The triflic acid-mediated cyclisation of N-benzylcinnamanilides

Article abstract of DOI:10.1016/j.tet.2013.07.075

N-Benzylcinnamanilides cyclise with triflic acid to form 1-benzyl-4-aryl-2,4-dihydro-1H-quinolin-2-ones and 2,5-diaryl-benzazepin-3-ones. The product ratio is determined by the preferred orientation of the amide and by the electronics of the substituents. With ortho-substituted anilides, N-debenzylation also occurs to give 4-aryl-2,4-dihydro-1H-quinoline-2-ones.

Full text of DOI:10.1016/j.tet.2013.07.075

Tetrahedron 69 (2013) 8592e8601
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The triflic acid-mediated cyclisation of N-benzylcinnamanilides
*
Frank D. King , Stephen Caddick
Dept. of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 May 2013
Received in revised form 12 July 2013
Accepted 22 July 2013
Available online 5 August 2013
N-Benzylcinnamanilides cyclise with triflic acid to form 1-benzyl-4-aryl-2,4-dihydro-1H-quinolin-2-ones
and 2,5-diaryl-benzazepin-3-ones. The product ratio is determined by the preferred orientation of the
amide and by the electronics of the substituents. With ortho-substituted anilides, N-debenzylation also
occurs to give 4-aryl-2,4-dihydro-1H-quinoline-2-ones.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
4-Aryl-2,4-dihydro-1H-quinolin-2-ones
Triflic acid
2,5-Diaryl-benzazepin-3-ones
Intramolecular cyclisation
Carbocations
1. Introduction
vestigation on the effects of aromatic substituents on the reaction.
No aryl-substituted analogues of 5a have been prepared by this
We have recently reported the first synthesis of a 2,5-diaryl-
benzazepin-3-one 4a from the reaction of N-benzylcinnamanilide
2a with triflic acid (TfOH), but only in a 7% yield. The major product
was 1-benzyl-4-phenyl-2,4-dihydro-1H-quinoline-2-one 3a (80%
yield, Scheme 1).1 Benzazepin-3-ones have a wide range of bi-
ological activities2 and so we were interested in optimising this
reaction to provide novel N-aryl analogues. Within this context,
although polyphosphoric acid,3 TfOH4 and AlCl35-mediated cycli-
sations of 1a to 5a have been reported, there has been no in-
method, although recently analogues have been prepared by
a domino conjugate additionecyclisation reaction.6
2. Results and discussion
2.1. Cyclisations of N-benzylcinnamanilides-substituted
aniline
The TfOH-mediated cyclisation of 2a involves protonation of
both the amide and the double bond to give a dication, which reacts
with the anilide via an electrophilic addition to give 3a, or alter-
natively with the benzyl group to give 4a.1 It is also possible that the
cyclisation is reversible and that the ratio of isomers obtained re-
flects the thermodynamic equilibrium. To eliminate this possibility,
we heated 4a for 4 h under the cyclisation conditions, after which
time TLC showed only 4a, with no other products being formed.
The aim of this study was to enhance the formation of the
benzazepinones and we believed that incorporation of an electron
withdrawing group into the anilide would suppress formation
of the six-membered, and thus enhance formation of the seven-
membered ring product. The N-benzylcinnamanilides required
for our studies were readily prepared in good overall yields from
cinnamoyl chloride and 2 equiv of the aniline,7 followed by N-
benzylation of the cinnamanilide with benzyl bromide and
KOtBu in THF.
O
R
N
+
O
N
R
O
N
1a R = H
5a R = H
4a
2a R = CH2Ph
3a R = CH2Ph
Scheme 1. TfOH-mediated cyclisation of N-benzylcinnamanilide.
Reaction of both the p-nitro-2b (Table 1 entry 2) and m-nitro-2c
(entry 3) compounds with TfOH gave none of the desired
* Corresponding author. Tel.: þ44 (0)207 6793554; e-mail addresses: f.d.king@
ucl.ac.uk, fd.king@btinternet.com (F.D. King).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.075

F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
8593
Table 1
TfOH-mediated cyclisation of N-benzylcinnamanilides 2aej
O
R
N
O
+
N
N
O
R
R
2a-i
4a-i
3a-i
Entry
Amide
R
Solvent
Acid
Temp ꢁC
Time h
Product
R
Yield %
Product
R
Yield %
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2e
2ec
2f
H
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
PhCl
TfOH
TfOH
TfOH
TfOH
TfOH
AlCl3
PPA
TfOH
TfOH
TfOH
TfOH
TfOH
65
65
65
65
65
100
110
65
80
65
1
2
2
4
1
0.5
0.5
3
2
18
8
3a
3b
3c
3d
3e
3e
3e
3f
H
6-NO2
5-,7-NO2
5-,7-CF3
80
0
0
20
78
86
80
67
71
0
4a
4b
4c
4d
4e
4e
4e
4f
H
7
0
0
65
18
5
4-NO2
3-NO2
3-CF3
4-Cl
4-Cl
4-Cl
40-NO2
30-NO2
30-CF3
40-Cl
a
6-Cl
6-Cl
6-Cl
6-F
40-Cl
d
40-Cl
2
4-F
CHCl3
DCE
CHCl3
CHCl3
CHCl3
60-F
18
16
85
61
74
9
2g
2h
2i
3,4-diCl
4-NH2
3-NH2
2-Cl
3g
3h
3i
di-Clb
6-NH2
5-,7-NH2
8-Cl
4g
4h
4i
30,40-diCl
40-NH2
30-NH2
20-Cl
10
11
12
65
65
0
0
2j
18
3j
4j
a
1:1 mixture of the 5- and 7-CF3 isomers.
1:1 mixture of the 5,6- and 6,7-dichloro isomers.
Plus 7% yield of NH quinolone 5e.
b
c
cyclisation, but rather hydrolysed the amide to give p-nitrophenyl-
benzylamine (95% yield) and m-nitrophenyl-benzylamine (92%
yield) respectively. We believed that the de-acylation was not
simply due to the strongly electron withdrawing nature of the
substituent, but was facilitated by protonation of the nitro group by
the triflic acid.8
The 4-chloro 2e (entry 5), 4-fluoro 2f (entry 8) and 3,4-dichloro
2g (entry 9) all gave a greater proportion of quinolone than ben-
zazepinone, though more benzazepinone than with 2a. In-
terestingly, the addition of the extra electron withdrawing 3-Cl
group in 2g made little difference to the product ratio. For 2e, AlCl3
(entry 6) and polyphosphoric acid (PPA, entry 7) were also in-
vestigated. Both gave good yields of 3e (86% and 80%, respectively)
with lower yields of 4e (5% and 2%, respectively). In addition, with
PPA the NH-quinolone 5e was also formed (7% yield). It has been
reported that aniline is specifically meta nitrated in TfOH because
the aniline is fully protonated,11 thus we believed that amino an-
alogues could give more of the benzazepinones. Consistent with
this, the cyclisation of both the 4-amino 2h (entry 10) and 3-amino
2i (entry 11) gave 4h (85% yield) and 4i (61% yield) respectively, the
other products isolated being the respective diamines, presumably
formed via cleavage of the amide.
The 2-chloro 2j was prepared in an attempt to increase the size
of the anilide, which would be expected to favour the rotamer with
the benzyl group trans to the carbonyl. However, 1H NMR studies
showed that 2a still exists as essentially one rotamer, but now with
no peak broadening at room temperature indicating a slow rotation
of the amide. NOESY studies again indicated that the predominant
conformation was with the anilide syn to the cinnamoyl group. In
addition, there appeared to be an NOE between aromatic protons of
the anilide and benzylic groups, indicating a proximity that may be
an edge/face interaction.12
In contrast, the m-CF3 2d (entry 4) readily cyclised to give
a much higher yield of the benzazepin-3-one 4d (65% yield). Sur-
prisingly, we still obtained some quinolin-2-one as an inseparable
1:1 mixture of the 5- and 7-CF3 isomers 3d (15% yield). In con-
sideration of this, in the 1H NMR spectrum of 2d at room tem-
perature, the signal for the ]CHCO proton is a broad doublet,
indicative of a rotation about the amide bond. Running the 1H NMR
at a ꢀ30 ꢁC sharpened the signals and showed that there was
a 97:3 ratio of rotamers about the amide bond. N,N-Disubstituted
amides normally exist as a mixture of rotamers, with the bulkier
group predominantly cis to the carbonyl. The molar refractivity of
Ph is 25.36, whereas for benzyl is 30.01,9 so one would expect the
benzyl group to be cis to the carbonyl, which the NMR studies
confirmed. The effect of the conjugation between the amide and
the olefin is known to reduce the rotational energy barrier,10 which
is consistant with the NMR showing that the amide group is rap-
idly rotating at room temperature. However, the predominant
conformation is with the anilide syn to the cinnamoyl, which fa-
vours six-membered ring formation and thus probably explains
the formation of 3d. Alternatively, the rotation about the amide
bond of the protonated cinnamanilide may be much slower than
that of the cinnamanilide, possibly due to enhanced conjugation
and/or H-bonding of the OH of the protonated carbonyl with
the benzyl group, which would again favour six-membered ring
formation.
Despite an apparently unfavourable conformational preference,
reaction of 2j with triflic acid gave mainly the seven-membered 4j
(74% yield), though the reaction rate was much slower (entry 12).
The NMR spectrum of 4j at room temperature showed that it exists
as a 1:1 ratio of conformers. In one conformation the 1-CH2 protons
Interestingly, in the NMR spectrum of the isomer mixture 3d,
the 7-CF3 isomer had the same conformation as 3a, indicated by the
4-CH signal being a triplet, equally split by the two 3-CH’s. How-
ever, for the 5-CF3 isomer, the 4-CH signal was a doublet, showing
coupling with only one of the 3-CH’s. In addition, whereas the CH2
protons of the benzyl group in both 3a and the 7-CF3 isomer were
non-equivalent, indicating a restricted rotation, the signal for the
benzylic CH2 protons of the 5-CF3 isomer was a singlet, indicating
equivalence through a facile rotation.
are widely spaced at
mation they are much closer, at
d
4.19 and 5.64, whereas in the other confor-
4.89 and 4.95. On heating in
d
DMSO-d6 to 373 K, a simpler, time averaged 1H NMR spectrum was
obtained. Although no 3j was detected, a small amount of 5j (w5%
yield) was obtained, identical to that obtained from the TfOH-
mediated cyclisation of 1j. We believe that six-membered ring
formation may be inhibited both by the removal of one of the
reacting sites, but also by a steric interaction between the N-benzyl
and the 2-chloro in the transition state.

8594
F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
2.2. Cyclisations of N-benzylcinnamanilidesdortho-substituted
anilines
the TfOH-mediated cyclisation of the NH amide 1n was investigated.
The conversion of 1n to 5n was found to be much slower. After
30 min reflux in CHCl3, by TLC there was still considerable amounts
of 1n remaining and it took 3 h before no 1n remained; compound
5n was obtained in 84% yield. In contrast, the conversion of 2n was
complete after 30 min reflux. If the reaction proceeds via pathway A
(Scheme 2), we would have expected the reaction of 1n to be com-
plete after 30 min. Therefore, although we could find no evidence of
3n as an intermediate in the reaction of 2n, we still conclude that
again the cyclisationproceeds via pathway B (Scheme 2), with the N-
de-benzylation now being so rapid that no 3n could be detected.
