An investigation of the scope of the 1,7-electrocyclization of α,β:γ,δ-conjugated azomethine ylides

Article abstract of DOI:10.1016/j.tet.2014.03.078

Substituents on the diene component have little influence on the periselectivity of the cyclizations of α,β:γ,δ-conjugated azomethine ylides, with 1,7-electrocyclizations predominating. In some cases, subtle changes to these substituents can, however, influence the product formed, through their effect on the relative energies of the transition states for the 1,5- (6π) and 1,7-electrocyclization (8π) processes. The most striking changes in periselectivity occur for phenylethenyl-substituted azomethine ylides 3d-f, which can give either a pyrroline 4d,f or dihydrobenzazepine 6e, depending upon the alkene configuration.

Full text of DOI:10.1016/j.tet.2014.03.078

Tetrahedron 70 (2014) 3621e3629
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An investigation of the scope of the 1,7-electrocyclization
of a,b:g,d-conjugated azomethine ylides
,
y
b
b
c
Weimin Zhang a, Fuqiang Ning a , Linda Varadi , David E. Hibbs , James A. Platts ,
ꢀ
d
a
a,b,
*
ꢀ
Miklos Nyerges , Rosaleen J. Anderson , Paul W. Groundwater
a Sunderland Pharmacy School, The Sciences Complex, University of Sunderland, Sunderland SR1 3SD, UK
b Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia
c School of Chemistry, Cardiff University, Cardiff CF10 3AT, UK
d
ꢀ
Servier Research Institute of Medicinal Chemistry, 1131 Budapest Zahony u. 7, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Substituents on the diene component have little influence on the periselectivity of the cyclizations of
-conjugated azomethine ylides, with 1,7-electrocyclizations predominating. In some cases, subtle
changes to these substituents can, however, influence the product formed, through their effect on the
relative energies of the transition states for the 1,5- (6 ) and 1,7-electrocyclization (8 ) processes. The
most striking changes in periselectivity occur for phenylethenyl-substituted azomethine ylides 3def,
Received 30 January 2014
Received in revised form 11 March 2014
Accepted 24 March 2014
Available online 12 April 2014
a,b:g,d
p
p
which can give either
configuration.
a
pyrroline 4d,f or dihydrobenzazepine 6e, depending upon the alkene
Keywords:
Azomethine ylides
1,5-Electrocyclization
1,7-Electrocyclization
PyrrolinesA azepines
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
pyrrolines 4aec via a 1,5-electrocyclization, Scheme 2 (pyrrole 5
was obtained as a minor product of the cyclization of azomethine
ylide 3a). Isomerization of the double bond, from (E)-3c to (Z)-3c0,
and subsequent 1,7-electrocyclization onto the aryl ring, was only
observed for the 4-chloro derivative 3c, from which a minor
amount of the dihydrobenzazepine 6c was also obtained.
Azomethine ylides, e.g., 3, Scheme 1, can be used in the prepa-
ration of a range of heterocycles through 1,3-dipolar cycloaddi-
tions,1 1,5-electrocyclizations,2 or 1,7-electrocyclizations,3,4 and
routes to these versatile intermediates include the decarboxylation
of iminium salts,5 the ring-opening of aziridines,6 and the 1,2-
The 1,7-electrocyclization of the azomethine ylide 3e, in which
prototropy of
studies on these allyl anion type 1,3-dipoles, we describe here an
investigation of the scope of the 1,7-electocyclization of
a
-imino esters.7 In continuation of our previous
the configuration of the
dihydrobenzazepine 6e. Intriguingly, the azomethine ylides 3d,f in
which only the configuration of the -phenylethenyl substituent
b-phenylethenyl group is (Z), gave the
a,
b:g
,d-
b
conjugated azomethine ylides 3. In all cases, the azomethine ylides
3 in this study were generated by the decarboxylation of an imi-
nium salt 2 formed by the condensation of an aldehyde 1 and
sarcosine (N-methylglycine), Scheme 1.
has changed, to (E), were found to undergo 1,5-electrocyclization,
giving the pyrrolines 4d,f in good to excellent yield, Scheme 3.
As can be seen from Fig. 1, the (E)-configuration of the phenyl-
ethenyl substituent results in a greatly reduced separation between
the methylene terminus of the azomethine ylide 3d and the qua-
ternary carbon to which it cyclizes in a 1,5-electocyclization (6p),
resulting in a dramatically lower energy barrier for this process and
2. Results and discussion
a change in the periselectivity, to give the pyrroline product 4d of
Generation of the (E)-azomethine ylides 3aec, from the corre-
sponding aldehydes 1aec, led to the expected formation of the
a
1,5-electrocyclization. Molecular modelling of this process,
Table 1 and Fig. 2, confirms the similar energy barriers for the 1,7-
electrocyclizations of both dipoles (3d and 3e), Fig. 2 (blue); the
increased energy barrier for the 1,5-electrocyclization for the (Z)-
alkenyl substituted dipole 3e, Fig. 2b (red), resulting in a 1,7-
electrocyclization for this reactive intermediate (to give benzaze-
pine 6e); and the lower energy barrier for the 1,5-electrocyclization
* Corresponding author. Current address: Faculty of Pharmacy, Pharmacy and
Bank Building, University of Sydney, Camperdown Campus, Sydney, NSW 2006,
Australia. Tel.: þ61 (0)2 9114 1232; fax: þ61 (0)2 9351 4391; e-mail address: paul.
groundwater@sydney.edu.au (P.W. Groundwater).
y
The late.
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.03.078

3622
W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
Scheme 1.
Scheme 2.
of the (E)-alkenyl substituted dipole 3d, Fig. 2a (red), resulting in
a 1,5-electrocyclization (to give pyrroline 4d).
ylides in which this bond is aromatic 3n-u (to give the dihydro[2]
benzazepines 6neu), Scheme 7. The intermediacy of azomethine
ylides in these processes was shown by the trapping of azomethine
ylide 3o (R¼Ph) with N-phenylmaleimide to give a single di-
astereoisomer of the cycloadduct 12, Scheme 8, with the relative
stereochemistry being confirmed by the observation of a NOE be-
tween H-2a and H-3.
Generation of azomethine ylide 3g (from aldehyde 1g) again led
to the formation of the benzazepine 6g, while the bromo derivative
3h (from 1h) gave a mixture of the benzazepine 6h and the pyrrole
11 (formed by a 1,5-electrocyclization to the bromopyrroline fol-
lowed by dehydrobromination), Scheme 4.
The azomethine ylides 3iel underwent 1,7-electrocyclization to
the dihydroazepines 6iel, with no evidence for the formation of the
pyrroline products of a 1,5-electrocyclization, Scheme 5. The azo-
methine ylide in which the a,b-bond is the 2,3-position of a thio-
phene ring 3m also underwent a 1,7-electrocyclization, to give the
dihydrothieno[3,2-c]azepine 6m, Scheme 6, as did the azomethine
For the azomethine ylide 3v (containing a (Z)-alkene sub-
stituent), no electrocyclization was observed, Scheme 9, while the
corresponding (E)-alkenyl substituted azomethine ylide 3o gave
the dihydro[2]benzazepine 6o in good yield. The 1,7-
electrocyclization of azomethine ylide 3v is presumably blocked
by the bulky cis-phenyl group and more rigid unsaturated system

W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
3623
Scheme 3.
compared to that of 3o. This blocking effect can be accounted for by
3. Experimental
the transition state geometry for a 1,7-electrocyclization, resulting
in a steric clash between the phenyl group and the nitrogen of the
azomethine ylide, as shown in Fig. 3.8
3.1. General experimental conditions
Finally, the electrocyclization of the thiophene analogue 3w in-
volves the disruption of two aromatic rings but the g,d-bond, which
forms part of the thiophene ring, possesses a reasonable amount of
double bond character and the cyclization gives the expected thieno
[2,3-d][2]benzazepine 6w in good yield, Scheme 10.
