0.063–0.100 mm). Solvents were
dried and freshly distilled according to the common practice.
The computational studies also showed considerable sub-
stituent effects in the cyclization sequence. The presence of
an Me group in the C3Ј position (R1 = CH3, 12b) decreases
the activation parameters of all the steps by ca. 10–
20 kJmol–1, increasing the overall reaction rate signifi-
cantly. Moreover, it decreases the energy difference between
12b and 18Ab as well as between 18Ab and 18Bb. Finally,
it is noteworthy that the Me substitution also lowers the General Procedure for the Microwave-Assisted Synthesis of 1-Azatri-
enes 12a and 12b: 1-Cyanomethyl-6,7-dimethoxy-3,4-dihydroiso-
quinolinium mesylate (10, 500 mg, 1.54 mmol) was mixed with the
α,β-unsaturated aldehyde (11a, 11b, 3.08 mmol), and the mixture
was irradiated in an open vessel in a Synthewave S402 (Prolabo)
monomode, focused MW (2.45 GHz) reactor with continuous rota-
tion for 1 min. During the irradiation, the temperature of the reac-
tion mixture (measured by infrared thermometry) increased lin-
early, and reached 95 °C after 1 min. The oily material was then
cooled, and the product was crystallized from diisopropyl ether.
The crude product was purified by flash chromatography (silica gel,
energy content of the product 14b. From these data, we may
conclude that the electron donor character dominates the
overall effect of the Me group, and because of its relatively
large distance from the reaction center the steric hindrance
is less significant. The energy differences between the Me-
substituted and unsubstituted rotamers, 18Ab and 18Bb;
18Aa and 18Ba respectively, however, can undoubtedly be
explained by the steric effect of the Me group (Table 3).
The para substituents on the phenyl group modify all
activation parameters of the reaction sequence (Table 3). EtOAc). Yield: 45% (12a), 35% (12b).
Eur. J. Org. Chem. 2008, 1092–1100
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General Procedure for the Synthesis of 1-Azatrienes in Acetic Acid
(12a–h): The α,β-unsaturated aldehyde (11a–h, 3.0 mmol) was
added to a solution of 1-cyanomethyl-6,7-dimethoxy-3,4-dihydro-
isoquinolinium mesylate (10, 670 mg, 2 mmol) in glacial acetic acid
(6 mL). The reaction mixture was stirred at room temperature for
2–9 h. The solution was then poured into diisopropyl ether
(30 mL). The formed precipitate was filtered off and washed with
diethyl ether.
1-{1-Cyano-4-[4-(dimethylamino)phenyl]buta-1,3-dienyl}-6,7-dimeth-
oxy-3,4-dihydroisoquinolinium Mesylate (12g): Dark blue crystals,
yield: 860 mg (1.78 mmol, 89%). M.p. 132 °C (decomp.). 1H NMR
(CDCl3, 250 MHz): δ = 2.84 (s, 3 H, MeSO3), 3.02 (t, J = 7.5 Hz,
2 H, 4-H), 3.16 (s, 6 H, H-NMe2), 3.92 (t, J = 7.5 Hz, 2 H, H-3),
3.98 (s, 3 H, OMe), 4.02 (s, 3 H, OMe), 6.70 (d, J = 9.3 Hz, 2 H,
C6H4NMe2), 6.84 (s, 1 H, 5-H), 7.29 (dd, J1 = 14.4, J2 = 11.6 Hz,
1 H, 3Ј-H), 7.60 (s, 1 H, H-8), 7.67 (d, J = 9.3 Hz, 2 H,
C6H4NMe2), 7.95 (d, J = 14.4 Hz, 1 H, 4Ј-H), 8.75 (d, J = 11.6 Hz,
1 H, 2Ј-H) ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 26.1 (C-4),
39.2 (MeSO3), 40.1 (C-3), 40.5 (NMe2), 56.1 (OMe), 56.3 (OMe),
93.1 (C-1Ј), 110.7 (C-5), 112.1 (C-8), 112.7 (CN), 116.7 (C-9), 119.0
(C6H4NMe2), 123.2 (C-3Ј), 125.0 (C6H4NMe2), 133.1 (C-10), 134.6
(C6H4NMe2), 148.0 (C6H4NMe2), 153.5 (C-7), 155.7 (C-4Ј), 157.9
(C-6), 160.7 (C-2Ј), 165.6 (C-1) ppm.