Because we obtained a good yield of the benzazepinone 4j
from 2j, we investigated the reaction with other ortho substituents
(Table 2). The 2-fluoro-cinnamanilide 2k (entry 2) gave a much lower
yield of benzazepinone 4k (30%) along with formation of much more
of the tetrahydroquinolone 5k (50%). These compounds were in-
separable on silica, but readily separable on alumina. Cyclisation of
the 2-bromo 2l (entry 3) gave a similar result to the 2-chloro 2j, the
benzazepinone 4l being the predominant product. For the formation
of 5l, we assume that 2l either de-benzylates to give 1l, which then
cyclises to 5l (Scheme 2, pathway A); or 2l cyclises to give 3l, which
rapidly de-benzylates, possibly facilitated by the bulk of the chloro
substituent (pathway B). Early termination of the reaction of 2l (entry
4) after 3 h gave a reduced yield of both 4l and 5l along with an in-
separable 4:1 mixture of 2l and 3l. In addition, reaction of 3l, pre-
pared from 5l by N-benzylation, with TfOH under the cyclisation
conditions gave 3l. Thus, it would appear that 2l cyclises to give 3l,
which then debenzylates to give 5l (Scheme 2, pathway B). We
prepared an authentic sample of 3l by N-benzylation of 5l and con-
firmed that 3l does rapidly N-debenzylate under the reaction
conditions.
2.3. Cyclisations of N-benzylcinnamanilidesdsubstituted
benzyl
The introduction of electron withdrawing groups into the benzyl
would be expected to reduce cyclisation to the benzazepinone and
were therefore not investigated. However, introduction of electron
donating groups would be expected to enhance benzazepinone
formation, though it may also enhance the rate of acid-mediated N-
debenzylation. For the study, the 4-chloroanilides were selected as
these would be more likely to give more crystalline products.
Table 2
TfOH-mediated cyclisation of N-benzylcinnamanilides 2jen
Cl
O
N
N
H
O
R
+
O
N
5e
N
O
R
R'
R
The cyclisation of the 4-methylbenzyl 2o led to the isolation
of three products (Table 3, entry 1), the N-4-methylbenzyl tetra
hydro-quinolinone 3o (39% yield), the NH tetrahydro-quinolinone
5e (47% yield) and the benzazepinone 4o (13% yield). However,
the overall yield of six-membered (86%) versus seven-membered
(13%) did not significantly differ from that for the N-benzyl 2e
(Table 1 entry 5, ratio 78:18). Increasing the activation of the benzyl
group with the 3-methyl (entry 2) gave only a marginal increase in
the proportion of seven-membered cyclisation, though the amount
of N-debenzylation was reduced. A 2.3:1 ratio of the 8- and 6-Me
isomers 4p was obtained. From a NOESY NMR experiment, the mi-
nor isomer showed strong NOE’s between the Me, and 5-CH and or-
tho 5-phenyl protons, whereas the major isomer showed no such
NOE’s. Greater activation of the benzyl group with the 3,5-
dimethyl 2q (entry 3) made no difference to the seven- to six-mem-
bered cyclisation ratio, though there was slight increase in
2i-m
4i-m
3i-m R’ = CH 2Ph
5i-m R’ = H
Entry Amide R
Time h Product Yield % Product Yield % Product Yield %
1
2
3
4
5
6
2j
2k
2l
2l
2m
2n
Cl
F
Br
Br
Me
18
18
18
3
3j
3k
3l
3l
3m
3n
0
0
4j
4k
4l
4l
4m
4n
74
30
83
50
0
5j
5k
5l
5
50
8
0
a
5l
5
3
0
0
5m
5n
95
58
OMe 0.5
0
a
See text.
Pathway B
N
O
O
Br
Table 3
TfOH-mediated cyclisation of N-benzylcinnamanilides 2oeq
N
3l
Br
N
H
O
O
O
Br
R
5l
R
N
NH
Cl
2l
+
Br
O
Pathway A
N
N
O
1l
R
Cl
Scheme 2. Possible mechanisms of formation of 5l.
Cl
2o-q
3o-q
4o-q
In contrast to 2jel, both the 2-methyl 2m (entry 5) and 2-
Entry Amide
R
Product Yield % Product Yield % Yield 5e%
methoxy 2n (entry 6) gave exclusively the NeH tetrahy-
droquinolones 5m and 5n, respectively, with relatively short re-
action times. The lower yield for 5n is probably due to hydrolysis of
the methoxy to the phenol, which would not have been isolated
from the basic work-up. To further investigate the formation of 5n,
1
2
3
2o
2p
2q
4-Me
3-Me
3,5-diMe 3q
3o
3p
39
62
57
4o
13
22
21
47
15
21
4pa
4q
a
Mixture of 6- and 8-Me isomers in a 1:2.3 ratio.

F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
8595
N-debenzylation. Thus, the addition of the electron donating sub-
stituents did not appear to significantly increase the amount of
benzazepinone, nor did it appear to enhance the rate of reaction,
as all three examples needed a similar reaction time.
131 (100), 103 (17), 91 (14%); HMRS (EI) Mþ, found 358.1307.
C23H18N2O3 requires 358.1312.
4.2.2. N-Benzyl-N-(3-nitrophenyl)-3-phenylacrylamide (2c). Following
the general procedure, N-(3-nitrophenyl)-3-phenylacrylamide13 1c
(1.4 g, 5.0 mmol) was converted to 2c (1.5 g, 84%) as a white solid; Rf
(70% EtOAc/petrol) 0.6; mp 78e79 ꢁC; dH (500 MHz, CDCl3) 5.13 (2H,
s), 6.27 (1H, d, J 15.4 Hz), 7.21e7.40 (11H, m), 7.53 (1H, t, J 8.1 Hz), 7.82
(1H, d, J 15.4 Hz), 8.01 (1H, s), 8.19 (1H, dd, J 1.2, 8.1 Hz); dC (125 MHz,
CDCl3) 53.3 (CH2), 117.7 (CH), 122.7 (CH), 123.1 (CH), 127.9 (CH), 128.1
(CH), 128.6 (CH), 128.8 (CH), 128.9 (CH), 130.2 (CH), 130.3 (CH), 134.8
(CH), 136.6 (C), 143.3 (C), 144.2 (CH), 148.9 (C), 165.9 (C); nmax (solid)
1651, 1601, 1528, 1385, 1352, 1329, 1240, 1204, 824, 759, 742, 698,
680 cmꢀ1; m/z (EI) 358 (100, Mþ), 131 (62), 103 (81), 91 (37), 77 (31%);
HMRS (EI) Mþ, found 358.131. C23H18N2O3 requires 358.1312.
3. Conclusion
In this paper, we have reported the results obtained from our
studies on the TfOH-mediated cyclisation of N-benzylcinnamani-
lides with respect to the ratio of six- to seven-membered ring for-
mation, with particular emphasis on favouring seven-membered,
benzazepinone formation. Our results confirm that, in general, six-
membered ring formation is more favoured. We suggest that this
may be due to the preferred conformational preference of the
N-benzylcinnamanilides having the anilide syn to the cinnamoyl
group. Nonetheless, moderate to good yields of benzazepinones can
be obtained by introducing strongly electron withdrawing groups
onto the anilide. In contrast, introduction of electron donating
groups onto the N-benzyl made little difference to the product ratio.
Of particular value was the selective formation of the amino-
substituted benzazepinones 4h and 4i as potentially useful in-
termediates to other analogues via, for example, the Sandmeyer
reaction.
4.2.3. N-Benzyl-N-(3-trifluoromethylphenyl)-3-phenylacrylamide
(2d). Following the general procedure, N-(3-trifluoromethylphenyl)-
3-phenyl-crylamide14 1d (1.8 g, 4.7 mmol) was converted to 2d,
purified by column chromatography, eluting with 3:1 petrol/DCM
and isolated as a white solid (1.8 g, 100%); Rf (DCM) 0.5; mp
64e66 ꢁC; dH (500 MHz, CDCl3) 5.06 (2H, s), 6.27 (1H, d, J 15.4 Hz),
7.20e7.36 (1H, m), 7.37 (1H, s), 7.48 (1H, t, J 7.9 Hz), 7.60 (1H, d, J
7.9 Hz), 7.79 (1H, d, J 15.4 Hz); dC (125 MHz, CDCl3) 53.3 (CH2), 118.1
(CH), 124.7 (CH), 125.2 (CH), 127.7 (CH), 128.0 (CH), 128.7 (CH), 128.8
(CH), 129.9 (CH), 130.1 (CH), 130.2 (C, q, J 33 Hz), 134.9 (C), 137.0 (C),
142.7 (C), 143.5 (CH), 165.9 (C); nmax (solid) 1652, 1604, 1493, 1448,
1388, 1339, 1321, 1310, 1238, 1211, 1171, 1163, 1123, 1094, 1072, 1033,
979, 870, 855, 806, 760, 700, 686, 675 cmꢀ1; m/z (EI) 381 (62, Mþ)
251 (19), 131 (100), 103 (21%); HMRS (EI): Mþ, found 381.1331.
C23H18F3NO requires 381.1335.
4. Experimental section
4.1. General
All reagents were commercially available, unless otherwise
specified and used without purification. The chloroform used was
stabilised with amylene. Commercial dry benzene was stored over
molecular sieves. Petroleum ether was 40e60 ꢁC fraction. Infrared
spectra were run neat on a Perkin Elmer 100 FT IR spectrometer.
Solution 1H and 13C NMR spectra, in CDCl3 unless otherwise stated,
were recorded on Bruker NMR spectrometer DRX500 or Avance III
400, equipped with z-gradient facilities. 1H and 13C chemical shifts
are given relative to TMS. Unless otherwise specified, spectra were
recorded at 25 ꢁC. Mass spectra were run on a Thermo Mat900XP
for EI and a Waters Micromaldi for TOF. Melting points were de-
termined on a Sanyo-Gallenkamp capillary melting point apparatus
and are uncorrected.
4.2.4. N-Benzyl-N-(4-chlorophenyl)-3-phenylacrylamide
(2e). Following the general procedure, N-(4-chlorophenyl)-3-
phenylacrylamide15 1e (1.3 g, 5.0 mmol) was converted to 2e
(1.5 g, 88%) as a white solid; Rf (DCM) 0.4; mp 105e107 ꢁC; dH
(500 MHz, CDCl3) 5.01 (2H, s), 6.30 (1H, d, J 15.4 Hz), 7.00 (2H, d, J
8.3 Hz), 7.20e7.35 (12H, m), 7.76 (1H, d, J 15.4 Hz); dC (125 MHz,
CDCl3) 53.3 (CH2), 118.4 (CH), 127.6 (CH), 128.0 (CH), 128.6 (CH),
128.8 (CH), 128.8 (CH), 129.8 (CH), 129.9 (CH), 133.7 (C), 135.0 (C),
137.2 (C), 140.6 (C), 143.0 (CH), 165.9 (C); nmax (solid) 1651, 1606,
1587, 1488, 1448, 1422, 1388, 1357, 1332, 1238, 1216, 1091, 1079,
1016, 1007, 850, 760, 731, 725, 696, 684 cmꢀ1; m/z (EI) 349 (33, Mþ),
347 (100, Mþ), 219 (18), 217 (55), 131 (80%); HMRS (EI): Mþ, found
347.1072. C22H18ClNO requires 347.1071.
4.2. General procedure for the synthesis of the N-
benzylcinnamanilides
The appropriate cinnamanilide (5.0 mmol), benzyl bromide
(0.60 mL, 5.0 mmol) and KtBuO (0.55 g, 5.0 mmol) in THF (100 mL)
were stirred and heated under reflux for 1 h. On cooling, the THF
was removed by rotary evaporation and the residue partitioned
between H2O (50 mL) and EtOAc (100 mL). The EtOAc was sepa-
rated, washed with brine (50 mL) and dried (MgSO4). Removal of
the solvent gave the crude N-benzylcinnamanilide, which was ei-
ther recrystallised from EtOAc/petrol, or purified by column chro-
matography on Al2O3, eluting with a solvent gradient from 1:1
DCM/petrol to DCM, then recrystallised as before.