Melting points were determined on a Reichert hot-stage appa-
ratus and are uncorrected. Elemental analyses were performed on
a PerkineElmer 240C or Carlo Erba 1106 Elemental Analyser.
IR spectra were recorded on a Unicam research series FTIR
spectrophotometer using KBr discs or liquid films. 1H NMR spectra
were acquired on a JEOL JNM-GSX 270 FT NMR at 270 MHz, or
Bruker AVANCE 300 at 300 MHz. Coupling constants are given in Hz
and all chemical shifts are relative to an internal standard of tet-
ramethylsilane. 13C NMR spectra were obtained on the JEOL JNM-
GFX 270 FT NMR (67.5 MHz) spectrometer and Bruker AVANCE
300 (75 MHz). Low resolution electron impact mass spectra were
In conclusion, the 1,7-electrocyclization of
a,b:g,d-conjugated
azomethine ylides tolerates a wide range of substituents in the
diene component. The nature of the substituents can, in some
cases, influence the electrocyclization products obtained, with even
very subtle changes having significant effects on the energy bar-
riers for 1,5- versus 1,7-electrocyclizations.

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W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
Fig. 1. Calculated transition state 7 distances between the reacting termini for the 1,5-electrocyclization of (a) (E)-20-phenylethenyl 3d and (b) (Z)-20-phenylethenyl-substituted
azomethine ylides 3e.
obtained on a Trio 2000 VG. High resolution spectra were obtained
on a VG ZAB-E spectrometer (E.P.S.R.C. Mass Spectrometry Service
Centre, Swansea) or Bruker APEX II FT mass spectrometer.
Table 1
Thin layer chromatography was performed on Merck silica gel
60F254. Organic solvents were dried using anhydrous magnesium
sulfate and anhydrous sodium sulfate unless otherwise stated. All
solvents were purified according to standard procedures. Diethyl
ether and tetrahydrofuran were freshly distilled over sodium wire
with a trace of benzophenone. Toluene was distilled from, and
stored over, sodium wire. Fluka silica gel 60 (230e400 mesh) was
used for wet flash chromatography. The samples were applied in
liquid form or were pre-adsorbed onto silica 60 (230e400 mesh)
from dichloromethane solutions.
Relative free energies (B3LYP/6-31G* [kJ molꢀ1]) for the transition states, in-
termediates and products of the 1,5- and 1,7-electrocyclizations of dipoles 3e and 3d
Reactant
1,5
1,7
TS 7
Product 4 TS1 8 Intermediate 9 TS2 10 Product 6
3d (E)
3e (Z)
0
0
24.8
120.0 ꢀ113.8
ꢀ130.0
61.1
66.7
ꢀ48.1
ꢀ51.6
40.9
34.9
ꢀ132.0
ꢀ138.7
(a)
(b)
Fig. 2. Reaction profiles for 1,5- (red) and 1,7-electrocyclizations (blue) of; (a) (E)-20-phenylethenyl 3d and (b) (Z)-20-phenylethenyl 3e substituted azomethine ylides.

W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
3625
Scheme 4.
Scheme 5.
Scheme 6.
Scheme 7.
3.2. Generation and reaction of azomethine ylides
under dry nitrogen, for 12 h. After cooling, the mixture was filtered
to remove any solid and the solvent was evaporated under reduced
pressure. The residue was purified using column chromatography
on silica to give the products.
ꢁ
A mixture of the aldehyde, sarcosine, and 4 A molecular sieves
(2 g) in anhydrous tetrahydrofuran or toluene was heated at reflux,

3626
W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
d
ppm 36.8 (NCH3), 121.7 (quat) 122.7 (CH), 122.8 (CH), 124.1 (2ꢂ
CH), 124.5 (quat), 126.7 (CH) 128.4 (2ꢂ CH), 128.8 (2ꢂ CH), 129.1
(2ꢂ CH), 135.5 (quat), 143.5 (quat), 145.8 (quat).
3.2.2. 2,3-Dihydro-1-methyl-3-(3-nitrophenyl)-4-phenyl-1H-pyrrole
4b. This was prepared, as above, from (E)-3-(3-nitrophenyl)-2-
phenylpropenal 1b (0.51 g, 2 mmol), sarcosine (0.3 g, 3.3 mmol)
in toluene (20 mL), to give 2,3-dihydro-1-methyl-3-(3-
nitrophenyl)-4-phenyl-1H-pyrrole 4b as a brown oil (0.24 g, 43%);
(found: MHþ, 281.128. Calcd for C17H17N2O2: MHþ, 281.128); nmax
(liquid film)/cmꢀ1 1608 (C]C), 1525 (NO2), 1346 (NO2); 1H NMR
Scheme 8.
(270 MHz, CDCl3)
d
ppm 2.63 (3H, s, NCH3), 3.12 (1H, dd, J¼9.9 and
3.9 Hz, H-2a), 3.42 (1H, t, J¼9.9 Hz, H-2b), 4.35 (1H, dd, J¼9.9 and
3.9 Hz, H-3), 6.64 (1H, s, ]CH, H-5), 6.87e8.10 (9H, m, AreH); 13
C
NMR (67.5 MHz, CDCl3)
d ppm 39.9 (CH3), 49.6 (CH), 64.5 (CH2),
117.5 (quat), 122.1 (CH), 123.0 (CH), 123.9 (2ꢂ CH), 124.9 (CH), 128.8
(2ꢂ CH), 129.9 (CH), 1134.2 (CH), 135.3 (quat), 140.9 (CH), 1146.7
(quat), 149.1 (quat).
Scheme 9.
3.2.3. 3-(4-Chlorophenyl)-2,3-dihydro-1-methyl-4-phenyl-1H-pyr-
role 4c and 8-chloro-2,3-dihydro-2-methyl-4-phenyl-1H-2-
benzazepine
6c. (E)-3-(4-Chlorophenyl)-2-phenylpropenal
1c
(0.7 g, 2.9 mmol) was reacted with sarcosine (0.4 g, 4.4 mmol) in
toluene (20 mL) as described above. Removal of the solid, by fil-
tration, and the solvent by evaporation under reduced pressure,
gave a residue, which was separated by column chromatography on
silica, eluting with petroleum ether (60e80 ꢁC)/ether (75:25) to
give 3-(4-chlorophenyl)-2,3-dihydro-1-methyl-4-phenyl-1H-pyr-
role 4c as a yellow oil (0.51 g, 65%); (found: MHþ, 270.105. Calcd for
Fig. 3. Transition state geometry for the 1,7-electrocyclization of azomethine ylide 3v.