1-(1-Cyano-4-phenylbuta-1,3-dienyl)-6,7-dimethoxy-3,4-dihydroiso-
quinolinium Mesylate (12a): Orange crystals, yield: 810 mg
(1.84 mmol, 92%). M.p. 75–76 °C (decomp.). 1H NMR (CDCl3,
250 MHz): δ = 2.84 (s, 3 H, MeSO3), 3.09 (t, J = 8.0 Hz, 2 H, 4-
H), 3.86 (t, J = 8.0 Hz, 2 H, 3-H), 4.03 (s, 3 H, OMe), 4.05 (s, 3
H, OMe), 6.88 (s, 1 H, 5-H), 7.27 (s, 1 H, 8-H), 7.42–7.55 (m, 5 H,
Ph), 7.71 (dd, J1 = 15.2, J2 = 11.5 Hz, 1 H, 3Ј-H), 7.93 (d, J =
15.2 Hz, 1 H, 4Ј-H), 8.78 (d, J = 11.5 Hz, 1 H, 2Ј-H) ppm. 13C
NMR (CDCl3, 62.5 MHz): δ = 26.1 (C-4), 39.8 (MeSO3), 41.7 (C-
3), 56.8 (OMe), 57.2 (OMe), 101.0 (C-1Ј), 111.7 (C-5), 113.0 (C-8),
115.4 (CN), 116.5 (C-9), 123.8 (C-3Ј), 129.6 (Ph), 129.8 (Ph), 132.6
(Ph), 135.0 (Ph), 135.8 (C-10), 148.9 (C-7), 155.0 (C-4Ј), 157.5 (C-
6), 161.1 (C-2Ј), 165.9 (C-1) ppm.
1-{1-Cyano-4-[4-(dimethylamino)phenyl]-3-methylbuta-1,3-dienyl}-
6,7-dimethoxy-3,4-dihydroisoquinolinium Mesylate (12h): Dark red
crystals, yield: 706 mg (1.42 mmol, 71%). M.p. 130 °C (decomp.).
1H NMR (CDCl3, 250 MHz): δ = 2.33 (s, 3 H, CH3), 2.58 (s, 3 H,
MeSO3), 3.08 (s, 6 H, NMe2), 3.88 (t, J = 6.3 Hz, 2 H, 4-H), 3.97
(s, 3 H, OMe), 4.00 (s, 3 H, OMe), 4.48 (t, J = 6.3 Hz, 2 H, 3-H),
6.87 (s, 1 H, 5-H), 7.26 (d, J = 8.7 Hz, 2 H, C6H4NMe2), 7.26 (s,
1 H, 8-H), 7.45 (d, J = 8.7 Hz, 2 H, C6H4NMe2), 7.97 (s, 1 H, 4Ј-
H), 8.47 (s, 1 H, 2Ј-H) ppm. 13C NMR (CDCl3, 62.5 MHz): δ =
20.1 (Me), 26.7 (C-4), 39.0 (MeSO3), 40.3 (NMe2), 52.6 (C-3), 56.2
(OMe), 56.3 (OMe), 107.8 (C-1Ј), 109.9 (C-5), 111.7 (C-8), 112.7
(CN), 115.8 (C-9), 117.3 (C6H4NMe2), 117.5 (C-3Ј), 129.8
(C6 H4 NMe2 ), 131.9 (C-10), 136.1 (C6 H4 NMe2 ), 148.3
(C6H4NMe2), 149.3 (C-7), 150.1 (C-4Ј), 151.1 (C-6), 153.9 (C-2Ј),
159.6 (C-1) ppm.
1-(1-Cyano-3-methyl-4-phenylbuta-1,3-dienyl)-6,7-dimethoxy-3,4-di-
hydroisoquinolinium Mesylate (12b): Yellow crystals, yield: 790 mg
1
(1.74 mmol, 87%). M.p. 132 °C (decomp.). H NMR (CDCl3, 250
MHz): δ = 2.48 (s, 3 H, Me), 2.84 (s, 3 H, MeSO3), 3.19 (t, J =
7.9 Hz, 2 H, 4-H), 3.88 (t, J = 7.9 Hz, 2 H, 3-H), 3.90 (s, 3 H,
OMe), 3.94 (s, 3 H, OMe), 6.85 (s, 1 H, 5-H), 7.28 (s, 1 H, 8-H),
7.71–7.95 (m, 5 H, Ph), 8.16 (s, 1 H, 2Ј-H), 8.17 (s, 1 H, 4Ј-H)
ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 21.6 (Me), 25.4 (C-4),
39.8 (MeSO3), 49.0 (C-3), 56.2 (OMe), 56.2 (OMe), 106.1 (C-1Ј),
110.8 (C-5), 113.3 (C-8), 116.3 (CN), 117.1 (C-9), 126.1 (C-3Ј),
129.1 (Ph), 129.3 (Ph), 131.7 (Ph), 133.7 (C-10), 134.1 (Ph), 147.5
(C-7), 152.7 (C-4Ј), 154.1 (C-6), 158.7 (C-2Ј), 159.1 (C-1) ppm.