4.2.5. N-Benzyl-N-(4-fluorophenyl)-3-phenylacrylamide
(2f). Following the general procedure, N-(4-fluorophenyl)-3-
phenylacrylamide16 1f (1.2 g, 5 mmol) was converted to 2f
(1.45 g, 87% yield) as a white solid; Rf (DCM) 0.3; mp 94e95 ꢁC; dH
(500 MHz, CDCl3) 5.00 (2H, s), 6.27 (1H, d, J 15.5 Hz), 6.98e7.05 (4H,
m), 7.20e7.30 (10H, m), 7.74 (1H, d, J 15.5 Hz); dC (125 MHz, CDCl3)
53.4 (CH2), 116.5 (CH, d, J 22 Hz), 118.4 (CH), 127.6 (CH), 127.9 (CH),
128.6 (CH), 128.8 (CH), 128.9 (CH), 129.8 (CH), 130.3 (CH, d, J 8 Hz),
135.1 (C), 137.3 (C), 138.0 (C), 142.8 (CH), 161.8 (C, d, J 250 Hz), 166.1
(C); nmax (solid) 1659, 1613, 1504, 1385, 1355, 1335, 1215, 1151, 980,
848, 765, 721, 684, 603, 559, 489, 456 cmꢀ1; m/z (EI) 331 (58, Mþ),
201 (35), 131 (100), 103 (39%); HMRS (EI): Mþ, found 332.1441.
C22H19FNO requires 332.1445.
4.2.1. N-Benzyl-N-(4-nitrophenyl)-3-phenylacrylamide (2b). Following
the general procedure, N-(4-nitrophenyl)-3-phenylacrylamide7 1b
(1.4 g, 5 mmol) was converted to 2b (1.6 g, 87%) as a white solid; Rf
(70% EtOAc/petrol) 0.6; mp 108e110 ꢁC; dH (500 MHz, CDCl3) 5.11 (2H,
s), 6.33 (1H, d, J 15.4 Hz), 7.20e7.38 (12H, m), 7.81 (1H, d, J 15.4 Hz),
4.2.6. N-Benzyl-N-(3,4-dichlorophenyl)-3-phenylacrylamide
(2g). Following the general procedure, N-(3,4-dichlorophenyl)-3-
phenylacrylamide17 1g (2.0 g, 7.5 mmol) was converted to 2g
(2.4 g, 84% yield) as a white solid; Rf (DCM) 0.5; mp 110e112 ꢁC; dH
(500 MHz, CDCl3) 5.00 (2H, s), 6.31 (1H, d, J 15.4 Hz), 6.89 (1H, dd, J
2.0, 8.4 Hz), 7.19e7.38 (11H, m), 7.41 (1H, d, J 8.4 Hz), 7.79 (1H, d, J
8.22 (2H, dd, J 1.9, 8.9 Hz); dC (125 MHz, CDCl3) d 53.2 (CH2), 117.9 (CH),
124.9 (CH), 127.9 (CH), 128.1 (CH), 128.3 (CH), 128.6 (CH), 128.8 (CH),
128.9 (CH), 130.2 (CH), 134.7 (C), 136.8 (C), 144.1 (CH), 146.5 (C), 148.2
(C), 165.8 (C); nmax (solid) 1653, 1605, 1590, 1520, 1494, 1333, 1213,
1196, 1031, 1007, 859, 760, 730, 699, 684 cmꢀ1; m/z (EI) 358 (100, Mþ),

8596
F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
15.4 Hz); dC (125 MHz, CDCl3) 53.3 (CH2), 117.9 (CH), 127.8 (CH),
128.1 (CH),128.1 (CH),128.7 (CH),128.7 (CH),128.9 (CH),130.0 (CH),
130.1 (CH), 131.1 (CH), 132.2 (C), 133.4 (C), 134.9 (C), 136.9 (C), 141.6
(C), 143.7 (CH), 165.8 (C); nmax (solid) 1650, 1611, 1470, 1389, 1379,
1327, 1237, 1197, 1134, 1081, 1033, 982, 882, 872, 823, 758, 716, 696,
683 cmꢀ1; m/z (EI) 383 (16, Mþ), 381 (25, Mþ), 131 (18), 86 (63), 84
(100%); HMRS (EI) Mþ, 381.0678. C22H17Cl2NO requires 381.0682.
7.16 (1H, ddd, J 1.3, 7.7, 8.0 Hz), 7.2e7.39 (11H, m), 7.78 (1H, d, J
15.4 Hz); dC (CDCl3) 52.33 (CH2), 116.90 (CH, d, J 20 Hz), 117.9 (CH),
124.7 (CH, d, J 4 Hz), 127.5 (CH), 128.0 (CH), 128.4 (CH), 128.8 (CH),
129.0 (CH),129.3 (C, d, J 13 Hz),129.8 (CH),130.0 (CH, d, J 8 Hz),131.1
(CH), 135.1 (C), 137.1 (C), 143.2 (CH), 158.3 (C, d, J 250 Hz), 166.2 (C);
nmax (solid) 1651, 1614, 1606, 1496, 1387, 1330,1226, 1215, 1191, 1107,
1079, 980, 861, 818, 763, 733, 699, 679 cmꢀ1; m/z (EI) 331 (34, Mþ),
201 (38), 131 (100), 103 (36), 91 (20%); HMRS (EI) Mþ, found
331.1365. C22H18FNO requires 331.1367.
4.2.7. N-Benzyl-N-(4-aminophenyl)-3-pheny-acrylamide
(2h). Following the procedure of Bellamy et al.18 a stirred solution
of 2b (0.66 g, 1.8 mmol) in EtOH (5 mL) and tin (II) chloride (1.0 g,
4.7 mmol) was heated under reflux for 3 h. The reaction mixture
was basified with an excess of satd aqueous NaHCO3 solution
and filtered through Celite. The Celite was washed with EtOAc
(3ꢂ50 mL), each washing used to extract the product from the
aqueous filtrate. The organic extracts were dried (MgSO4), filtered
and concentrated in vacuo. The residue was recrystallised from
CHCl3/petrol to give the title compound 2h (0.54 g, 90%) as a light
grey solid; mp 169e170 ꢁC; dH (500 MHz, CDCl3) 3.77 (2H, br s), 4.96
(2H, s), 6.39 (1H, d, J 15.6 Hz), 6.61 (2H, dm, J 8.6 Hz), 6.80 (2H, dm, J
8.6 Hz), 7.20e7.35 (10H, m), 7.71 (1H, d, J 15.6 Hz); dC (125 MHz,
CDCl3) 53.4 (CH2), 115.6 (CH), 119.1 (CH), 127.3 (CH), 127.9 (CH),
128.4 (CH), 128.7 (CH), 128.9 (CH), 129.4 (CH), 129.5 (CH), 132.7 (C),
137.8 (C), 141.9 (CH), 146.0 (C), 166.5 (C); nmax (solid) 3458, 3313,
3210, 1643, 1591, 1578, 1514, 1493, 1401, 1299, 1282, 1238, 1196,
1080, 978, 824, 763, 728, 700, 680 cmꢀ1; m/z (EI) 328 (100, Mþ), 198
(58), 197 (18), 86 (18), 84 (29%); HMRS (EI) Mþ, found 328.1573.
C22H20N2O requires 328.1570.
4.2.11. N-Benzyl-N-(2-bromophenyl)-3-phenylacrylamide
(2l). Following the general procedure, N-(2-bromophenyl)-3-
phenylacrylamide20 1l (1.5 g, 5.0 mmol) was converted to 2l
(1.6 g, 89%) as a white solid; mp 115e117 ꢁC; dH (500 MHz, CDCl3)
4.21 (1H, d, J 14.3 Hz), 5.72 (1H, d, J 14.3 Hz), 6.10 (1H, d, J 15.4 Hz),
6.86 (1H, dm, J 7.4 Hz), 7.29e7.31 (12H, m), 7.72 (1H, dm, J 7.1 Hz),
7.78 (1H, d, J 15.4 Hz); dC (125 MHz, CDCl3) 51.8 (CH2), 118.1 (CH),
124.2 (C), 127.6 (CH), 128.0 (CH), 128.4 (CH), 128 (CH), 128.7 (CH),
129.5 (CH), 129.7 (CH), 129.9 (CH), 131.9 (CH), 134.0 (CH), 135.2 (C),
137.1 (C), 140.4 (C), 143.1 (CH), 165.9 (C); nmax (solid) 1656, 1614,
1473, 1392, 1331, 1243, 1209, 977, 774, 761, 728, 700, 680, 629, 564,
483, 455, 440 cmꢀ1; m/z (EI) 393 (44, Mþ), 391 (45, Mþ), 312 (77),
131 (58), 86 (64), 84 (100%); HMRS (EI) Mþ, found 391.0563.
C22H18BrNO requires 391.0567.
4.2.12. N-Benzyl-N-(2-methylphenyl)-3-phenylacrylamide
(2m). Following the general procedure, N-(2-methylphenyl)-3-
phenylacrylamide21 1m (1.8 g, 7.5 mmol) was converted to 2m
(2.1 g, 85% yield) as a white solid; Rf (Et2O) 0.8; mp 81e82 ꢁC; dH
(500 MHz, CDCl3) 2.04 (3H, s), 4.55 (1H, d, J 13.9 Hz), 5.32 (1H, d, J
13.9 Hz), 6.17 (1H, d, J 15.5 Hz), 6.86 (1H, d, J 7.8 Hz), 7.12e7.20 (1H,
m), 7.20e7.30 (12H, m), 7.77 (1H, d, J 15.5 Hz); dC (125 MHz, CDCl3)
17.7 (CH3) 52.5 (CH2), 118.2 (CH), 127.1 (CH), 127.6 (CH), 127.9 (CH),
128.4 (CH),128.5 (CH),128.7 (CH),129.5 (CH),129.6 (CH),131.4 (CH),
135.2 (C), 136.6 (C), 137.3 (C), 140.4 (C), 142.8 (CH), 166.1 (C); nmax
(solid) 1651, 1612, 1490, 1394, 1360, 1330, 1242, 1216, 1017, 973, 778,
759, 727, 699, 679, 632, 566, 484, 461, 415 cmꢀ1; m/z (EI) 327 (85,
Mþ), 197 (18), 131 (32), 86 (63), 84 (100%); HMRS (EI) Mþ, found
327.1610. C23H21NO requires 327.1618.
4.2.8. N-Benzyl-N-(3-aminophenyl)-3-phenylacrylamide
(2i). Following the procedure described for 2h; 2c (3.9 g, 11 mmol)
was converted into the title compound 2i (3.25 g, 90%) as a light
grey solid; mp 131e132 ꢁC; dH (500 MHz, CDCl3) 3.60 (br s, 2H), 4.99
(2H, s), 6.38 (1H, t, J 2.0 Hz), 6.43 (1H, d, J 15.5 Hz), 6.50 (1H, d, J
7.7 Hz), 6.63 (dm, J 7.3 Hz), 7.11 (1H, t, J 7.9 Hz), 7.20e7.33 (8H, m),
7.73 (1H, d, J 15.5 Hz); dC (125 MHz, CDCl3) 53.3 (CH2), 114.5 (CH),
114.6 (CH), 118.5 (CH), 119.1 (CH), 127.3 (CH), 128.0 (CH), 128.4 (CH),
128.7 (CH), 128.7 (CH), 129.5 (CH), 130.2 (CH), 135.4 (C), 137.8 (C),
142.0 (CH), 143.2 (C), 147.5 (C), 166.0 (C); nmax (solid) 3456, 3351,
1644, 1592, 1583, 1492, 1394, 1238, 1201, 1160, 1040, 996, 981, 856,
773, 762, 723, 700 cmꢀ1; m/z (EI) 328 (49, Mþ), 251 (38), 237 (66),
198 (100), 197 (56), 131 (71), 103 (36), 91 (21%); HMRS (EI) Mþ,
found 328.1567. C22H20N2O requires 328.1570.