C
17H1735ClN : MHþ, 270.104); nmax (liquid film)/cmꢀ1 1609 (C]C),
Scheme 10.
3.2.1. 2,3-Dihydro-1-methyl-3-(4-nitrophenyl)-4-phenyl-1H-pyrrole
1487 (C]C); 1H NMR (270 MHz, CDCl3)
d ppm 2.72 (3H, s, NCH3),
4a and 1-methyl-3-(4-nitrophenyl)-4-phenylpyrrole 5. The reaction
between (E)-3-(4-nitrophenyl)-2-phenylpropenal 1a (0.51 g,
2 mmol) and sarcosine (0.3 g, 3.3 mmol) in toluene (20 mL), was
carried out as described above. The solid was removed by filtration
and the solvent was evaporated under reduced pressure. Flash
chromatography of the residue on silica, eluting with hexane/ethyl
acetate (75:25) gave 2,3-dihydro-1-methyl-3-(4-nitrophenyl)-4-
phenyl-1H-pyrrole 4a as red needle-like crystals (0.23 g, 41%), mp
102e104 ꢁC; (Found: C, 72.75; H, 5.8; N, 9.9. C17H16N2O2 requires: C,
72.8; H, 5.75; N, 10.0) (Found: MHþ, 281.128. Calcd for C17H17N2O2:
MHþ, 281.128); nmax (KBr)/cmꢀ1 1594 (C]C), 1507 (NO2), 1341
3.16 (1H, dd, J¼9.6 and 4.8 Hz, Ha-2), 3.54 (1H, dd, J¼9.9 and 9.6 Hz,
Hb-2), 4.46 (1H, ddd, J¼9.6, 4.8 and 0.9 Hz, H-3), 6.69 (1H, d,
J¼0.9 Hz, 5-H), 6.78e7.27 (9H, m, AreH); 13C NMR (67.5 MHz,
CDCl3)
d ppm 40.1 (CH3), 49.4 (CH), 64.9 (CH2), 117.9 (quat), 124.0
(2ꢂ CH), 124.7 (CH), 128.7 (2ꢂ CH), 129.1 (2ꢂ CH), 129.4 (2ꢂ CH),
132.5 (quat), 135.8 (quat), 140.4 (CH), 143.0 (quat); and 8-chloro-
2,3-dihydro-2-methyl-4-phenyl-1H-2-benzazepine 6c as a yellow
oil (40 mg, 5%); (found: MHþ, 270.105. Calcd for C17H1735ClN :
MHþ, 270.104); 1H NMR (270 MHz, CDCl3)
d
ppm 2.41 (3H, s, NCH3),
3.70 (2H, s), 3.75 (2H, s), 6.69 (1H, s, H-5), 7.10e7.40 (8H, m, AreH);
13C NMR (67.5 MHz, CDCl3)
ppm 43.2 (CH3), 60.3 (CH2), 60.9 (CH2),
d
(NO2); 1H NMR (270 MHz, CDCl3)
d
ppm 2.74 (3H, s, NCH3), 3.21 (1H,
126.8 (2ꢂ CH), 127.7 (CH), 128.1 (CH), 128.8 (CH), 128.9 (2ꢂ CH),
129.4 (CH), 132.3 (CH), 133.0 (quat), 135.8 (quat), 139.5 (quat), 142.2
(quat), 142.7 (quat).
dd, J¼9.9 and 4.5 Hz, H-2a), 3.54 (1H, t, J¼9.9 Hz, H-2b), 4.46 (1H, dd,
J¼9.9 and 4.5 Hz, H-3), 6.73 (1H, s, H-5), 7.00e7.04 (5H, m), 7.12 (2H,
d, J¼9.0 Hz), 7.40 (2H, d, J¼9.0 Hz); 13C NMR (67.5 MHz, CDCl3)
d
ppm 40.0 (CH3), 49.8 (CH), 64.4 (CH2), 117.6 (quat), 123.9 (2ꢂ CH),
3.2.4. (10E)-2,3-Dihydro-1,4-dimethyl-3-phenyl-3-(20-phenyl-
ethenyl)-1H-pyrrole 4d. The reaction between a mixture of (2Z,4E)-
and (2Z,4Z)-2-methyl-3,5-diphenylpenta-2,4-dienal 1d and 1e (3:1,
0.50 g, 2.02 mmol), and sarcosine (0.36 g, 4.04 mmol) was carried
out in toluene (50 mL) for 16 h, as described above. The solid was
removed by filtration and the solvent was evaporated under re-
duced pressure. Flash chromatography of the residue on silica,
eluting with hexane/ethyl acetate (90:10 to 70:30), gave (E)-2,3-
dihydro-1,4-dimethyl-3-phenyl-3-(20-phenylethenyl)-1H-pyrrole
124.4 (2ꢂ CH), 125.0 (2ꢂ CH), 128.8 (2ꢂ CH), 130.0 (CH), 135.3
(quat), 140.7 (CH), 147.3 (quat), 152.3 (quat); and 1-methyl-3-
(4-nitrophenyl)-4-phenylpyrrole 5 as a brown oil (90 mg, 16%);
(found: MHþ, 279.113. Calcd for C17H15N2O2: MHþ, 279.113); nmax
(liquid film)/cmꢀ1 1594 (C]C), 1513 (NO2), 1348 (NO2); 1H NMR
(270 MHz, CDCl3)
d
ppm 3.65 (3H, s, NCH3), 6.64 (1H, d, J¼2.4 Hz, ]
CH), 6.77 (1H, d, J¼2.4 Hz, ]CH), 7.12e7.18 (5H, m, AreH), 7.25 (2H,
d, J¼9.0 Hz), 7.97 (2H, d, J¼9.0 Hz); 13C NMR (67.5 MHz, CDCl3)

W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
3627
4d as a pale yellow oil (0.28 g, 51%); (found: MHþ, 276.175. Calcd for
20H22N: MHþ, 276.175); nmax (liquid film)/cmꢀ1 1599 (C]C), 1493
CH), 129.6 (CH), 130.0 (CH), 130.9 (CH), 137.4 (quat), 137.5 (quat),
141.3 (quat), 142.9 (quat).
C
(C]C); 1H NMR (270 MHz, CDCl3)
d
ppm 1.62 (3H, d, J¼1.3 Hz, CH3),
2.54 (3H, s, NCH3), 3.12 (1H, d, J¼9.9 Hz, H-2a), 3.43 (1H, d, J¼9.9 Hz,
H-2b), 5.78 (1H, q, J¼1.3 Hz, ]CH, H-5), 6.48 (1H, d, J¼16.5 Hz, ]
CH), 6.58 (1H, d, J¼16.5 Hz, ]CH), 7.18e7.49 (10H, m, AreH); 13C
3.2.8. 5-Bromo-2,3-dihydro-2-methyl-4-phenyl-1H-2-benzazepine
6h
and
1-methyl-3,4-diphenylpyrrole
11. (E)-3-Bromo-2,3-
diphenyl-2-propenal 1h (0.4 g, 1.4 mmol) was reacted with sarco-
sine (0.25 g, 2.8 mmol) as described above. The solid was removed
by filtration and the solvent by evaporation under reduced pressure
and the residue was separated by column chromatography on silica,
eluting with hexane/ethyl acetate (75 : 25) to give 1-methyl-3,4-
diphenylpyrrole 11 (0.25 g, 77%), mp 122e124 ꢁC (lit.9
124e126 ꢁC); (Found: C, 87.5; H, 6.5; N, 5.9. C17H15N requires: C,
87.5; H, 6.48; N, 6.0) (found: MHþ, 234.129. Calcd for C17H16N: MHþ,
234.128); nmax (KBr)/cmꢀ1 1539 (C]C), 1483 (C]C); 1H NMR
NMR (67.5 MHz, CDCl3)
d ppm 10.6 (CH3), 41.1 (NCH3), 59.6 (quat),
69.7 (CH2), 116.6 (quat), 126.26 (CH), 126.31 (2ꢂ CH), 127.1 (CH),
127.70 (2ꢂ CH), 128.3 (2ꢂ CH), 128.5 (2ꢂ CH), 128.9 (CH), 133.1
(CH), 137.6 (quat), 138.6 (CH), 145.2 (quat).