1-[1-Cyano-4-(4-methoxyphenyl)buta-1,3-dienyl]-6,7-dimethoxy-3,4-
dihydroisoquinolinium Mesylate (12e): Wine-red crystals, yield:
750 mg (1.52 mmol, 76 %). M.p. 91 °C (decomp.). 1H NMR
(CDCl3, 250 MHz): δ = 2.83 (s, 3 H, MeSO3), 3.06 (t, J = 7.7 Hz,
2 H, 4-H), 3.89 (s, 3 H, OMe), 3.98 (s, 3 H, OMe), 4.04 (s, 3 H,
OMe), 4.12 (t, J = 7.7 Hz, 2 H, 3-H), 6.87 (s, 1 H, 5-H), 6.96 (d, J
= 8.7 Hz, 2 H, C6H4OMe), 7.35 (dd, J1 = 14.8, J2 = 11.4 Hz, 1 H,
3Ј-H), 7.51 (s, 1 H, 8-H), 7.69 (d, J = 8.7 Hz, 2 H, C6H4OMe), 7.93
(d, J = 14. 8 Hz, 1 H, 4Ј-H), 8.74 (d, J = 11. 4 Hz, 1 H, 2Ј-H) ppm.
13C NMR (CDCl3, 62.5 MHz): δ = 26.1 (C-4), 39.0 (MeSO3), 42.2
(C-3), 55.9 (OMe), 56.4 (OMe), 56.9 (OMe), 99.1 (C-1Ј), 110.9 (C-
5), 113.7 (C-8), 114.0 (C6H4OMe), 117.5 (CN), 119.8 (C-9), 124.6
(C6H4OMe), 127.0 (C6H4OMe), 131.2 (C-3Ј), 132.2 (C-10), 147.8
(C-7), 148.0 (C-4Ј), 152.5 (C-6), 160.1 (C-2Ј), 163.0 (C6H4OMe),
166.0 (C-1) ppm.
1-[1-Cyano-4-(4-nitrophenyl)buta-1,3-dienyl]-6,7-dimethoxy-3,4-di-
hydroisoquinolinium Mesylate (12c): Yellow crystals, yield: 796 mg
(1.64 mmol, 82%). M.p. 93–95 °C (decomp.). 1H NMR (CDCl3,
250 MHz): δ = 2.82 (s, 3 H, MeSO3), 3.11 (t, J = 7.4 Hz, 2 H, 4-
H), 3.98 (t, J = 7.4 Hz, 2 H, 3-H), 4.05 (s, 3 H, OMe), 4.09 (s, 3
H, OMe), 6.90 (s, 1 H, 5-H), 7.43 (s, 1 H, 8-H), 7.52 (dd, J1 = 14.9,
J2 = 11.2 Hz, 1 H, 3Ј-H), 7.85 (d, J = 8.4 Hz, 2 H, C6H4NO2), 7.99
(d, J = 14.9 Hz, 1 H, 4Ј-H), 8.28 (d, J = 8.4 Hz, 2 H, C6H4NO2),
8.78 (d, J = 11.2 Hz, 1 H, 2Ј-H) ppm. 13C NMR (CDCl3,
62.5 MHz): δ = 25.4 (C-4), 39.1 (MeSO3), 41.3 (C-3), 56.2 (OMe),
56.6 (OMe), 103.1 (C-1Ј), 111.0 (C-5), 112.4 (C-8), 114.2 (CN),
115.7 (C-9), 124.0 (C-3Ј), 126.3 (C6H4NO2), 129.4 (C6H4NO2),
135.2 (C-10), 140.2 (C6H4NO2), 148.6 (C6H4NO2), 148.8 (C-7),
150.0 (C-4Ј), 157.4 (C-6), 159.2 (C-2Ј), 165.1 (C-1) ppm.