4.2.13. N-Benzyl-N-(2-methoxyphenyl)-3-phenylacrylamide
(2n). Following the general procedure, N-(2-methoxyphenyl)-3-
phenylacrylamide22 1n (1.3 g, 5.0 mmol) was converted to 2n
(1.7 g, 85%) as a colourless oil; Rf (Et2O) 0.7; dH (500 MHz, CDCl3)
3.73 (3H, s), 4.46 (1H, d, J 14.3 Hz), 5.44 (1H, d, J 14.3 Hz), 6.27 (1H,
d, J 15.5 Hz), 6.85e6.90 (2H, m), 6.95 (1H, d, J 8.2 Hz), 7.17e7.34
(11H, m), 7.73 (1H, d, J 15.5 Hz); dC (125 MHz, CDCl3) 51.9 (CH2),
55.6 (CH3), 112.0 (CH), 118.8 (CH), 120.8 (CH), 127.2 (CH), 127.9
(CH), 128.2 (CH), 128.7 (CH), 129.1 (CH), 129.4 (CH), 129.6 (CH),
130.2 (C); 130.7 (CH), 135.5 (C), 137.8 (C); 142.0 (CH), 155.5 (C);
166.6 (C); nmax (film) 1652, 1615, 1495, 1384, 1253, 1196, 1023,
749, 697, 627, 563 cmꢀ1; m/z (EI) 343 (25, Mþ), 213 (85), 131 (100),
103 (38%); HMRS (EI) Mþ, found 343.1569. C23H21NO2 requires
343.1567.
4.2.9. N-Benzyl-N-(2-chlorophenyl)-3-phenylacrylamide
(2j). Following the general procedure, N-(2-chlorophenyl)-3-
phenylacrylamide15 1j (1.3 g, 5 mmol) was converted to 2j (1.5 g,
86%) as a white solid; Rf (DCM) 0.3; mp 102e104 ꢁC; dH (500 MHz,
CDCl3) 4.28 (1H, d, J 14.3 Hz), 5.67 (1H, d, J 14.3 Hz), 6.13 (1H, d, J
15.4 Hz), 5.89 (1H, dd, J 7.8, 1.4 Hz), 7.18 (1H, dt, J 1.4, 7.7 Hz),
7.21e7.30 (5H, m), 7.32 (1H, dt, J 1.4, 7.7 Hz), 7.52 (1H, dd, J 1.4,
7.8 Hz), 7.78 (1H, d, J 15.4 Hz); dC (125 MHz, CDCl3) 51.8 (CH2), 118.0
(CH), 127.6 (CH), 127.7 (CH), 128.0 (CH), 128.4 (CH), 128.7 (CH), 129.4
(CH), 129.7 (CH), 130.7 (CH), 131.7 (CH), 133.6 (C), 135.1 (CH), 137.1
(C), 138.9 (C), 143.2 (CH), 166.0 (C); nmax (solid) 1655, 1615, 1478,
1390, 1361, 1332,1244, 1211, 1072, 1016, 978, 775, 761, 743, 733, 698,
680 cmꢀ1; m/z (EI) 349 (7, Mþ), 347 (21, Mþ), 312 (20) 217 (20), 131
(100), 103 (33), 91 (21%); HMRS (EI) Mþ, found 347.1069.
C22H18ClNO requires 347.1071.
4.2.14. N-4-Methyl-benzyl-N-(4-chlorophenyl)-3-phenylacrylamide
(2o). Following the general procedure, N-(4-chlorophenyl)-3-
phenylacrylamide15 1e (1.3 g, 5.0 mmol) was converted to 2o
(1.6 g, 88%), Rf (DCM) 0.3; mp 139e141 ꢁC; dH (500 MHz, CDCl3) 2.31
(3H, s), 4.97 (2H, s), 6.29 (1H, br d, J 15.4 Hz), 6.99 (2H, d, J 8.5 Hz),
7.08 (2H, d, J 8.0 Hz), 7.12 (2H, d, J 8.0 Hz), 7.28e7.35 (7H, m), 7.75
(1H, d, J 15.4 Hz); dC (125 MHz, CDCl3) 21.2 (CH3), 53.0 (CH2), 118.5
(CH), 128.0 (CH), 128.8 (CH), 128.8 (CH), 129.3 (CH), 129.7 (CH),
129.8 (CH), 133.7 (C), 134.2 (C), 135.1 (C), 137.2 (C), 140.7 (C), 142.9
(CH),165.9 (C); nmax (solid) 1649,1608,1492, 1380, 1325, 1205, 1092,
1034, 1013, 973, 839, 763, 570, 519, 477 cmꢀ1; m/z (EI) 363 (15, Mþ),
4.2.10. N-Benzyl-N-(2-fluorophenyl)-3-phenylacrylamide
(2k). Following the general procedure, N-(2-fluorophenyl)-3-
phenylacrylamide19 1k (1.8 g, 7.5 mmol) was converted to 2k
(2.0 g, 80%) as a white solid; Rf (DCM) 0.3; mp 74e75 ꢁC; dH
(500 MHz, CDCl3) 4.60 (1H, d, J 14.4 Hz), 5.42 (1H, d, J 14.4 Hz), 6.28
(1H, d, J 15.4 Hz), 6.98 (1H, dt, J 1.5, 7.7 Hz), 7.09 (1H, dt, J 0.7, 8.0 Hz),

F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
8597
361 (42, Mþ), 233 (12), 231 (38), 131 (100), 107 (63), 105 (59%);
HMRS (CI) MHþ362.1291. C23H21ClNO requires 362.1306.
5.35 (0.5H, d, J 16.0 Hz), 6.87e6.92 (1H, m), 7.04e7.09 (1.5H, m),
7.11e7.15 (1H, m), 7.17e7.43 (9.5H, m); dC (125 MHz, CDCl3) 37.3
(CH), 38.5 (CH2), 38.7 (CH2), 41.5 (CH), 45.9 (CH2), 46.1 (CH2), 112.7
(CH), 119.9 (CH, q, J 3.8 Hz), 120.0 (CH), 120.9 (CH, q, J 5.8 Hz), 127.0
(C), 127.0 (CH), 127.0 (C), 127.1 (CH), 127.4 (CH), 127.6 (CH), 127.6
(CH),127.8 (CH),128.3 (CH),128.7 (CH),128.8 (CH),129.0 (CH),129.2
(CH), 130.2 (C), 130.5 (C), 133.1 (C), 136.2 (C), 136.2 (C), 139.9 (C),
140.0 (C), 140.1 (C), 141.5 (C), 168.5 (C), 169.1 (C); nmax (film)
1677, 1437, 1309, 1262, 1166, 1117, 925, 715, 693 cmꢀ1; m/z (EI) 381
(100, Mþ); HRMS (CI) MHþ, found 381.1335. C23H18F3NO requires
381.1335. Further elution with DCM gave 2-(3-trifluormethyl
phenyl)-5-phenyl-1,2,4,5-tetrahydro-2-benzazepin-3-one 4d (0.50
g, 65%) as a white solid; mp 129e130 ꢁC; dH (500 MHz, CDCl3) 3.21
(1H, dd, J 4.7, 13.7 Hz), 3.45 (1H, dd, J 10.9, 13.7 Hz), 4.67 (1H, dd, J
4.7, 10.9 Hz), 4.73 (1H, d, J 16.5 Hz), 5.40 (1H, d, J 16.5 Hz), 7.05 (1H,
d, J 7.3 Hz), 7.10e7.19 (3H, m), 7.19e7.26 (3H, m), 7.29e7.33 (2H, m),
7.38e7.42 (1H, m), 7.43e7.51 (3H, m); dC (125 MHz, CDCl3) 43.2
(CH2), 45.8 (CH), 56.2 (CH2), 122.6 (CH, q, J 3.8 Hz), 123.3 (CH, q, J
3.6 Hz), 126.9 (CH), 128.3 (CH), 128.8 (CH), 128.9 (CH), 129.2 (CH),
129.6 (CH),131.5 (C, q, J 33 Hz), 133.0 (CH), 134.7 (C), 140.2 (C), 143.6
(C),146.0 (C), 171.5 (C); nmax (solid) 1657, 1454,1323,1123, 1072, 901,
759, 699, 562 cmꢀ1; m/z (EI) 381 (13, Mþ), 262 (16), 219 (31), 193
(27),192 (45),191 (22),179 (60),178 (100),115 (20%); HMRS (EI) Mþ,
found 381.1335. C23H18F3NO requires 381.1335.
4.2.15. N-3-Methyl-benzyl-N-(4-chlorophenyl)-3-phenylacrylamide
(2p). Following the general procedure, N-(4-chlorophenyl)-3-
phenylacrylamide15 1e (1.3 g, 5.0 mmol) was converted to 2p
(1.5 g, 83%), Rf (DCM) 0.3; mp 86e88 ꢁC; dH (500 MHz, CDCl3) 2.31
(3H, s), 4.98 (2H, s), 6.31 (1H, d, J 15.4 Hz), 6.98e7.02 (3H, m),
7.04e7.08 (2H, m), 7.16 (1H, t, J 7.5 Hz), 7.28e7.35 (7H, m); dC
(125 MHz, CDCl3) 21.5 (CH3), 53.2 (CH2), 118.4 (CH), 125.7 (CH),
128.0 (CH), 128.4 (CH), 128.4 (CH), 128.8 (CH), 129.4 (CH), 129.7
(CH), 129.8 (CH), 133.7 (C), 135.1 (C), 137.2 (C), 138.3 (C), 140.7 (C),
142.9 (CH), 165.9 (C); nmax (solid) 1652, 1611, 1491, 1378, 1323, 1210,
1091, 1034, 1012, 976, 859, 761, 747, 724, 702, 683, 563, 522,
486 cmꢀ1; m/z (EI) 363 (11, Mþ), 361 (33, Mþ), 231 (36), 149 (27),
131 (100), 129 (26), 111 (30), 105 (44), 103 (52%); HMRS (EI) Mþ,
found 361.1229. C23H20ClNO requires 361.1228.
4.2.16. N-3,5-Dimethyl-benzyl-N-(4-chlorophenyl)-3-phenylacrylamide
(2q). Following the general procedure, N-(4-chlorophenyl)-3-phenyl
acrylamide15 1e (1.3 g, 5.0 mmol) was converted to 2q (1.6 g, 88%),
Rf (DCM) 0.4; mp 112e113 ꢁC; dH (500 MHz, CDCl3) 2.26 (6H, s), 4.94
(2H, s), 6.32 (1H, d, J 15.4 Hz), 6.84 (2H, s), 6.88 (1H, s), 7.01 (2H, d, J
8.3 Hz), 7.28e7.36 (7H, m), 7.77 (1H, d, J 15.4 Hz); dC (125 MHz, CDCl3)
21.3 (CH3), 53.2 (CH2), 118.5 (CH), 126.4 (CH), 128.0 (CH), 128.8 (CH),
129.2 (CH), 129.7 (CH), 129.8 (CH), 133.6 (C), 135.1 (C), 137.2 (C), 138.1
(C), 140.8 (C), 142.9 (CH), 165.9 (C); nmax (solid) 1650, 1614, 1490, 1383,
1318, 1281, 1242, 1199, 1089, 1030, 1011, 847, 763, 732, 700, 680, 563,
541, 521 cmꢀ1; m/z (EI) 377 (16, Mþ), 375 (44, Mþ), 247 (18), 245 (56),
131 (100), 119 (44), 103 (41%); HRMS (EI) Mþ, found 375.1385.
C24H22ClNO requires 375.1384.