3.2.5. (10E)-2,3-Dihydro-1-methyl-3,4-diphenyl-3-(20-phenyl-
ethenyl)-1H-pyrrole 4f. The reaction between a mixture of (2Z,4E)-
2,3,5-triphenylpenta-2,4-dienal 1f (0.50 g, 1.61 mmol), sarcosine
(0.28 g, 3.15 mmol) was carried out in toluene (50 mL), as described
above. After cooling to room temperature, the mixture was filtered
to remove any solid. Evaporation of the solvent under reduced
pressure gave (E)-2,3-dihydro-1-methyl-3,4-diphenyl-3-(20-phe-
nyl-ethenyl)-1H-pyrrole 4f as a yellow oil (0.44 g, 81%); (found:
MHþ, 338.191. Calcd for C25H24N: MHþ, 338.190); nmax (liquid film)/
(270 MHz, CDCl3)
d
ppm 3.54 (3H, s, NCH3), 6.55 (2H, s), 6.97e7.10
ppm 36.7 (CH3), 121.7 (2ꢂ
(10H, m); 13C NMR (67.5 MHz, CDCl3)
d
CH), 123.9 (2ꢂ quat), 125.9 (2ꢂ CH), 128.5 (4ꢂ CH), 128.8 (4ꢂ CH),
136.3 (2ꢂ quat); and 5-bromo-2,3-dihydro-2-methyl-4-phenyl-1H-
2-benzazepine 6h asþa colourless crystals (80 mg, 18%); mp
85e87 ꢁC; (found: MH , 314.055 and 316.054. Calcd for C17H17NBr:
MHþ, 314.054 and 316.052); nmax (KBr)/cmꢀ1 1491 (C]C); 1H NMR
cmꢀ1 1599 (C]C), 1495 (C]C); 1H NMR (270 MHz, CDCl3)
d ppm
2.72 (3H, s, NCH3), 3.23 (1H, d, J¼8.6 Hz, H-2a), 3.68 (1H, d, J¼8.6 Hz,
H-2b), 6.63 (1H, d, J¼16.5 Hz, ]CH), 6.67 (1H, s, ]CH, H-5), 6.87
(1H, d, J¼16.5 Hz, ]CH), 7.09e7.32 (11H, m, AreH), 7.38 (2H, m,
(270 MHz, CDCl3)
d
ppm 2.30 (3H, s, NCH3), 3.08 (2H, s), 3.62 (2H, s),
ppm 43.9 (CH3),
7.17e7.67 (9H, m); 13C NMR (67.5 MHz, CDCl3)
d
58.4 (CH2), 59.2 (CH2), 121.9 (quat), 127.9 (CH), 128.3 (CH), 128.6 (2ꢂ
CH), 128.7 (2ꢂ CH), 129.2 (CH), 129.8 (CH), 129.9 (CH), 135.6 (quat),
140.1 (quat), 141.0 (quat), 143.4 (quat).
AreH), 7.49 (2H, m, AreH); 13C NMR (67.5 MHz, CDCl3)
d ppm 39.7
(CH3), 58.6 (quat), 71.1 (CH2),118.8 (quat),124.0 (CH),124.7 (2ꢂ CH),
126.40 (CH), 126.43 (2ꢂ CH), 127.2 (CH), 127.8 (2ꢂ CH), 128.1 (2ꢂ
CH), 128.3 (2ꢂ CH), 128.5 (2ꢂ CH), 129.4 (CH), 132.8 (CH), 135.2
(quat), 137.6 (quat), 140.5 (CH), 145.5 (quat).
3.2.9. 2,3-Dihydro-1,6-dimethyl-3,5-diphenyl-1H-azepine
6i. A
mixture of (2E,4E)-3,5-diphenyl-2-methylpenta-2,4-dienal 1i
(0.50 g, 2.02 mmol), sarcosine (0.36 g, 4.04 mmol) in toluene
(70 mL) was heated at reflux overnight, as described above. After
cooling to room temperature, the mixture was filtered to remove
any solid. Evaporation of the solvent under reduced pressure gave
2,3-dihydro-1,6-dimethyl-3,5-diphenyl-1H-azepine 6i as a yellow
oil (0.42 g, 76%); (found: MHþ, 276.174. Calcd for C20H22N: MHþ,
3.2.6. (10Z)-2,3-Dihydro-2,4-dimethyl-5-(20-phenylethenyl)-1H-2-
benzazepine 6e. The reaction between (2Z,4Z)- and (2Z,4E)-2-
methyl-3,5-diphenylpenta-2,4-dienal 1e and 1d (3:1, 0.30 g,
1.2 mmol), and sarcosine (0.22 g, 2.4 mmol) was carried out in
toluene (50 mL), as described above. The solid was removed by
filtration and the solvent was evaporated under reduced pressure.
Flash chromatography of the residue on silica, eluting with hex-
ane/ethyl acetate (90:10 to 70:30), gave (Z)-2,3-dihydro-2,4-
276.175); 1H NMR (270 MHz, CDCl3)
d ppm 1.63 (3H, s, CH3), 2.73
(3H, s, NCH3), 3.35 (2H, m, CH2), 3.53 (1H, m, H-3), 5.76 (1H, d,
J¼4.6 Hz, ]CH, H-4), 6.16 (1H, s, ]CH, H-7), 7.14e7.29 (10H, m,
dimethyl-5-(20-phenylethenyl)-1H-2-benzazepine 6e as
a
pale
AreH); 13C NMR (67.5 MHz, CDCl3)
d ppm 22.7 (CH3), 45.5 (CH), 47.8
yellow oil (0.15 g, 45%); (Found: MHþ, 276.175. Calcd for C20H22N:
(NCH3), 64.1 (CH2), 102.5 (quat), 126.1 (CH), 126.2 (CH), 127.6 (4ꢂ
CH), 128.4 (2ꢂ CH), 128.5 (2ꢂ CH), 131.1 (CH), 138.7 (CH), 142.4
(quat), 144.2 (quat), 144.6 (quat).