1-[1-Cyano-4-(4-methoxyphenyl)-3-methylbuta-1,3-dienyl]-6,7-di-
methoxy-3,4-dihydroisoquinolinium Mesylate (12f): Red crystals,
1
yield: 650 mg (1.34 mmol, 67%). M.p. 91 °C (decomp.). H NMR
(CDCl3, 250 MHz): δ = 2.44 (s, 3 H, CH3), 2.80 (s, 3 H, MeSO3),
3.05 (t, J = 7.6 Hz, 2 H, 4-H), 3.90 (s, 3 H, OMe), 3.98 (s, 3 H,
OMe), 4.07 (s, 3 H, OMe), 4.15 (t, J = 7.6 Hz, 2 H, 3-H), 6.91 (s,
1 H, 5-H), 6.95 (d, J = 8.7 Hz, 2 H, C6H4OMe), 7.51 (s, 1 H, 8-
H), 7.70 (d, J = 8.7 Hz, 2 H, C6H4OMe), 7.92 (s, 1 H, 4Ј-H), 8.43
(s, 1 H, 2Ј-H) ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 20.2 (Me),
26.2 (C-4), 39.0 (MeSO3), 42.2 (C-3), 55.9 (OMe), 56.3 (OMe), 56.8
(OMe), 104.1 (C-1Ј), 110.9 (C-5), 113.0 (C-8), 114.0 (C6H4OMe),
115.5 (CN), 120.2 (C-9), 124.6 (C6H4OMe), 127.0 (C6H4OMe),
128.4 (C-3Ј), 132.9 (C-10), 149.0 (C-7), 150.2 (C-4Ј), 152.5 (C-6),
162.5 (C-2Ј), 164.0 (C6H4OMe), 166.1 (C-1) ppm.
1-[1-Cyano-3-methyl-4-(4-nitrophenyl)buta-1,3-dienyl]-6,7-dimeth-
oxy-3,4-dihydroisoquinolinium Mesylate (12d): Yellow crystals,
yield: 650 mg (1.30 mmol, 65%). M.p. 143–144 °C (decomp.). 1H
NMR (CDCl3, 250 MHz): δ = 2.52 (s, 3 H, Me), 2.79 (s, 3 H,
MeSO3), 3.11 (t, J = 7.6 Hz, 2 H, 4-H), 3.90 (t, J = 7.6 Hz, 2 H,
3-H), 4.02 (s, 3 H, OMe), 4.04 (s, 3 H, OMe), 6.90 (s, 1 H, 5-H),
7.39 (s, 1 H, 8-H), 7.65 (d, J = 8.4 Hz, 2 H, C6H4NO2), 7.85 (s, 1
H, 4Ј-H), 8.26 (d, J = 8.4 Hz, 2 H, C6H4NO2), 8.41 (s, 1 H, 2Ј-H)
ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 21.6 (Me), 25.5 (C-4),
39.5 (MeSO3), 41.3 (C-3), 56.2 (OMe), 56.5 (OMe), 102.1 (C-1Ј),
111.2 (C-5), 112.4 (C-8), 114.0 (CN), 115.6 (C-9), 125.9 (C-3Ј),
126.0 (C6H4NO2), 130.0 (C6H4NO2), 135.2 (C-10), 140.2 General Procedure for the Synthesis of 6,7-Dihydro-4H-benzo[a]-
(C6H4NO2), 148.5 (C6H4NO2), 147.8 (C-7), 149.8 (C-4Ј), 157.3 (C-
6), 159.1 (C-2Ј), 165.4 (C-1) ppm.
quinolizines: TEA (2 mmol) was added to a solution of a 1-aza-
triene (12a–h, 1 mmol) in acetonitrile (10 mL). The solution
1098
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1092–1100

1,6-Electrocyclization of 1-Azatriene Derivatives
was stirred at room temp. or at reflux temperature (12b,d,f,h and
12a,c,e,g, respectively) for the required time (1–8 h). The solvent
was removed under reduced pressure, and the residue was dissolved
in CH2Cl2 (10 mL). The CH2Cl2 solution was washed with water
(2ϫ10 mL), dried (Na2SO4), and then concentrated under reduced
pressure to give the crude product, which was purified by column
chromatography on silica gel with hexane/EtOAc as eluent.