4.3.4. Reaction of N-benzyl-N-(4-chlorophenyl)-3-phenylacrylamide
(2e) with TfOH. Following the general procedure, 2e (0.70
g, 2.0 mmol) was heated for 1 h in CHCl3. TLC showed the pres-
ence of two major products (Rf 0.7, 0.4 Et2O). Purification by col-
umn chromatography on SiO2, eluting with 3:1 DCM/petrol
gave 1-benzyl-6-chloro-4-phenyl-3,4-dihydro-1H-quinolin-2-one
3e (0.55 g, 78%) as an oil; dH (500 MHz, CDCl3) 3.05 (1H, dd, J
5.9, 15.7 Hz), 3.15 (1H, dd, J 8.0, 15.7 Hz), 4.28 (1H, dd, J 5.9, 8.0 Hz),
5.12 (1H, d, J 16.1 Hz), 5.35 (1H, d, J 16.1 Hz), 6.91 (1H, d, J 8.7 Hz),
6.95 (1H, dd, J 0.5, 2.3 Hz), 7.11 (1H, dd, J 2.3, 8.7 Hz), 7.14e7.21
(4H, m), 7.26 (1H, d, J 7.2 Hz), 7.28e7.39 (5H, m); dC (125 MHz,
CDCl3) 38.7 (CH2), 41.4 (CH), 46.0 (CH2), 117.2 (CH), 126.8 (CH),
127.4 (CH), 127.6 (CH), 127.9 (CH), 127.9 (CH), 128.4 (CH), 128.5 (C),
128.9 (CH), 129.1 (CH), 131.2 (C), 136.5 (C), 138.2 (C), 140.2 (C),
169.2 (C); nmax (film) 1670, 1488, 1452, 1417, 1366, 880, 810, 726,
694, 526 cmꢀ1; m/z (EI) 349 (27, Mþ), 348 (19), 347 (100% Mþ);
HRMS (CI) Mþ, 347.1070. C22H18ClNO requires 347.1071. Further
elution with DCM gave 2-(4-chlorophenyl)-5-phenyl-1,2,4,5-
tetrahydro-2-benzazepin-3-one 4e (0.13 g, 18%) as a white solid;
mp 173e174 ꢁC; dH (500 MHz, CDCl3) 3.10 (1H, dd, J 4.9, 13.7 Hz),
3.43 (1H, dd, J 11.2, 13.6 Hz), 4.61e4.70 (2H, m), 5.37 (1H, d, J
16.4 Hz), 7.03 (1H, d, J 7.3 Hz), 7.10e7.31 (12H, m); dC (125 MHz,
CDCl3) 43.3 (CH2), 45.8 (CH), 56.4 (CH2), 126.8 (CH), 126.9 (CH),
127.1 (CH), 128.3 (CH), 128.7 (CH), 128.9 (CH), 129.2 (CH), 132.1
(CH), 133.0 (C), 134.9 (C), 140.2 (C), 141.7 (C), 146.2 (C), 171.5 (C);
nmax (solid) 1654, 1489, 1446, 1417, 1085, 832, 734, 698, 664,
529 cmꢀ1; m/z (EI) 347 (10, Mþ), 219 (19), 192 (18), 179 (31), 178
(100), 115 (12%); HMRS (EI) Mþ, found 347.1069. C22H18ClNO re-
quires 347.1071.
4.3. General procedure for the TfOH-mediated cyclisation
Triflic acid (10 fold excess) was added to a stirred solution of the
cinnamanilide in CHCl3 (1 mmol/10 mL) or ClCH2CH2Cl (DCE)
(1 mmol/10 mL) and the reaction mixture was heated under gentle
reflux until no starting material was present by TLC. The reaction
mixture was cooled to room temperature, water (20 mL) was
added, followed by solid K2CO3 until CO2 evolution ceased. The
product was extracted into EtOAc (3ꢂ50 mL), dried (MgSO4), con-
centrated in vacuo and the product purified by column chroma-
tography on SiO2 and/or Al2O3.
4.3.1. Reaction of N-benzyl-N-(4-nitrophenyl)-3-phenylacrylamide
(2b) with TfOH. Following the general procedure, 2b (0.36 g,
2.0 mmol) was heated for 1 h in CHCl3, after which time no 2b
remained. TLC showed the presence of a single product (Rf 0.7
DCM), which proved to be 4-nitrobenzyl aniline (0.44 g, 96%); 1H
NMR (CDCl3) identical to the literature.23
4.3.2. Reaction of N-benzyl-N-(3-nitrophenyl)-3-phenylacrylamide
(2c) with TfOH. Following the general procedure, 2c (0.36 g,
1.0 mmol) was heated for 2 h in DCE. TLC showed the presence of
a single product (Rf 0.2, Et2O), which proved to be 3-nitrobenzyl
aniline (0.20 g, 87%); 1H NMR (CDCl3) identical to the literature.24
4.3.5. Reaction of N-benzyl-N-(4-fluorophenyl)-3-phenylacrylamide
(2f) with TfOH. Following the general procedure, 2f (0.99 g,
3.0 mmol) was heated with TfOH (3 mL, 30 mmol) for 3 h in CHCl3.
TLC showed the presence of two major products (Rf 0.4, 0.1, 1:1
DCM/Et2O). Purification by column chromatography on SiO2, elut-
ing with 3:1 DCM/petrol gave 1-benzyl-6-fluoro-4-phenyl-3,4-
dihydro-1H-quinolin-2-one (3f) (0.66 g, 67%) as a white solid; mp
70e72 ꢁC; dH (500 MHz, CDCl3) 3.05 (1H, dd, J 5.7, 15.7 Hz), 3.13 (1H,
dd, J 8.8, 15.7 Hz), 4.22 (1H, dd, J 5.7, 8.8 Hz), 5.07 (1H, d, J 16.1 Hz),
5.31 (1H, d, J 16.1 Hz), 6.65 (1H, dd, J 2.5, 8.8 Hz), 6.83 (1H, dt, J 2.9,
8.1 Hz), 6.91 (1H, dd, J 4.9, 9.0 Hz), 7.13e7.20 (4H, m), 7.21e7.38 (6H,
4.3.3. Reaction of N-benzyl-N-(3-trifluoromethylphenyl)-3-phenyl
acrylamide (2d) with TfOH. Following the general procedure, 2d
(0.36 g, 2.0 mmol) was heated for 4 h in CHCl3. TLC showed
the presence of two major products (Rf 0.8, 0.4 Et2O). Purification
by column chromatography on SiO2, eluting with 3:1 DCM/petrol
gave a 1:1 mixture of 5-trifluoromethyl- and 7-trifluoromethyl-1-
benzyl-4-phenyl-3,4-dihydro-1H-quinolin-2-one 3d as an oil (0.15
g, 20%); dH (500 MHz, CDCl3) 3.08e3.24 (2H, m), 4.34 (0.5H, t, J
7.0 Hz), 4.71 (0.5H, d, J 3.6 Hz), 5.10 (0.5H, d, J 16.0 Hz), 5.16 (1H, s),

8598
F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
m); dC (125 MHz, CDCl3) 38.7 (CH2), 41.6 (CH), 46.2 (CH2), 114.2 (CH,
d, J 23 Hz), 115.4 (CH, d, J 23 Hz), 117.1 (CH, d, J 8.2 Hz), 126.7 (CH),
127.3 (CH), 127.6 (CH), 127.9 (CH), 128.8 (CH), 129.1 (CH), 131.6 (C, d,
J 7.4 Hz),135.8 (C, d, J 3 Hz),136.7 (C).140.2 (C),158.7 (C, d, J 243 Hz),
169.1 (C); nmax (solid) 1668, 1492, 1427, 1376, 1324, 1271, 1205,
1152, 870, 814, 777, 725, 701, 569, 490 cmꢀ1; m/z (EI) 331 (100, Mþ),
212 (12%); HRMS (CI) MHþ, found 332.1430. C22H19FNO requires
332.1445. Further elution with DCM gave 2-(4-fluorophenyl)-5-
phenyl-1,2,4,5-tetrahydro-2-benzazepin-3-one (4f) (0.18 g, 18%),
mp 185e186 ꢁC; dH (500 MHz, CDCl3) 3.17 (1H, dd, J 5.0, 13.7 Hz),
3.45 (1H, dd, J 11.2, 13.7 Hz), 4.62 (1H, d, J 16.4 Hz), 4.67 (1H, dd, J
5.0, 11.2 Hz), 5.39 (1H, d, J 16.4 Hz), 7.00e7.06 (3H, m), 7.11e7.27
(8H, m), 7.31 (2H, t, J 7.3 Hz); dC (125 MHz, CDCl3) 43.3 (CH2), 45.9
(CH), 56.6 (CH2), 116.0 (CH, d, J 23 Hz), 126.8 (CH), 126.9 (CH), 127.6
(CH, d, J 8.4 Hz), 128.3 (CH), 128.7 (CH), 128.9 (CH), 128.9 (CH), 133.0
(CH), 135.0 (C), 139.3 (C), 140.3 (C), 146.3 (C), 161.0 (C, d, J 246 Hz),
171.6 (C); nmax (solid) 1665, 1505, 1436, 1396, 1203, 1157, 1098, 837,
782, 761, 741, 704, 535, 527, 504 cmꢀ1; m/z (EI) 331 (22, Mþ), 219
(24), 192 (25), 177 (41), 176 (100%), HMRS (EI) Mþ, found 331.1370.
C22H18FNO requires 331.1367.
dH (500 MHz, CDCl3) 3.14 (1H, dd, J 5.0, 13.7 Hz), 3.43 (1H, dd, J 11.3,
13.7 Hz), 3.62 (2H, br s), 4.57 (1H, d, J 16.3 Hz), 4.65 (1H, dd, J 5.0,
11.3 Hz), 5.35 (1H, d, J 16.3 Hz), 6.59 (2H, dm, J 8.6 Hz), 8.92 (2H, dm,
J 8.6 Hz), 7.01 (1H, d, J 7.3 Hz), 7.10 (1H, dd, J 1.2, 7.3 Hz), 7.12e7.36
(7H, m); dC (125 MHz, CDCl3) 43.3 (CH2), 45.9 (CH), 56.9 (CH2), 115.5
(CH),126.6 (CH),126.7 (CH),127.0 (CH),128.3 (CH),128.5 (CH),128.8
(CH), 129.0 (CH), 132.9 (CH), 134.4 (C), 135.4 (C), 140.3 (C), 145.5 (C),
146.5 (C), 171.8 (C); nmax (film) 3453, 3351, 1649, 1626, 1511, 1444,
1416, 1287, 832, 760, 747, 701, 530 cmꢀ1; m/z (EI) 329 (24, MHþ),
328 (100, Mþ), 219 (31), 192 (25), 191 (19), 179 (57), 178 (55), 165
(17), 150 (17), 115 (18), 108 (72%); HMRS (EI) Mþ, found 328.1570.
C22H20N2O requires 328.1571. A small sample was converted to the
HCl salt: mp 177e179 ꢁC.
4.3.8. Reaction of N-benzyl-N-(3-aminophenyl)-3-phenylacrylamide
(2i) with TfOH. Following the general procedure, 2i (0.66 g,
2.0 mmol) was heated for 8 h in CHCl3. TLC showed the presence of
two major products (Rf 0.5, 0.1, Et2O). Purification by column
chromatography on SiO2, eluting with DCMþ0.5% MeOH gave 3-
aminobenzylaniline (0.1 g, 25%), NMR identical to the litera-
ture.25 Further elution with DCMþ2% MeOH gave 2-(4-amino
phenyl)-5-phenyl-1,2,4,5-tetrahydro-2-benzazepin-3-one 4i (0.40
g, 61%) as an oil; dH (500 MHz, CDCl3) 3.15 (1H, dd, J 4.9, 13.7 Hz),
3.42 (1H, dd, J 11.1, 13.7 Hz), 3.66 (br s, 2H), 4.63 (1H, d, J 16.4 Hz),
4.65 (1H, dd, J 4.9, 11.1 Hz), 5.33 (1H, d, J 16.4 Hz), 6.50e6.56 (3H,
m), 7.01 (1H, dd, J 1.2, 7.1 Hz), 7.07e7.23 (9H, m), 7.30 (2H, t, J
7.7 Hz); dC (125 MHz, CDCl3) 43.4 (CH2), 45.9 (CH), 56.4 (CH2), 112.9
(CH), 113.7 (CH), 115.5 (CH), 126.7 (CH), 126.8 (CH), 128.4 (CH),
128.5 (CH), 128.9 (CH), 129.1 (CH), 129.9 (CH), 132.8 (CH), 135.2 (C),
140.3 (C), 144.3 (C), 146.4 (C), 147.5 (C), 171.5 (C); nmax (film) 3413,
3345, 3219, 1650, 1600, 1492, 1439, 1413, 1202, 727, 696 cmꢀ1; m/z
(EI) 329 (23, MHþ), 328 (100, MHþ), 219 (27), 192 (31), 179 (31), 178
(46), 108 (24%); HMRS (EI) Mþ, found 328.1561. C22H20N2O requires
328.1571. A small sample was converted to the HCl salt: mp
165e167 ꢁC.