MHþ, 276.175); nmax (liquid film)/cmꢀ1 1597 (C]C); 1H NMR
(270 MHz, CDCl3)
d ppm 1.92 (3H, s, CH3), 2.46 (3H, s, NCH3), 2.79
(2H, s, CH2), 3.55 (2H, s, CH2), 6.29 (1H, d, J¼12.3 Hz, ]CH), 6.33
(1H, d, J¼12.3 Hz, ]CH), 7.12-7.27 (9H, m, AreH); 13C NMR
3.2.10. 3,4,6,7,8-Pentahydro-2-methyl-4-phenyl-2H-cyclopenta[c]
azepine 6j. (10E)-1-Formyl-2-(20-phenylethenyl)cyclopentene 1j
(0.50 g, 2.53 mmol) was reacted with sarcosine (0.45 g, 5.06 mmol)
as described above. Removal of the solid by filtration and the sol-
vent by evaporation under reduced pressure gave 3,4,6,7,8-
pentahydro-2-methyl-4-phenyl-2H-cyclopenta[c]azepine 6j as
a yellow oil (0.47 g, 82%); (found: MHþ, 226.159. Calcd for C16H20N:
MHþ, 226.159); nmax (liquid film)/cmꢀ11604 (C]C), 1492 (C]C); 1H
(67.5 MHz, CDCl3)
d ppm 22.6 (CH3), 44.0 (NCH3), 58.5 (CH2), 58.7
(CH2), 127.3 (CH), 127.41 (CH), 127.7 (CH), 127.9 (CH), 128.3 (2ꢂ
CH), 128.7 (2ꢂ CH), 129.0 (CH), 130.1 (CH), 132.5 (CH), 134.1 (quat),
135.6 (quat), 135.9 (quat), 138.0 (quat), 141.1 (quat) and (E)-2,3-
dihydro-1,4-dimethyl-3-phenyl-3-(20-phenylethenyl)-1H-pyrrole
4d (0.013 g, 4%) for which the spectroscopic data was identical to
that presented above.
NMR (270 MHz, CDCl3)
d
ppm 1.67 (2H, m, CH2), 2.49 (4H, m, 2ꢂ
3.2.7. 2,3-Dihydro-2-methyl-4-phenyl-1H-2-benzazepine
6g. A
CH2), 2.61 (3H, s, NCH3), 3.02 (1H, dd, J¼12.5 and 5.9 Hz, H-3a), 3.22
(1H, dd, J¼12.5 and 2.0 Hz, H-3b), 3.57 (1H, m, H-4), 5.53 (1H, d,
J¼4.0 Hz, ]CH, H-5), 6.12 (1H, s, ]CH, H-1), 7.11e7.29 (5H, m,
mixture of (Z)-2,3-diphenyl-2-propenal 1g (0.1 g, 0.5 mmol) and
sarcosine (0.1 g, 1.1 mmol) in anhydrous toluene (20 mL) was
heated at reflux overnight as described above. After cooling to room
temperature, the mixture was filtered to remove any solid. The
solvent was evaporated under reduced pressure and the residue
was separated by column chromatography on silica, eluting with
ether/ethyl acetate (90 : 10) to give 2,3-dihydro-2-methyl-4-
AreH); 13C NMR (67.5 MHz, CDCl3)
d ppm 25.6 (CH2), 34.1 (CH2),
37.1 (CH2), 44.3 (CH), 48.8 (NCH3), 60.1 (CH2), 111.6 (quat), 119.6
(CH), 125.9 (CH), 127.7 (2ꢂ CH), 128.1 (2ꢂ CH), 134.5 (CH), 141.4
(quat), 144.8 (quat).
phenyl-1H-2-benzazepine 6g as
(found: MHþ, 236.144. Calcd for C17H18N: MHþ, 236.143); nmax
(KBr)/cmꢀ1 1490 (C]C); 1H NMR (270 MHz, CDCl3)
ppm 2.42 (3H,
s, NCH3), 3.67 (2H, s), 3.78 (2H, s), 6.78 (1H, s, H-5), 7.12e7.43 (9H,
m); 13C NMR (67.5 MHz, CDCl3)
ppm 43.4 (CH3), 60.5 (CH2), 60.6
(CH2), 126.8 (2ꢂ CH), 127.6 (CH), 127.8 (CH), 127.9 (CH), 128.9 (2ꢂ
a
yellow oil (35 mg, 30%);
3.2.11. 3,4,6,7,8-Pentahydro-2,4-dimethyl-4-phenyl-2H-cyclopenta
[c]azepine 6k. The reaction between (1’E)-1-formyl-2-(20-methyl-
20-phenylethenyl)cyclopentene 1k (0.65 g, 3.07 mmol) and
sarcosine (0.55 g, 6.18 mmol) using the method above gave
3,4,6,7,8-pentahydro-2,4-dimethyl-4-phenyl-2H-cyclopenta[c]aze-
pine 6k as a brown oil (0.61 g, 84%); (found: MHþ, 240.174. Calcd for
d
d

3628
W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
C17H22N: MHþ, 240.175); nmax (liquid film)/cmꢀ1 1608 (C]C), 1493
(C]C); 1H NMR (270 MHz, CDCl3)
ppm 1.48 (3H, s, CH3), 1.78
(CH2), 54.9 (CH2),110.0 (quat),124.4 (CH), 125.1 (2ꢂ CH), 126.5 (CH),
127.9 (CH), 128.0 (CH), 128.05 (CH), 128.1 (2ꢂ CH), 135.4 (quat),
137.5 (CH), 141.3 (quat), 144.9 (quat).
d
(2H, m, CH2), 2.62e2.66 (4H, m, 2ꢂ CH2), 2.66 (3H, s, NCH3), 3.12
(2H, s, NCH2), 5.47 (1H, s, ]CH), 6.12 (1H, s, ]CH), 7.21e7.39
(5H, m, AreH); 13C NMR (67.5 MHz, CDCl3)
d
ppm 25.65 (CH3), 25.70
3.2.16. 2,3-Dihydro-4-(10-naphthyl)-2-methyl-1H-2-benzazepine
(CH2), 34.2 (CH2), 37.3 (CH2), 44.8 (NCH3), 48.1 (quat), 65.9 (NCH2),
109.9 (quat), 124.0 (CH), 125.6 (CH), 126.7 (2ꢂ CH), 127.8 (2ꢂ CH),
134.8 (CH), 139.7 (quat), 147.5 (quat).