9,10-Dimethoxy-4-(4-methoxyphenyl)-6,7-dihydro-4H-benzo[a]quin-
olizine-1-carbonitrile (14e): Yellow crystals, yield: 258 mg
(0.69 mmol, 69%). M.p. 142 °C. 1H NMR (CDCl3, 250 MHz): δ =
2.55 (m, 1 H, 7-H), 2.81 (m, 1 H, 7-H), 2.98 (m, 1 H, 6-H), 3.20
(m, 1 H, 6-H), 3.80 (s, 3 H, OMe), 3.82 (s, 3 H, OMe), 3.90 (s, 3
H, OMe), 4.99 (d, J = 4.8 Hz, 1 H, 4-H), 5.11 (dd, J = 4.8, J =
9.6 Hz, 1 H, 3-H), 6.00 (d, J = 9.6 Hz, 1 H, 2-H), 6.54 (s, 1 H, 8-
H), 6.84 (d, J = 7.3 Hz, 2 H, C6H4OMe), 7.27 (d, J = 7.3 Hz, 2 H,
C6H4OMe), 7.91 (s, 1 H, 11-H) ppm. 13C NMR (CDCl3,
62.5 MHz): δ = 29.6 (C-7), 47.9 (C-6), 55.3 (OMe), 56.4 (OMe),
56.6 (OMe), 65.8 (C-4), 73.7 (C-1), 110.3 (C-8), 110.4 (C-3), 111.2
(C-11), 119.1 (C-12), 122.8 (C-2), 123.6 (CN), 124.7 (C6H4OMe),
128.6 (C6H4OMe), 129.7 (C6H4OMe), 132.9 (C-13), 147.5 (C-10),
148.8 (C-9), 150.6 (C-14), 160.1 (C6H4OMe) ppm. C23H22N2O3
(374.43): calcd. C 73.78, H 5.92, N 7.48; found C 73.57, H 6.03, N
7.55.
9,10-Dimethoxy-4-phenyl-6,7-dihydro-4H-benzo[a]quinolizine-1-
carbonitrile (14a): Yellow crystals, yield: 292 mg (0.85 mmol, 85%).
M.p. 175 °C. 1H NMR (CDCl3, 250 MHz): δ = 2.68 (m, 1 H, 7-
H), 2.88 (m, 1 H, 7-H), 3.08 (m, 1 H, 6-H), 3.22 (m, 1 H, 6-H),
3.89 (s, 3 H, OMe), 3.98 (s, 3 H, OMe), 5.19 (d, J = 4.9 Hz, 1 H,
4-H), 5.27 (dd, J = 4.9, J = 9.8 Hz, 1 H, 3-H), 6.15 (d, J = 9.8 Hz,
1 H, 2-H), 6.62 (s, 1 H, 8-H), 7.31–7.38 (m, 5 H, Ph), 7.94 (s, 1 H,
11-H) ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 29.3 (C-7), 47.1
(C-6), 56.0 (OMe), 56.3 (OMe), 66.1 (C-4), 73.3 (C-1), 110.0 (C-8)
111.0 (C-11), 114.5 (C-3), 121.0 (C-12), 123.0 (C-2), 124.1 (CN),
126.5 (Ph), 128.5 (Ph), 129.0 (Ph), 129.6 (C-13), 142.0 (Ph), 147.3
(C-10), 150.7 (C-9), 150.9 (C-14) ppm. C22H20N2O2 (344.41): calcd.
C 76.72, H 5.85, N 8.13; found C 76.40, H 5.51, N 8.03.
9,10-Dimethoxy-4-(4-methoxyphenyl)-3-methyl-6,7-dihydro-4H-
benzo[a]quinolizine-1-carbonitrile (14f): Yellow crystals, yield:
252 mg (0.65 mmol, 65 %). M.p. 127 °C. 1H NMR (CDCl3, 250
MHz): δ = 1.60 (s, 3 H, Me), 2.59 (m, 1 H, 7-H), 2.82 (m, 1 H, 7-
H), 3.00 (m, 1 H, 6-H), 3.20 (m, 1 H, 6-H), 3.76 (s, 3 H, OMe),
3.86 (s, 3 H, OMe), 3.95 (s, 3 H, OMe), 4.79 (s, 1 H, 4-H), 5.92 (s,
1 H, 2-H), 6.59 (s, 1 H, 8-H), 6.82 (d, J = 7.3 Hz, 2 H, C6H4OMe),
9,10-Dimethoxy-3-methyl-4-phenyl-6,7-dihydro-4H-benzo[a]quinol-
izine-1-carbonitrile (14b): Yellow crystals, yield: 294 mg (0.82 mmol,
82%). M.p. 176 °C. 1H NMR (CDCl3, 250 MHz): δ = 1.42 (s, 3 H,
Me), 2.69 (m, 1 H, 7-H), 2.83 (m, 1 H, 7-H), 2.98 (m, 1 H, 6-H),
3.20 (m, 1 H, 6-H), 3.83 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 4.67
(s, 1 H, 4-H), 5.75 (s, 1 H, 2-H), 6.40 (s, 1 H, 8-H), 7.11–7.16 (m,
5 H, Ph), 7.73 (s, 1 H, 11-H) ppm. 13C NMR (CDCl3, 62.5 MHz):
δ = 20.3 (Me), 29.7 (C-7), 47.4 (C-6), 56.3 (OMe), 56.6 (OMe), 70.7
(C-4), 73.9 (C-1), 110.3 (C-8), 111.2 (C-11), 119.2 (C-12), 121.4 (C-
2), 123.6 (CN), 124.7 (Ph), 127.5 (Ph), 129.0 (Ph), 129.2 (C-13),
129.7 (C-3), 140.7 (Ph), 147.6 (C-10), 149.0 (C-9), 150.7 (C-14)
ppm. C23H22N2O2 (358.43): calcd. C 77.07, H 6.19, N 7.82; found
C 76.99, H 6.34, N 7.71.