4.3.6. Reaction of N-benzyl-N-(3,4-dichlorophenyl)-3-phenyl
acrylamide (2g) with TfOH. Following the general procedure, 2g
(0.77 g, 2.0 mmol) was heated for 2 h in DCE. TLC showed the
presence of two major products (Rf 0.7, 0.4, Et2O). Purification by
column chromatography on SiO2, eluting with 3:1 DCM/petrol
gave a 1:1 mixture of 5,6-dichloro- and 6,7-dichloro-1-benzyl-4-
phenyl-3,4-dihydro-1H-quinolin-2-one 3g as an oil (0.55 g, 71%);
dH (500 MHz, CDCl3) 3.0e3.21 (2H, m), 4.25 (0.5H, dd, J 5.9,
8.1 Hz), 4.79 (0.5H, dd, J 2.1, 6.3 Hz), 5.03 (0.5H, d, J 16.1 Hz), 5.12
(0.5H, d, J 1.1 Hz), 5.19 (0.5H, d, J 16.1 Hz), 5.29 (0.5H, d, J 16.1 Hz),
6.90 (0.5H, d, J 8.9 Hz), 6.99e7.03 (1.5H, m), 7.05e7.08 (1.5H, m),
7.12e7.19 (2.5H, m), 7.21e7.37 (6H, m); dC (125 MHz, CDCl3) 38.3
(CH2), 38.5 (CH2), 39.2 (CH), 41.1 (CH), 45.9 (CH2), 46.0 (CH2),
115.5 (CH), 117.7 (CH), 126.6 (C), 126.8 (CH), 127.0 (CH), 127.1 (CH),
127.5 (CH), 127.5 (CH), 127.6 (CH), 127.7 (C), 127.8 (CH), 128.5 (C),
128.8 (CH), 129.0 (CH), 129.2 (CH), 129.3 (CH), 129.6 (C), 129.8
(CH), 131.7 (C), 132.5 (C), 136.0 (C), 136.1 (C), 138.9 (C), 139.1 (C),
139.5 (C), 139.8 (C), 168.2 (C), 168.9 (C); nmax (film) 1677, 1583,
1400, 1362, 1144, 722, 693, 554 cmꢀ1; m/z (EI) 383 (35, Mþ), 382
(14), 381 (52, Mþ), 91 (100%); HRMS (CI) Mþ, found 381.0680.
C22H17Cl2NO requires 381.0682. Further elution with DCMþ1%
EtOAc gave 2-(3,4-dichlorophenyl)-5-phenyl-1,2,4,5-tetrahydro-
2-benzazepin-3-one 4g (0.12 g, 16%) as a white solid, mp
134e135 ꢁC; dH (500 MHz, CDCl3) 3.20 (1H, dd, J 4.9, 13.8 Hz), 3.41
(1H, dd, J 10.8, 13.8 Hz), 4.65 (1H, dd, J 4.9, 10.8 Hz), 4.68 (1H, d, J
16.5 Hz), 5.34 (1H, d, J 16.5 Hz), 7.02e7.05 (1H, m), 7.07 (1H, dd, J
2.5, 8.6 Hz), 7.10e7.13 (2H, m), 7.13e7.17 (1H, m), 7.17e7.27 (4H,
m), 7.28e7.33 (2H, m), 7.36 (1H, d, J 2.5 Hz), 7.40 (1H, d, J 8.6 Hz);
dC (500 MHz, CDCl3) 43.2 (CH2), 45.8 (CH), 56.2 (CH2), 125.2 (CH),
127.0 (CH), 127.8 (CH), 128.3 (CH), 128.9 (CH), 128.8 (CH), 128.9
(CH), 128.9 (CH), 130.4 (C), 130.6 (CH), 132.7 (C), 133.0 (CH), 134.6
(C), 140.1 (C), 142.4 (C), 146.0 (C), 171.5 (C); nmax (solid) 1662,
1470, 1440, 1415, 1336, 1132, 873, 749, 699, 520, 447 cmꢀ1; m/z
(EI) 383 (7, Mþ), 381 (10, Mþ), 219 (25), 179 (41), 178 (100),
115 (18%); HMRS (EI) Mþ, found 381.0673. C22H17Cl2NO requires
381.0682.
4.3.9. Reaction of N-benzyl-N-(2-chlorophenyl)-3-phenylacrylamide
(2j) with TfOH. Following the general procedure, 2j (0.70 g,
2.0 mmol) was heated for 18 h in CHCl3. TLC showed the presence of
only one major product (Rf 0.1 DCM; 0.7 Et2O). Purification by
column chromatography on SiO2, eluting with DCM gave 8-chloro-
4-phenyl-3,4-dihydro-1H-quinolin-2-one 5j (0.026 g, 5%) as
a white solid; mp 127e128 ꢁC; dH (500 MHz, CDCl3) 2.94 (2H, d, J
7.5 Hz), 4.32 (1H, t, J 7.5 Hz), 6.84 (1H, d, J 7.7 Hz), 6.90 (1H, t, J
7.8 Hz), 7.15e7.40 (6H, m), 7.91 (1H, br s); dC (125 MHz, CDCl3) 38.1
(CH2), 42.4 (CH), 119.9 (C), 123.5 (CH), 127.0 (CH), 127.6 (CH), 127.8
(CH), 128.2 (CH), 128.6 (C), 129.1 (CH), 133.9 (C), 140.7 (C), 169.3 (C);
nmax (solid) 1671, 1597, 1479, 1342, 1163, 908, 801, 765, 731, 701, 570,
515, 489, 468 cmꢀ1; m/z (EI) 259 (33, Mþ), 258 (19), 257 (100, Mþ),
230 (20), 229 (24), 228 (54), 222 (31), 214 (39), 180 (14), 152 (19),
151 (14%); HRMS (EI) Mþ, found 257.0602. C15H12ClNO requires
257.0606. Further elution with DCMþ2% EtOAc gave 2-(2-
chlorophenyl)-5-phenyl-1,2,4,5-tetrahydro-2-benzazepin-3-one 4j
(0.52 g, 74%); mp 132e133 ꢁC; dH (500 MHz, CDCl3) 3.01 (0.5H, dd, J
5.1, 13.3 Hz), 3.29e3.40 (0.5H, br m), 3.64 (0.5H, J 13.5 Hz), 4.19
(0.5H, d, J 16.3 Hz), 4.66e4.76 (2ꢂ 0.5H, m, including 4.70, dd, J 5.1,
12.9 Hz), 4.89 (0.5H, d, J 16.4 Hz), 4.95 (0.5H, d, J 16.4 Hz), 5.64
(0.5H, d, J 16.3 Hz), 6.98 (0.5H, d, J 7.5 Hz), 7.00e7.05 (1.5H, m),
7.10e7.34 (11.5H, m), 7.50 (0.5H, d, J 7.8 Hz); dC (500 MHz, CDCl3)
42.3 (CH2), 43.3 (CH2), 45.5 (CH), 46.0 (CH), 55.9 (CH2), 56.2 (CH2),
126.5 (CH),126.8 (CH), 127.8 (CH), 128.2 (CH), 128.4 (C), 128.5 (CH),
128.6 (CH), 128.7 (CH), 129.0 (CH), 129.1 (C), 129.3 (CH), 129.5 (C),
129.7 (CH), 130.5 (CH), 131.9 (C), 132.3 (CH), 132.5 (C), 132.9 (CH),
134.9 (C), 140.4 (C), 140.5 (C), 145.5 (C), 146.6 (C), 171.2 (C), 171.7 (C);
nmax (solid) 1666, 1480, 1437, 1415, 1345, 1221, 1034, 751, 741, 699,
676, 511 cmꢀ1; m/z (CI) 350 (35, MHþ), 348 (100, MHþ), 312 (74),
4.3.7. Reaction of N-benzyl-N-(4-aminophenyl)-3-phenylacrylamide
(2h) with TfOH. Following the general procedure, 2h (0.33 g,
1.0 mmol) was heated for 18 h in CHCl3. TLC showed the presence of
two major products (Rf 0.5, 0.1, Et2O). Purification by column
chromatography on SiO2, eluting with DCMþ0.5% MeOH gave
a product identified as 4-aminobenzyl aniline (0.02 g, 10%). Further
elution with DCMþ2% MeOH gave 2-(4-aminophenyl)-5-phenyl-
1,2,4,5-tetrahydro-2-benzazepin-3-one 4h as an oil (0.28 g, 85%);

F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
8599
179 (24%); HRMS (CI) MHþ, found 348.1146. C22H19ClNO requires
348.1150.
7.10e7.28 (6.23H, m), 7.28e7.35 (2.80H, m), 7.62 (0.33H, d, J
8.3 Hz), 7.68 (0.67H, dd, J 1.2, 8.0 Hz); dC (125 MHz, CDCl3) 42.3
(CH2), 43.6 (CH2), 45.4 (CH), 45.9 (CH), 55.9 (CH2), 56.2 (CH2), 122.3
(C), 122.8 (C), 126.5 (CH), 126.5 (CH), 126.8 (CH), 126.9 (CH), 128.1
(CH), 128.4 (CH), 128.5 (CH), 128.7 (CH), 128.7 (CH), 128.7 (CH),
129.0 (CH), 129.1 (CH), 129.2 (CH), 129.3 (CH), 129.3 (CH), 129.5
(CH), 129.8 (CH), 132.2 (CH), 132.9 (CH), 133.6 (CH), 133.7 (CH),
134.8 (C), 140.4 (C), 140.6 (C), 142.1 (C). 142.9 (C), 145.4 (C), 146.7
(C), 171.2 (C), 171.6 (C); nmax (solid) 1666, 1474, 1441, 1412, 1343,
1219, 1027, 755, 741, 698, 660, 505 cmꢀ1; m/z (EI), 312 (100), 179
(28), 178 (20%); (CI) 394 (80, MHþ), 392 (77, MHþ), 312 (100), 179
(51%); HRMS (CI) MHþ, found 392.0645. C22H19BrNO requires
392.0645.
Repeating the reaction, but heating under reflux for 5 h in CHCl3
gave, on elution with 1:3 petrol/DCM, a 4:1 ratio of an inseparable
mixture of 2l and 1-benzyl-8-bromo-4-phenyl-3,4-dihydro-1H-
quinolin-2-one 3l (0.24 g, 40%); dH (500 MHz, CDCl3) 2.84 (1H, dd, J
4.0, 14.9 Hz), 3.03 (1H, dd, J 10.7, 14.9 Hz), 4.02 (1H, dd, J 4.0,
10.7 Hz), 5.36 (1H, d, J 15.1 Hz), 5.58 (1H, d, J 15.1 Hz), 6.72 (1H, d, J
7.2 Hz), 6.84 (1H, t, J 7.7 Hz), 7.01e7.10 (4H, m), 7.10e7.71 (3H, m),
7.23e7.34 (3H, m), 7.46 (1H, d, J 7.7 Hz); dC (125 MHz, CDCl3) 39.4
(CH2), 42.1 (CH), 48.5 (CH2), 125.6 (CH), 126.9 (CH), 127.2 (CH), 127.5
(CH), 128.2 (CH), 128.3 (CH), 129.0 (CH), 133.8 (CH), 137.6 (C), 138.2
(C), 139.2 (C), 139.5 (C), 172.0 (C). Further elution as above gave 5l
(0.03 g, 6%) and 3k (0.30 g, 50%).