6p. This was prepared, as described above, from a mixture of (1’E)-
1-formyl-2-[20-(100-naphthyl)ethenyl]benzene
1p
(0.85
g,
3.29 mmol) and sarcosine (0.44 g, 4.94 mmol) in THF (70 mL). The
usual work-up, and chromatography on silica, eluting with petro-
leum ether 60e80 ꢁC/diethyl ether (90 : 10), gave 2,3-dihydro-2-
methyl-4-(10-naphthyl)-1H-2-benzazepine as a pale yellow oil 6p
(0.65 g, 69%); (found: MHþ, 286.159. Calcd for C21H20N: MHþ,
286.159); nmax (liquid film)/cmꢀ1 1597 (C]C), 1574 (C]C); 1H NMR
3.2.12. 3,4,6,7,8,9-Hexahydro-2-methyl-4-phenyl-2H-2-benzazepine
6l. This was prepared, as above, from (1’E)-1-formyl-2-(20-phe-
nylethenyl)cyclohexene 1l (0.70 g, 3.30 mmol), sarcosine (0.59 g,
6.63 mmol) and anhydrous toluene (70 mL), to give 3,4,6,7,8,9-
hexahydro-2-methyl-4-phenyl-2H-2-benzazepine 6l as
a
deep
(270 MHz, CDCl3) d ppm 2.58 (3H, s, NCH3), 3.81 (2H, s, CH2), 4.28
blue oil (0.62 g, 78%); (found: MHþ, 240.175. Calcd for C17H22N:
(2H, s, CH2), 5.67 (1H, s, ]CH, H-5), 7.10 (1H, m, AreH), 7.19 (1H, m,
AreH), 7.23e7.44 (5H, m, AreH), 7.61e7.80 (3H, m, AreH), 8.20
MHþ, 240.175); nmax (liquid film)/cmꢀ1 1602 (C]C), 1493 (C]C); 1H
NMR (270 MHz, CDCl3)
d
ppm 1.72 (4H, m, 2ꢂ CH2), 2.15 (4H, m, 2ꢂ
(1H, m, AreH); 13C NMR (67.5 MHz, CDCl3)
d ppm 37.4 (NCH3), 43.0
CH2), 2.63 (1H, m, H-4), 2.67 (3H, s, NCH3), 3.03 (1H, dd, J¼14.5 and
6.6 Hz, H-3a), 3.26 (1H, dd, J¼14.5 and 7.9 Hz, H-3b), 5.26 (1H, d,
J¼3.3 Hz, ]CH, H-5), 5.70 (1H, s, ]CH, H-1), 7.11e7.29 (5H, m,
(CH2), 54.9 (CH2), 110.4 (quat), 125.31 (CH), 125.33 (CH), 125.5 (CH),
126.1 (CH), 126.3 (CH), 126.37 (CH), 126.43 (CH), 127.8 (CH), 127.9
(CH), 128.2 (CH), 128.3 (CH), 131.9 (quat), 133.9 (quat), 135.7 (quat),
138.0 (CH), 141.8 (quat), 143.6 (quat).
AreH); 13C NMR (67.5 MHz, CDCl3)
d ppm 24.2 (CH2), 26.3 (CH2),
31.2 (CH2), 43.7 (CH2), 45.2 (CH), 45.9 (NCH3), 63.5 (NCH2), 110.6
(quat), 121.3 (CH), 126.1 (CH), 126.9 (2ꢂ CH), 128.2 (2ꢂ CH), 135.5
(quat), 136.8 (CH), 146.3 (quat).
3.2.17. 4-Cyano-2,3-dihydro-2-methyl-1H-2-benzazepine
6q. The
reaction between (1’E)-2-(20-cyanoethenyl)benzaldehyde 1q
(0.50 g, 3.18 mmol) and sarcosine (0.43 g, 4.83 mmol) in THF
(70 mL), as described above, gave, after column chromatography on
neutral aluminium oxide, eluting with hexane/ether (75:25), 2,3-
dihydro-2-methyl-4-cyano-1H-2-benzazepine 6q as a pale yellow
oil (0.37 g, 63%); (found: MHþ, 185.108. Calcd for C12H13N2: MH,
185.107); nmax (liquid film)/cmꢀ1 2177 (C^N), 1624 (C]C); 1H NMR
3.2.13. 2,3-Dihydro-2-methyl-4-phenyl-1H-thieno[3,2-c]azepine
6m. This was prepared, as above, from (1’E)-2-(20-phenylethenyl)
thiophene-3-carboxaldehyde 1m (0.50 g, 2.34 mmol), sarcosine
(0.32 g, 3.60 mmol) in dry THF (70 mL) with refluxing for 12 h. The
usual work-up as above and chromatography on silica, eluting with
petroleum ether 60e80 ꢁC/diethyl ether (70:30) gave 2,3-dihydro-
2-methyl-4-phenyl-1H-thieno[3,2-c]azepine 6m as a brown oil
(0.39 g, 70%); (found: MHþ, 242.100. Calcd for C15H16NS, MHþ,
242.100); nmax (liquid film)/cmꢀ1 1594 (C]C), 1492 (C]C); 1H NMR
(270 MHz, CDCl3)
(2H, s, CH2), 6.41 (1H, s, ]CH, H-5), 7.13e7.30 (4H, m, AreH); 13C
NMR (67.5 MHz, CDCl3) ppm 32.2 (NCH3), 44.6 (CH2), 54.0 (CH2),
d ppm 2.96 (3H, s, NCH3), 3.64 (2H, s, CH2), 4.36
d
102.4 (quat), 124.6 (CN), 127.3 (CH), 128.1 (CH), 128.5 (CH), 128.9
(CH), 134.5 (quat), 139.9 (quat), 149.5 (CH).
(270 MHz, CDCl3)
d ppm 2.81 (3H, s, NCH3), 3.99 (2H, s, CH2), 4.18
(2H, s, CH2), 6.06 (1H, s, ]CH, H-5), 6.85 (1H, d, J¼5.3 Hz, H-7), 6.95
(1H, d, J¼5.3 Hz, H-6), 7.11 (1H, m, AreH), 7.24 (4H, m, AreH); 13C
3.2.18. 2,3-Dihydro-4-(40-methoxyphenyl)-2-methyl-1H-2-
benzazepine
NMR (67.5 MHz, CDCl3)
d
ppm 29.2 (NCH3), 45.3 (CH2), 50.8 (CH2),
6r. (1’E)-1-Formyl-2-[20-(400-methoxyphenyl)
110.6 (quat), 120.3 (CH), 124.8 (CH), 125.1 (2ꢂ CH), 128.0 (CH), 128.2
ethenyl]benzene 1r (0.70 g, 2.94 mmol) was reacted with sar-
cosine (0.39 g, 4.38 mmol) as above to give, after column chro-
matography on neutral aluminium, eluting with petroleum
(60e80 ꢁC)/diethyl ether (90:10), 2,3-dihydro-2-methyl-4-(40-
(2ꢂ CH), 134.0 (quat), 138.2 (quat), 139.2 (CH), 144.7 (quat).
3.2.14. 2,3-Dihydro-2,4-dimethyl-1H-2-benzazepine
6n. (1’E)-1-
Formyl-2-(10-prop-10-enyl)benzene 1n (0.45 g, 3.08 mmol) was
reacted with sarcosine (0.55 g, 6.18 mmol) in dry THF (50 mL) using
the method above, to give, after column chromatography on neutral
aluminium oxide eluting with hexane/ether (90:1), 2,3-dihydro-
2,4-dimethyl-1H-2-benzazepine as a pale yellow oil 6n (0.31 g,
58%); (found: MHþ, 174.129. Calcd for C12H16N: MHþ, 174.128); nmax
(liquid film)/cmꢀ1 1661 (C]C), 1606 (C]C); 1H NMR (270 MHz,
methoxyphenyl)-1H-2-benzazepine 6r as a pale yellow oil
(0.50 g, 65%); (found: MHþ, 266.154. Calcd for C18H20NO: MH,
266.154); nmax (liquid film)/cmꢀ1 1604 (C]C), 1576 (C]C), 1512
(C]C); 1H NMR (270 MHz, CDCl3)
d ppm 2.69 (3H, s, NCH3), 3.75
(3H, s, OCH3), 3.91 (2H, s, CH2), 4.27 (2H, s, CH2), 5.78 (1H, s, ]
CH, H-5), 6.81 (2H, d, J¼8.6 Hz, H-30,50), 7.12e7.21 (6H, m, AreH);
13C NMR (67.5 MHz, CDCl3)
d ppm 35.6 (NCH3), 43.5 (CH2), 55.0
CDCl3)
4.06 (2H, s, CH2), 5.39 (1H, s, ]CH, H-5), 6.93e7.21 (4H, m, AreH);
13C NMR (67.5 MHz, CDCl3)
ppm 24.5 (CH3), 36.9 (NCH3), 42.2
d
ppm 1.66 (3H, s, CH3), 2.43 (3H, s, NCH3), 3.36 (2H, s, CH2),
(CH2), 55.2 (OCH3), 110.4 (quat), 113.5 (2ꢂ CH), 126.36 (2ꢂ CH),
126.39 (CH), 127.8 (CH), 128.0 (2ꢂ CH), 135.5 (quat), 136.4 (CH),
137.7 (quat), 141.4 (quat), 157.1 (quat).