7.27 (d, J = 7.3 Hz, 2 H, C6H4OMe), 7.90 (s, 1 H, 11-H) ppm. 13
C
NMR (CDCl3, 62.5 MHz): δ = 20.3 (Me), 29.7 (C-7), 47.2 (C-6),
55.6 (OMe), 56.3 (OMe), 56.6 (OMe), 70.0 (C-4), 73.8 (C-1), 110.3
(C-8), 111.2 (C-11), 114.5 (C-3), 119.1 (C-12), 121.5 (C-2), 123.7
(CN), 124.8 (C6H4OMe), 128.6 (C6H4OMe), 129.7 (C6H4OMe),
132.9 (C-13), 147.6 (C-10), 148.8 (C-9), 150.7 (C-14), 160.2
(C6H4OMe) ppm. C24H24N2O3 (388.46): calcd. C 74.21, H 6.23, N
7.21; found C 74.09, H 6.19, N 7.20.
4-[4-(Dimethylamino)phenyl]-9,10-dimethoxy-6,7-dihydro-4H-benzo-
[a]quinolizine-1-carbonitrile (14g): Yield: 345 mg (0.89 mmol, 89%).
M.p. 153 °C. 1H NMR (CDCl3, 250 MHz): δ = 2.70 (m, 1 H, 7-
H), 2.75 (m, 1 H, 7-H), 2.84 (s, 6 H, NMe2) 2.97 (m, 1 H, 6-H),
3.09 (m, 1 H, 6-H), 3.78 (s, 3 H, OMe), 3.87 (s, 3 H, OMe), 4.95
(d, J = 4.8 Hz, 1 H, 4-H), 5.13 (dd, J = 4.8, J = 9.7 Hz, 1 H, 3-H),
6.02 (d, J = 9.7 Hz, 1 H, 2-H), 6.51 (s, 1 H, 8-H), 6.59 (d, J =
8.6 Hz, 2 H, C6H4NMe2), 7.16 (d, J = 8.6 Hz, 2 H, C6H4NMe2),
7.82 (s, 1 H, 11-H) ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 29.7
(C-7), 40.8 (NMe2), 47.2 (C-6), 56.4 (OMe), 56.6 (OMe), 65.8 (C-
4), 73.1 (C-1), 110.3 (C-8), 111.4 (C-11), 112.8 (Ph-NMe2), 115.3
(C-12), 121.5 (C-2), 122.9 (CN), 124.9 (C-3), 128.0 (C6H4NMe2),
128.1 (C6H4NMe2), 130.1 (C-13), 147.5 (C-10), 150.9 (C-9), 151.0
(C6H4NMe2), 151.0 (C-14) ppm. C24H25N3O2 (387.47): calcd. C
74.39, H 6.50, N 10.84; found C 74.30, H 6.60, N 10.82.