An authentic sample of 5j was prepared by the TfOH-mediated
cyclisation of N-(2-chlorophenyl)-3-phenylacrylamide 1j15 (0.52
g, 2 mmol) following the general procedure, heating under reflux in
CHCl3 for 5 h. Purification by column chromatography on SiO2,
eluting with DCMþ1% meOH gave 5j (0.21 g, 40%) identical to that
obtained above.
4.3.10. Reaction of N-benzyl-N-(2-fluorophenyl)-3-phenylacrylamide
(2k) with TfOH. Following the general procedure, 2k (0.66 g,
2.0 mmol) was heated for 5 h in CHCl3. TLC showed the presence of
only one major product (Rf 0.6, Et2O). Purification by column
chromatography on SiO2, eluting with DCM gave a product which,
from NMR, proved to be a mixture of compounds. Re-purification
by column chromatography on Al2O3 (basic, Brockman I), eluting
with 10% petrol/DCM gave 2-(2-fluorophenyl)-5-phenyl-1,2,4,5-
tetrahydro-2-benzazepin-3-one 4k (0.20 g, 30%) as a white solid;
mp 150e151 ꢁC; dH (500 MHz, CDCl3) 3.19 (1H, dd, J 4.9, 13.8 Hz),
3.47 (1H, dd, J 11.0, 13.8 Hz), 4.59 (1H, d, J 16.4 Hz), 4.68 (1H, dd, J
4.9, 11.0), 5.32 (1H, d, J 16.4 Hz), 7.00e7.32 (14H, m); dC (125 MHz,
CDCl3) 42.8 (CH2), 45.8 (CH), 56.4 (CH2),116.6 (CH),116.8 (CH),124.6
(CH), 124.6 (CH), 126.6 (CH), 126.8 (CH), 128.3 (CH), 128.5 (CH),
128.8 (CH), 128.9 (CH), 129.1 (CH), 130.6 (C), 130.7 (C), 132.7 (CH),
134.8 (C), 140.3 (C), 146.1 (C), 156.3 (C), 158.3 (C), 171.4 (C); nmax
(solid) 1671, 1510, 1441, 1402, 1344, 1268, 1234, 1209, 1102, 771, 759,
740, 700, 650, 513, 478, 444 cmꢀ1; m/z (EI) 331 (7, Mþ), 219 (27), 192
(31), 179 (36), 178 (100), 115 (21%), HMRS (EI) Mþ, found 331.1369.
C22H18FNO requires 331.1367. Further elution with 10% EtOAc/DCM
gave 8-fluoro-4-phenyl-3,4-dihydro-1H-quinolin-2-one 5k (0.24 g,
50%) as a white solid; mp 174e175 ꢁC; dH (500 MHz, CDCl3)
2.92e3.00 (2H, m), 4.33 (1H, t, J 7.5 Hz), 6.71 (1H, d, J 7.4 Hz),
6.86e6.92 (1H, m), 6.99e7.04 (1H, m), 7.18e7.23 (2H, m), 7.25e7.39
(3H, m); dC (125 MHz, CDCl3) 38.3 (CH2), 42.2 (CH), 114.2 (CH, d, J
18 Hz), 123.1 (CH, d, J 7.4 Hz), 123.7 (CH), 125.6 (C, d, J 11.3 Hz), 127.6
(CH), 127.8 (CH), 129.0 (C), 129.1 (CH), 140.9 (C), 149.9 (C, d, J
240 Hz),169.1 (C); nmax (solid) 1681,1496, 1359,1248,1110, 821, 765,
699, 661, 482 cmꢀ1; m/z (EI) 242 (17, MHþ), 241 (100, Mþ), 213 (24),
212 (72), 198 (48%); (CI) 242 (100, MHþ), 241 (72, Mþ), 212 (14),
164 (15%); HRMS (CI) MHþ, found 242.0967. C15H13FNO requires
242.0976.
4.3.12. 1-Benzyl-8-bromo-4-phenyl-3,4-dihydro-1H-quinolin-2-one
3l. Following the general procedure for N-benzylation, but heating
under reflux for 4 h, 5l (0.43 g, 1.8 mmol) was converted into 3l
(0.52 g, 94%); mp 123e125 ꢁC; dH (500 MHz, CDCl3) 2.84 (1H, dd, J
4.0, 14.9 Hz), 3.03 (1H, dd, J 10.7, 14.9 Hz), 4.02 (1H, dd, J 4.0,
10.7 Hz), 5.36 (1H, d, J 15.1 Hz), 5.58 (1H, d, J 15.1 Hz), 6.72 (1H, d, J
7.2 Hz), 6.84 (1H, t, J 7.7 Hz), 7.01e7.10 (4H, m), 7.10e7.71 (3H, m),
7.23e7.34 (3H, m), 7.46 (1H, d, J 7.7 Hz); dC (500 MHz, CDCl3) 39.4
(CH2), 42.1 (CH), 48.5 (CH2), 125.6 (CH), 126.9 (CH), 127.2 (CH), 127.5
(CH), 128.2 (CH), 128.3 (CH), 129.0 (CH), 133.8 (CH), 137.6 (C), 138.2
(C), 139.2 (C), 139.5 (C), 172.0 (C); nmax (solid) 1697, 1441, 1370, 1338,
1286, 1159, 771, 726, 704, 695, 572, 524, 489, 458 cmꢀ1; m/z (EI) 393
(100, Mþ), 391 (100, Mþ), 312 (43), 286 (70), 284 (60), 268 (37), 208
(36), 206 (42), 193 (37), 165 (44%); HRMS (EI) Mþ, 391.0569.
C22H18BrNO requires 391.0566.
4.3.11. Reaction of N-benzyl-N-(2-bromophenyl)-3-phenylacrylamide
(2l) with TfOH. Following the general procedure for cyclisation, 2l
(0.6 g, 1.5 mmol) was heated under reflux for 18 h in CHCl3. Puri-
fication by column chromatography on SiO2, eluting with 1:9
petrol/DCM gave 8-bromo-4-phenyl-3,4-dihydro-1H-quinolin-2-
one 5l (0.04 g, 8%) as a white solid; mp 117e118 ꢁC; dH
(500 MHz, CDCl3) 2.94 (2H, d, J 7.5 Hz), 4.31 (1H, t, J 7.5 Hz), 6.84
(1H, t, J 7.7 Hz), 6.88 (1H, dm, J 7.5 Hz), 7.16e7.20 (2H, m), 7.27e7.37
(3H, m), 7.43 (1H, dm, J 7.7 Hz), 7.90 (1H, br s); dC (125 MHz, CDCl3)
38.2 (CH2), 42.6 (CH), 110.0 (C), 124.0 (CH), 127.6 (CH), 127.8 (CH),
127.8 (CH), 129.1 (CH), 131.4 (CH), 135.0 (C), 140.7 (C), 169.4 (C);
nmax (solid) 1683, 1479, 1361, 1266, 1147, 801, 741, 725, 701, 632,
595, 546, 472 cmꢀ1; m/z (EI) 303 (98, Mþ), 301 (100, Mþ), 275 (27),
274 (42), 273 (24), 272 (41), 260 (30), 258 (31), 222 (43), 193 (27),
180 (22), 179 (20), 117 (17%); (CI) 304 (95, MHþ), 302 (100, MHþ),
226 (16), 224 (17), 222 (15%); HRMS (CI) MHþ, found 302.0167.
C15H13BrNO requires 302.0175. Further elution with DCM/1%
EtOAc gave 2-(2-bromophenyl)-5-phenyl-1,2,4,5-tetrahydro-2-
4.3.13. Reaction of N-benzyl-N-(2-methylphenyl)-3-phenyl
acrylamide (2m) with TfOH. Following the general procedure for
cyclisation, 2m (0.66 g, 2.0 mmol) was heated under reflux for 3 h
in CHCl3. TLC showed the presence of only one major product (Rf
0.5, Et2O). Purification by column chromatography on SiO2, eluting
with DCM gave 8-methyl-4-phenyl-3,4-dihydro-1H-quinolin-2-
one 5m (0.45 g, 95%) as a white solid; mp 123e125 ꢁC; dH
(500 MHz, CDCl3) 2.30 (3H, s), 2.94 (2H, dd, J 1.6, 7.3 Hz), 4.29 (1H, t,
J 7.3 Hz), 6.81 (1H, d, J 7.6 Hz), 6.89 (1H, dt, J 1.6, 7.6 Hz), 7.08 (1H, d, J
7.5 Hz), 7.16e7.36 (5H, m), 8.29 (1H, br s); dC (125 MHz, CDCl3) 17.2
(CH3), 38.4 (CH), 42.3 (CH2), 123.0 (CH), 123.5 (C), 126.3 (CH), 127.0
(C), 127.2 (CH), 127.9 (CH), 129.1 (CH), 129.6 (CH), 135.5 (C),141.6 (C),
170.6 (C); nmax (solid) 1671, 1470, 1368, 768, 731, 699, 490,
429 cmꢀ1; m/z (EI) 237 (100, Mþ), 222 (21), 208 (34), 194 (37), (CI)
239 (16%); (CI) 238 (100, MHþ), 237 (83), 160 (15%); HRMS (CI)
MHþ, found 238.1217. C16H16NO requires 238.1226.
4.3.14. Reaction of N-benzyl-N-(2-methoxyphenyl)-3-
phenylacrylamide (2n) with TfOH. Following the general pro-
cedure for cyclisation, 2n (1.0 g, 2.9 mmol) was heated under reflux
for 30 min in CHCl3. TLC showed the presence of only one major
product (Rf 0.5, Et2O). Purification by column chromatography on
SiO2, eluting with DCM gave 8-methoxy-4-phenyl-3,4-dihydro-1H-
quinolin-2-one 5n (0.43 g, 58%), mp 121e122 ꢁC; dH (500 MHz,
benzazepin-3-one 4l (0.50 g, 83%) as
a white solid; mp
124e125 ꢁC; dH (500 MHz, CDCl3) 2.99 (0.67H, dd, J 5.4, 13.8 Hz),
3.31 (0.33H, dd, J 9.1, 14.2 Hz), 3.37 (0.33H, dd, J 4.7, 14.2 Hz), 3.65
(0.67H, t, J 13.3 Hz), 4.11 (0.67H, d, J 16.3 Hz), 4.68 (0.67H, dd, J 5.4,
12.9 Hz), 4.74 (0.33H, dd, J 4.7, 9.1 Hz), 4.90 (0.67H, s), 5.68 (0.67H,
d, J 16.3 Hz), 6.93 (0.67H, dd, J 1.5, 7.7 Hz), 6.99e7.06 (2.30H, m),

8600
F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
CDCl3) 2.89 (1H, dd, J 8.3, 16.2 Hz), 2.94 (1H, dd, J 6.6, 16.2 Hz), 3.88
(3H, s), 4.29 (1H, t, J 7.4 Hz), 6.55 (1H, d, J 7.7 Hz), 6.80 (1H, d, J
7.7 Hz), 6.91 (1H, t, J 7.9 Hz), 7.17e7.21 (2H, m), 7.28 (1H, tt, J 2.1,
7.4 Hz), 7.30e7.35 (2H, m), 7.96 (1H, br s); dC (125 MHz, CDCl3) 38.4
(CH2), 42.2 (CH), 55.9 (CH3),109.4 (CH),120.4 (CH),122.9 (CH),126.5
(C), 127.1 (C), 127.3 (CH), 127.8 (CH), 128.2 (CH), 129.0 (CH), 141.6 (C),
146.0 (C), 169.3 (C); nmax (solid) 1681, 1493, 1449, 1416, 1373, 1260,
1097, 797, 740, 715, 702, 527, 491 cmꢀ1; m/z (EI) 253 (100, Mþ), 238
(10), 224 (14), 210 (21%), HMRS (EI) Mþ, found 253.1100. C16H15NO2
requires 253.1097.
at Rf 0.8 (Et2O) plus minor products at Rf 0.5 and 0.3. Purification by
column chromatography on SiO2, eluting with 1:3 petrol/DCM gave
1-(3-methylbenzyl)-6-choro-4-phenyl-3,4-dihydro-1H-quinolin-
2-one 3p (0.45 g, 62%); mp 113e114 ꢁC; dH (500 MHz, CDCl3) 2.30
(3H, s), 3.08 (1H, dd, J 5.9, 15.8 Hz), 3.15 (1H, dd, J 8.0, 15.8 Hz), 4.27
(1H, t, J 6.9 Hz), 5.01 (1H, d, J 16.1 Hz), 5.30 (1H, d, J 16.1 Hz), 6.91
(1H, d, J 8.7 Hz), 6.94e6.99 (3H, m), 7.05 (1H, d, J 7.5 Hz), 7.11 (1H,
dd, J 2.4, 8.7 Hz), 7.15e7.21 (3H, m), 7.28e7.37 (3H, m); dC (125 MHz,
CDCl3) 21.6 (CH3), 38.6 (CH2), 41.4 (CH), 46.0 (CH2), 117.2 (CH), 123.8
(CH), 127.3 (CH), 127.6 (CH), 127.8 (CH), 127.8 (CH), 128.2 (CH), 128.3
(CH), 128.5 (C), 128.7 (CH), 129.1 (CH), 131.1 (C), 136.4 (C), 138.3 (C),
138.6 (C), 140.2 (C), 169.1 (C); nmax (solid) 1671, 1488, 1416,
1371, 1323, 1272, 1229, 1027, 884, 810, 752, 731, 703, 691, 533, 490,
469 cmꢀ1; m/z (EI) 363 (12, Mþ), 361 (35, Mþ), 105 (100%);
HMRS (EI) Mþ, found 361.1231. C23H20ClNO requires 361.1228.