d
(CH2), 55.2 (CH2), 107.6 (quat), 125.8 (CH), 127.1 (CH), 127.8 (CH),
127.9 (CH), 133.5 (CH), 135.6 (quat), 140.9 (quat).
3.2.19. 2,3-Dihydro-2-methyl-4-(40-nitrophenyl)-1H-2-benzazepine
6s. This was prepared from a mixture of (1’E)-2-[20-(400-nitro-
phenyl)ethenyl]benzaldehyde 1s (0.35 g, 1.38 mmol) and sarcosine
(0.18 g, 2.02 mmol), in THF (50 mL) was refluxed for 6 h. Work-up as
above and column chromatography on silica, eluting with petro-
leum 60e80 ꢁC/diethyl ether (70 : 30), gave 2,3-dihydro-2-methyl-
4-(40-nitrophenyl)-1H-2-benzazepine 6s as a red oil (0.31 g, 79%);
(found: MHþ, 281.129. Calcd for C17H17N2O2: MH, 281.128); nmax
(liquid film)/cmꢀ1 1621 (C]C), 1572 (N]O), 1319 (N]O); 1H NMR
3.2.15. 2,3-Dihydro-2-methyl-4-phenyl-1H-2-benzazepine 6o. This
was prepared, as described above, from a mixture of (1’E)-1-formyl-
2-(20-phenylethenyl)benzene 1o (0.42 g, 2.02 mmol) and sarcosine
(0.27 g, 3.03 mmol) in THF (70 mL) to give, after column chroma-
tography on silica eluting with hexane/ethyl acetate (90:10), 2,3-
dihydro-2-methyl-4-phenyl-1H-2-benzazepine 6o as a brown oil
(0.35 g, 74%); (found: MHþ, 236.143. Calcd for C17H18N: MHþ,
236.143); nmax (liquid film)/cmꢀ1 1631 (C]C), 1592 (C]C), 1492
(270 MHz, CDCl3)
d ppm 2.95 (3H, s, NCH3), 3.97 (2H, s, CH2), 4.41
(C]C); 1H NMR (270 MHz, CDCl3)
(2H, s, CH2), 4.28 (2H, s, CH2), 5.88 (1H, s, ]CH, H-5), 7.05e7.28 (9H,
m, AreH); 13C NMR (67.5 MHz, CDCl3)
ppm 35.1 (NCH3) 43.7
d
ppm 2.72 (3H, s, NCH3), 3.94
(2H, s, CH2), 6.25 (1H, s, ]CH, H-5), 7.17e7.32 (6H, m, AreH), 8.08
(2H, d, J¼9.2 Hz, H-30,50); 13C NMR (67.5 MHz, CDCl3)
d ppm 34.0
d
(NCH3), 44.6 (CH2), 54.7 (CH2), 105.9 (quat), 123.6 (2ꢂ CH), 124.0

W. Zhang et al. / Tetrahedron 70 (2014) 3621e3629
3629
(2ꢂ CH) 127.0 (CH), 128.0 (CH), 128.2 (CH), 128.5 (CH), 135.0 (quat),
2.39 mmol) and sarcosine (0.43 g, 4.83 mmol) in THF (70 mL) was
refluxed for 16 h. Chromatography on silica, eluting with hexane/
diethyl ether (80 : 20) gave 2,3-dihydro-2-methyl-1H-thieno[2,3-d]
[2]benzazepine 6w as a pale yellow oil (0.35 g, 69%); (found: MHþ,
216.084. Calcd for C13H14NS: MH, 216.084); nmax (liquid film)/cmꢀ1
140.5 (quat), 140.9 (CH), 143.6 (quat), 151.7 (quat).
3.2.20. 4-(40-Cyanophenyl)-2,3-dihydro-2-methyl-1H-2-benzazepine
6t. A mixture of (1’E)-2-[20-(400-cyanophenyl)ethenyl]benzalde-
hyde 1t (0.50 g, 3.18 mmol) and sarcosine (0.43 g, 4.83 mmol) in dry
THF (70 mL) was refluxed for 8 h. The work-up as above and
chromatography on silica, eluting with petroleum ether 60e80 ꢁC/
diethyl ether (75:25) gave 2,3-dihydro-2-methyl-4-(40-cyano-
phenyl)-1H-2-benzazepine 6t as a pale yellow oil (0.44 g, 75%);
(found: MHþ, 261.139. Calcd for C18H17N2: MH, 261.139); nmax (liq-
uid film)/cmꢀ1 2218 (C^N), 1587 (C]C), 1502 (C]C); 1H NMR
1603 (C]C), 1487 (C]C); 1H NMR (270 MHz, CDCl3)
d
ppm 2.40
(3H, s, NCH3), 3.37 (2H, s, CH2), 3.57 (2H, s, CH2), 7.16e7.43 (6H, m,
AreH); 13C NMR (67.5 MHz, CDCl3)
ppm 43.3 (NCH3), 51.4 (CH2),
d
58.2 (CH2), 123.3 (CH), 126.5 (CH), 126.68 (CH), 126.74 (CH), 127.5
(CH), 130.3 (CH), 134.3 (quat), 135.8 (quat), 137.0 (quat), 140.4
(quat).
(270 MHz, CDCl3)
d ppm 2.89 (3H, s, NCH3), 3.93 (2H, s, CH2), 4.38
3.3. Molecular modelling
(2H, s, CH2), 6.11 (1H, s, ]CH, H-5), 7.18e7.26 (4H, m, AreH), 7.29
(2H, d, J¼8.9 Hz, AreH), 7.49 (2H, d, J¼8.9 Hz, AreH); 13C NMR
Density functional theory (DFT) calculations were carried out at
the B3LYP/6-31G*10,11 level in Gaussian09 software.12 Reactants and
products were fully geometry optimised without symmetry con-
straints, and characterised as true minima via harmonic frequency
calculation. Transition states were then located using quadratic
synchronous transit (QST) methods,13 and characterised by their
harmonic frequencies.
(67.5 MHz, CDCl3)
d ppm 34.1 (CH3), 44.3 (CH2), 54.7 (CH2), 106.5
(CN), 119.8 (quat), 124.4 (2ꢂ CH), 126.9 (CH), 128.0 (CH), 128.2 (CH),
128.3 (CH), 128.7 (quat), 132.1 (2ꢂ CH), 135.1 (quat), 140.0 (CH),
140.7 (quat), 149.5 (quat).