9,10-Dimethoxy-4-(4-nitrophenyl)-6,7-dihydro-4H-benzo[a]quinol-
izine-1-carbonitrile (14c): Yellow crystals, yield: 292 mg (0.75 mmol,
1
75%). M.p. 197 °C. H NMR (CDCl3, 250 MHz): δ = 2.68 (m, 1
H, 7-H), 2.88 (m, 1 H, 7-H), 3.08 (m, 1 H, 6-H), 3.22 (m, 1 H, 6-
H), 3.89 (s, 3 H, OMe), 3.98 (s, 3 H, OMe), 5.16 (d, J = 5.0 Hz, 1
H, 4-H), 5.25 (dd, J = 5.0, J = 9.3 Hz, 1 H, 3-H), 6.11 (d, J =
9.3 Hz, 1 H, 2-H), 6.57 (s, 1 H, 8-H), 7.45 (d, J = 8.7 Hz, 2 H,
C6H4NO2), 7.83 (s, 1 H, 11-H), 8.13 (d, J = 8.7 Hz, 2 H, C6H4NO2)
ppm. 13C NMR (CDCl3, 62.5 MHz): δ = 28.2 (C-7), 46.6 (C-6),
55.0 (OMe), 55.3 (OMe), 64.2 (C-4), 73.0 (C-1), 109.0 (C-8), 109.8
(C-11), 112.1 (C-3), 122.3 (C-12), 123.1 (C-2), 123.2 (CN), 123.4
(C6H4NO2), 126.2 (C6H4NO2), 127.5 (C6H4NO2), 128.4 (C-13),
146.4 (C6H4NO2), 146.9 (C-10), 147.1 (C-9), 149.9 (C-14) ppm.
C22H19N3O4 (389.40): calcd. C 67.86, H 4.92, N 10.79; found C
67.65, H 4.86, N 10.88.
4-[4-(Dimethylamino)phenyl]-9,10-dimethoxy-3-methyl-6,7-dihydro-
9,10-Dimethoxy-3-methyl-4-(4-nitrophenyl)-6,7-dihydro-4H-benzo-
[a]quinolizine-1-carbonitrile (14d): Yellow crystals, yield: 290 mg
(0.72 mmol, 72%). M.p. 160 °C. 1H NMR (CDCl3, 250 MHz): δ =
1.57 (s, 3 H, Me), 2.63 (m, 1 H, 7-H), 2.81 (m, 1 H, 7-H), 2.99 (m,
4H-benzo[a]quinolizine-1-carbonitrile
(14h):
Yield:
329 mg
(0.82 mmol, 82%). M.p. 155 °C. 1H NMR (CDCl3, 250 MHz): δ =
1.55 (s, 3 H, Me) 2.59 (m, 1 H, 7-H), 2.85 (s, 6 H, NMe2), 2.95 (m,
1 H, 7-H), 3.10 (m, 1 H, 6-H), 3.63 (m, 1 H, 6-H), 3.86 (s, 3 H,
1 H, 6-H), 3.17 (m, 1 H, 6-H), 3.81 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 4.67 (s, 1 H, 4-H), 5.86 (s, 1 H, 2-H),
OMe), 4.93 (s, 1 H, 4-H), 5.92 (s, 1 H, 2-H), 6.54 (s, 1 H, 8-H), 6.52 (s, 1 H, 8-H), 6.59 (d, J = 8.5 Hz, 2 H, C6H4NMe2), 7.16 (d,
7.47 (d, J = 8.5 Hz, 2 H, C6H4NO2), 7.84 (s, 1 H, 11-H), 8.13 (d, J = 8.5 Hz, 2 H, C6H4NMe2), 7.84 (s, 1 H, 11-H) ppm. 13C NMR
J = 8.5 Hz, 2 H, C6H4NO2) ppm. 13C NMR (CDCl3, 62.5 MHz): (CDCl3, 62.5 MHz): δ = 20.4 (Me), 29.7 (C-7), 40.8 (NMe2), 47.2
δ = 20.3 (Me), 29.6 (C-7), 47.7 (C-6), 56.4 (OMe), 56.6 (OMe), 70.0
(C-4), 74.6 (C-1), 108.9 (C-8) 110.4 (C-11), 111.1 (C-3), 120.4 (C-
12), 120.9 (C-2), 122.4 (CN), 124.0 (C6H4NO2), 124.6 (C6H4NO2),
(C-6), 56.3 (OMe), 56.6 (OMe), 70.1 (C-4), 73.7 (C-1), 110.3 (C-8)
111.2 (C-11), 112.6 (C6H4NMe2), 118.8 (C-12), 121.7 (C-2), 123.9
(CN), 125.0 (C-3), 128.4 (C6H4NMe2), 128.6 (C6H4NMe2), 129.7
128.2 (C6H4NO2), 129.5 (C-13), 147.1 (C6H4NO2), 147.8 (C-10), (C-13), 147.6 (C-10), 149.7 (C-9), 150.6 (C6H4NMe2), 150.6 (C-14)
148.9 (C-9), 151.0 (C-14) ppm. C23H21N3O4 (403.43): calcd. C ppm. C25H27N3O2 (401.50): calcd. C 74.79, H 6.78, N 10.47; found
68.47, H 5.25, N 10.42; found C 68.59, H 5.19, N 10.40.