3.2.21. 4-(40-Chlorophenyl)-2,3-dihydro-2-methyl-1H-2-benzazepine
6u. A mixture of (1’E)-2-[20-(400-chlorophenyl)ethenyl]benzalde-
hyde 1u (0.65 g, 2.68 mmol) and sarcosine (0.36 g, 4.04 mmol) in
dry THF (70 mL) was refluxed for 8 h. The usual work-up as above
and chromatography on silica, eluting with petroleum ether
60e80 ꢁC/diethyl ether (80:20) gave 2,3-dihydro-2-methyl-4-(40-
chlorophenyl)-1H-2-benzazepine 6u as a pale yellow oil (0.61 g,
78%); (found: MHþ, 272.101. Calcd for C17H17N37Cl: MH, 272.102);
Acknowledgements
We thank the EPSRC UK National Mass Spectrometry Facility,
Swansea University, U.K. for providing all accurate mass
measurements.
1H NMR (270 MHz, CDCl3)
CH2), 4.24 (2H, s, CH2), 5.84 (1H, s, ]CH, H-5), 6.94e7.20 (8H, m,
AreH); 13C NMR (67.5 MHz, CDCl3)
ppm 34.8 (NCH3), 43.5 (CH2),
54.6 (CH2),108.2 (CH),126.0 (2ꢂ CH),126.4 (CH),127.82 (CH),127.88
(CH), 128.0 (2ꢂ CH), 129.5 (quat), 130.3 (quat), 135.2 (quat), 137.6
(CH), 140.9 (quat), 143.3 (quat).
d ppm 2.70 (3H, s, NCH3), 3.85 (2H, s,
d
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.03.078.
3.2.22. 1,4-Diaza-4-methyl-2,6-dioxo-1-phenyl-3-[20-{200-(10E)-phe-
nylethenyl}phenyl]bicyclo[3.3.0]octane 12. A mixture of (10E)-1-
formyl-2-(20-phenylethenyl)benzene 1o (0.42 g, 2.02 mmol), sar-
cosine (0.27 g, 3.03 mmol), N-phenylmaleimide (0.21 g, 1.2 mmol)
References and notes
1. (a) Tsuge, O.; Kanemasa, S. In Advances in Heterocyclic Chemistry; Katritzky, A. R.,
Ed.; Academic: San Diego, CA, 1989; Vol. 45, pp 232e349; (b) Grigg, R.; Srid-
haran, V. In Advances in Cycloaddition; Curran, D. P., Ed.; JAI: London, 1993; Vol.
3, pp 161e204.
2. (a) Taylor, E. C.; Turchi, I. J. Chem. Rev. 1979, 79, 181e231; (b) Huisgen, R. Angew.
Chem., Int. Ed. Engl. 1980, 19, 947e973.
3. (a) Arany, A.; Groundwater, P. W.; Nyerges, M. Tetrahedron Lett. 1998, 38,
3267e3268; (b) Arany, A.; Bendell, D.; Groundwater, P. W.; Garnett, I.; Nyerges,
M. J. Chem. Soc., Perkin Trans. 1 1999, 2605e2608.
4. (a) Marx, K.; Eberbach, W. Tetrahedron 1997, 51, 14687e14700; (b) Ground-
water, P. W.; Nyerges, M. In Adv. Heterocycl. Chem.; Katritzky, A. R., Ed.; Aca-
demic: 1999; Vol. 73, pp 97e129.
5. (a) Rizzi, G. P. J. Org. Chem. 1970, 35, 2069e2072; (b) Grigg, R.; Idle, J.;
McMeekin, P.; Vipond, D. J. Chem. Soc., Chem. Commun. 1987, 49e51.
6. (a) Heine, H.; Peavy, R. Tetrahedron Lett. 1965, 3123e3126; (b) Huisgen, R.;
Scheer, W.; Mader, H. Angew. Chem., Int. Ed. Engl. 1969, 8, 602e604.
7. (a) Grigg, R.; Gunaratne, H. Q. N.; Kemp, J. J. Chem. Soc., Perkin Trans. 1 1984,
41e46; (b) Grigg, R.; Gunaratne, H. Q. N. Tetrahedron Lett. 1983, 24, 4457e4460;
(c) Grigg, R. Chem. Soc. Rev. 1987, 16, 89e121.
8. Munro, D. P.; Sharp, J. T. J. Chem. Soc., Perkin Trans. 1 1984, 849e858.
9. Sucrow, W.; Chondromatidis, G. Chem. Ber. 1970, 103, 1759e1766.
10. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648e5652; (b) Lee, C.; Yang, W.; Parr, R.
G. Phys. Rev. B 1988, 37, 785e789.
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Hariharan, P. C.; Pople, J. A. Theor. Chem. Acc. 1973, 28, 213e222.
12. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B., et al. Gaussian09 Revision A.02;
Gaussian: Wallingford CT, 2009.
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49e56.
ꢁ
and 4 A molecular sieves (2 g) in anhydrous THF (70 mL) was
heated at reflux, under dry nitrogen, for 12 h. After cooling, the
solid was removed by filtration and the solvent was evaporated
under reduced pressure. Column chromatography of the residue on
silica, eluting with petroleum ether 60e80 ꢁC/diethyl ether (90:10
to 70:30), gave 1,4-diaza-4-methyl-2,6-dioxo-1-phenyl-3-[20-{200-
(E)-phenyethenyl}-phenyl]bicyclo[3.3.0]octane 12 as a white solid
(0.27 g, 55%), mp 77e79 ꢁC; (Found: MHþ, 409.192. Calcd for
C
27H25N2O2: MH, 409.191); nmax (KBr)/cmꢀ1 1778 (C]O), 1712 (C]
O), 1599 (C]C), 1496 (C]C); 1H NMR (270 MHz, CDCl3)
ppm 2.19
d
(3H, s, NCH3), 2.68 (1H, m, H-5a), 3.60 (1H, m, H-2a), 3.70 (2H, m,
CH2, H-5), 3.95 (1H, d, J¼5.9 Hz, H-3), 6.92 (1H, d, J¼16.2 Hz, ]CH),
7.23e7.62 (14H, m, AreH), 7.86 (1H, d, J¼16.2 Hz, ]CH); 13C NMR
(67.5 MHz, CDCl3)
d ppm 39.1 (NCH3), 44.4 (CH2), 53.9 (CH), 57.8
(CH), 70.5 (CH), 126.45 (2ꢂ CH), 126.5 (CH), 126.7 (2ꢂ CH), 127.1
(CH),127.7 (CH),128.0 (CH),128.2 (CH),128.4 (CH),128.6 (CH),128.7
(2ꢂ CH), 129.1 (2ꢂ CH), 131.5 (CH), 131.7 (quat), 136.3 (quat), 137.5
(quat), 137.7 (quat), 176.3 (C]O), 176.8 (C]O).
3.2.23. 2,3-Dihydro-2-methyl-1H-thieno[2,3-d][2]benzazepine
6w. A mixture of 2-(3-thienyl)benzaldehyde 1w (0.45 g,