C 74.83, H 6.77, N 10.55.
Eur. J. Org. Chem. 2008, 1092–1100
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1099

Z. Vincze, Z. Mucsi, P. Scheiber, P. Nemes
FULL PAPER
Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson,
P. Y. Ayala, Q. Cui, K. Morokuma, D. K. Malick, A. D.
Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V.
Ortiz, A. G. Baboul, B. B. Stefanov, G. Liu, A. Liashenko, P.
Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J. Fox,
T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M.
Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, J. L. Andres, C. Gonzalez, M. Head–Gordon, E. S. Re-
plogle, J. A. Pople, Gaussian 03, revision 6.0, Gaussian, Inc.,
Pittsburgh, PA, 2003..
Supporting Information (see footnote on the first page of this arti-
cle): Electronic total energies of all computed species, additional
data for the ring-strain estimation for 17a.
Acknowledgments
The authors are grateful to Dr. Sándor Boros for the NMR mea-
surements and to Mrs. Vali Sz. Marjai for her technical help.
[9] S. Boros, G. Tóth, A Practical Comparison of Methods for De-
n
termination of Long-range JC,H Coupling constants, VIth Cen-
[1] a) S.-U. Saraf, Heterocycles 1981, 16, 803–841; b) F. D. Popp,
R. F. Watts, Heterocycles 1977, 6, 1189–1228; c) Z. Vincze,
A. B. Bíró, M. Csékei, G. Timári, A. Kotschy, Synthesis 2006,
8, 1375–1385.
[2] a) A. Roy, S. Nandi, H. Ila, H. Junjappa, Org. Lett. 2001, 3,
229–232; b) S. Chakrabarti, M. C. Srivastava, H. Ila, H. Jun-
jappa, Synlett 2003, 2369–2373.
[3] A. W. Erian, Chem. Rev. 1993, 93, 1991–2005.
[4] P. Nemes, B. Balázs, G. Tóth, P. Scheiber, Synlett 1999, 222–
224.
[5] P. Nemes, Z. Vincze, B. Balázs, G. Tóth, P. Scheiber, Synlett
2003, 250–252.
[6] Z. Vincze, P. Nemes, B. Balázs, G. Tóth, P. Scheiber, Synlett
2004, 1023–1026.
[7] a) P. J. Stephens, F. J. Devlin, C. F. Chabalowski, M. J. Frisch,
J. Phys. Chem. 1994, 98, 11623–11627; b) A. D. Beke, J. Chem.
Phys. 1993, 98, 5648–5651.
[8] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Mont-
gomery, R. E. Stratmann Jr, J. C. Burant, S. Dapprich, J. M.
Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas,
J. Tomasi, V. Barone, M. Cossi, R. Cammi, B. Mennucci, C.
tral European NMR Symposium and Bruker Users Meeting,
Linz, Austria, September 27–28, 2004.
[10] U. Vogeli, W. von Philipsborn, Org. Magn. Reson. 1975, 7, 617–
627.
[11] D. F. Maynard, W. H. Okamura, J. Org. Chem. 1995, 60, 1763–
1771.
[12] F. Markwardt, W. Barthel, G. Faust, W. Fiedler, A. Hoffmann,
Acta Biol. Med. Germ. 1969, 23, 295–306.
[13] T. P. M. Coumans, A. W. Ehlers, K. Lammertsma, E.-U.
Würthwein, S. Grimme, Chem. Eur. J. 2004, 10, 6468.
[14] T. A. Rokob, A. Hamza, I. Pápai, Org. Lett. 2007, 9, 4279.
[15] P. v. R. J. Schleyer, C. Maerker, A. Dransfeld, H. Jiao,
N. J. R. v. E. Hommes, J. Am. Chem. Soc. 1999, 121, 6737.
[16] H. Jiao, P. v. R. Schleyer, J. Phys. Org. Chem. 1998, 11, 655–
662.
[17] K. Tanaka, H. Mori, M. Yamamoto, S. Katsumura, J. Org.
Chem. 2001, 66, 3099–3110.
[18] P. v. R. J. Schleyer, C. Maerker, A. Dransfeld, H. Jiao,
N. J. R. v. E. Hommes, J. Am. Chem. Soc. 1999, 121, 6737.
Received: September 26, 2007
Published Online: January 3, 2008
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