Further elution with DCM/5% Et2O gave a mixture of the 6-methyl
and 8-methyl-2-(4-chlorophenyl)-5-phenyl-1,2,4,5-tetrahydro-2-
benzazepin-3-ones 4p (0.16 g, 21%) as a foam in a ratio of 2.3:1;
dH (500 MHz, CDCl3) 1.99 (0.9H, s), 2.32 (2.1H, s), 3.16 (0.7H, dd, J
4.9, 13.6 Hz), 3.27 (0.3H, dd, J 9.6, 13.8 Hz), 3.37 (0.3H, dd, J 5.6,
13.8 Hz), 3.41 (0.7H, dd, J 11.1, 13.6 Hz), 4.61 (0.7H, d, J 16.3 Hz), 4.62
(0.7H, dd, J 4.9, 11.1 Hz), 4.77 (0.3H, d, J 16.4 Hz), 5.21 (0.3H, d, J
16.4 Hz), 5.33 (0.7H, d, J 16.3 Hz), 6.89e6.95 (1H, m), 7.00e7.08
(1.4H, m), 7.10e7.35 (9.6H, m); dC (125 MHz, CDCl3) 20.7 (CH3), 20.9
(CH3), 43.3 (CH2), 43.4 (CH), 44.1 (CH2), 45.5 (CH), 56.4 (CH2), 56.9
(CH2),126.7 (CH),126.8 (CH),127.0 (CH),127.1 (CH),127.2 (CH),127.7
(CH), 128.2 (CH), 128.8 (CH), 128.9 (CH), 129.2 (CH), 129.2 (CH),
129.4 (CH), 129.5 (CH), 131.8 (CH), 132.0 (C), 132.1 (C), 132.9 (CH),
134.7 (C), 135.5 (C), 136.4 (C), 137.1 (C), 137.8 (C), 139.4 (C), 141.6 (C),
141.8 (C), 144.4 (C), 146.4 (C), 171.3 (C), 171.6 (C); m/z (EI) 363 (7,
Mþ), 361 (21, Mþ), 270 (34), 207 (15), 206 (21), 193 (45), 192 (100),
178 (23%); HMRS (EI) Mþ, found 361.1228. C23H20ClNO requires
361.1228. Further elution with DCM/2% MeOH gave 6-chloro-4-
phenyl-3,4-dihydro-1H-quinolin-2-one 5e (0.08 g, 15%).
4.3.15. Reaction of-N-(2-methoxyphenyl)-3-phenylacrylamide (1n)
with TfOH. Following the general procedure for cyclisation, 1n
(0.5 g, 2.0 mmol) was heated under reflux with TfOH (2 mL) for 3 h
in CHCl3. TLC showed the presence of only one major product (Rf
0.5, Et2O). Purification by column chromatography on SiO2, eluting
with DCM gave 8-methoxy-4-phenyl-3,4-dihydro-1H-quinolin-2-
one 5n (0.42 g, 84%), identical to that previously obtained from 2n.
4.3.16. Reaction of N-4-methylbenzyl-N-(2-methoxyphenyl)-3-
phenylacrylamide (2o) with TfOH. Following the general pro-
cedure for cyclisation, 2o (0.72 g, 2.0 mmol) was heated under
reflux for 2 h in CHCl3. TLC showed the presence of three products
at Rf 0.8, 0.5 and 0.3 (Et2O). Purification by column chromatography
on SiO2, eluting with 1:1 petrol/DCM gave 1-(4-methylbenzyl)-6-
chloro-4-phenyl-3,4-dihydro-1H-quinolin-2-one 3o (0.28 g, 39%)
isolated as an oil; dH (500 MHz, CDCl3) 2.31 (3H, s), 3.06 (1H, dd, J
5.9, 15.7 Hz), 3.11 (1H, dd, J 8.0, 15.7 Hz), 4.25 (1H, dd, J 5.9, 8.0 Hz),
5.07 (1H, d, J 16.1 Hz), 5.25 (1H, d, J 16.1 Hz), 6.89e6.92 (2H,
m),7.03e7.16 (8H, m), 7.27e7.37 (2H, m); dC (125 MHz, CDCl3) 21.1
(CH3), 38.7 (CH2), 41.5 (CH), 45.8 (CH2), 117.2 (CH), 126.7 (CH), 127.6
(CH), 127.8 (CH), 127.8 (CH), 128.3 (CH), 128.5 (C), 129.1 (CH), 129.5
(CH), 131.1 (C), 133.4 (C), 137.0 (C), 138.2 (C), 140.2 (C), 169.1 (C); nmax
(film) 1676, 1595, 1488, 1414, 1368, 881, 796, 730, 699, 532,
491 cmꢀ1; m/z (EI) 363 (13, Mþ), 361 (38, Mþ), 105 (100%); HRMS
(CI) Mþ, found 361.1228. C23H20ClNO requires 361.1228. Further
elution with DCM/1% EtOAc gave 2-(4-chlorophenyl)-7-methyl-5-
phenyl-1,2,4,5-tetrahydro-2-benzazepin-3-one 4o (0.09 g, 13%) as
an oil; dH (500 MHz, CDCl3) 2.21 (3H, s), 3.16 (1H, dd, J 5.0, 13.7 Hz),
3.40 (1H, dd, J 11.0, 13.7 Hz), 4.58e4.63 (2H, m), 5.32 (1H, d, J
16.4 Hz), 6.83 (1H, s), 6.99 (1H, d, J 8.3 Hz), 7.03 (1H, d, J 7.7 Hz),
7.10e7.16 (4H, m), 7.21e7.25 (1H, m), 7.28e7.33 (4H, m); dC
(125 MHz, CDCl3) 21.1 (CH3), 43.4 (CH2), 45.8 (CH), 56.1 (CH2), 126.8
(CH), 127.1 (CH), 127.6 (CH), 128.3 (CH), 128.9 (CH), 129.2 (CH), 132.1
(C). 132.1 (C), 133.4 (CH), 138.5 (C), 139.9 (C), 141.8 (C), 146.3 (C),
171.5 (C); nmax (film) 1662, 1491, 1443, 1208, 1090, 907, 825, 726,
698 cmꢀ1; m/z (EI) 361 (7, Mþ), 207 (15), 206 (12), 193 (26), 192
(100), 178 (19%); HMRS (EI) Mþ, found 361.1221. C23H26ClNO re-
quires 361.1228. Further elution with DCM/10% EtOAc gave 6-
chloro-4-phenyl-3,4-dihydro-1H-quinolin-2-one 5e (0.24 g, 47%),
mp 183e184 ꢁC; dH (500 MHz, CDCl3) 2.89 (1H, dd, J 8.5, 16.3 Hz),
2.93 (1H, dd, J 6.9, 16.3 Hz), 4.26 (1H, t, J 7.7 Hz), 6.85 (1H, d, J
8.4 Hz), 6.88 (1H, d, J 2.0 Hz), 7.13e7.20 (3H, m), 7.27e7.31 (1H, m),
7.32e7.37 (2H, m), 9.54 (1H, br s); dC (125 MHz, CDCl3) 38.1 (CH2),
42.0 (CH), 117.1 (CH), 127.6 (CH), 127.8 (CH), 128.1 (CH), 128.4 (CH),
128.5 (C), 128.5 (C), 129.2 (CH), 135.8 (C), 140.7 (C), 171.1 (C); nmax
(solid) 1674, 1485, 1373, 831, 766, 700, 536, 491, 463 cmꢀ1; m/z (EI),
259 (33, Mþ); 258 (15), 257 (100, Mþ), 230 (15), 231 (17), 228 (43),
222 (27), 216 (13), 214 (39), 152 (16); (CI) 260 (33, MHþ), 259 (48,
Mþ), 258 (100, MHþ), 257 (97, Mþ), 222 (13), 180 (21), 105 (13%);
HMRS (CI) MHþ, found 258.0672. C15H13ClNO requires 258.0680.
4.3.18. Reaction of N-3,5-dimethylbenzyl-N-(2-methoxyphenyl)-3-
phenylacrylamide (2q) with TfOH. Following the general pro-
cedure for cyclisation, 2q (0.76 g, 2.0 mmol) was heated under
reflux for 2 h in CHCl3. TLC showed the presence of a major product
at Rf 0.8 (Et2O) plus minor products at Rf 0.5 and 0.3. Purification by
column chromatography on SiO2, eluting with 1:1 petrol/DCM gave
1-(3,5-dimethylbenzyl)-6-choro-4-phenyl-3,4-dihydro-1H-quino-
lin-2-one 3q (0.43 g, 57%) as a white solid; mp 153e154 ꢁC; dH
(500 MHz, CDCl3) 2.26 (6H, s), 3.09 (1H, dd, J 5.9, 15.8 Hz), 3.16 (1H,
dd, J 7.8, 15.8 Hz), 4.27 (1H, t, J 6.8 Hz), 4.94 (1H, d, J 16.1 Hz), 5.29
(1H, d, J 16.1 Hz), 6.77 (2H, s), 6.87 (1H, s), 6.92 (1H, d, J 8.7 Hz),
6.95e6.97 (1H, m), 7.12 (1H, dd, J 2.4, 8.7 Hz), 7.17 (2H, d, J 7.5 Hz),
7.27e7.37 (3H, m); dC (125 MHz, CDCl3) 21.4 (CH3), 38.6 (CH2), 41.4
(CH), 46.0 (CH2), 117.3 (CH), 124.4 (CH), 127.6 (CH), 127.8 (CH), 127.9
(CH), 128.3 (CH), 128.4 (C), 129.1 (CH), 131.0 (C), 136.4 (C), 138.3 (C),
138.4 (C), 140.3 (C), 169.1 (C); nmax (solid) 1677, 1658, 1595, 1488,
1420, 1366, 1194, 1158, 1016, 837, 817, 751, 698, 519 cmꢀ1; m/z (EI)
377 (31, Mþ), 375 (92, Mþ), 119 (100%); HMRS (EI) Mþ, found
375.1385. C24H22ClNO requires 375.1385. Further elution with
DCM/5% Et2O gave 2-(4-chlorophenyl)-6,8-dimethyl-5-phenyl-
1,2,4,5-tetrahydro-2-benzazepin-3-one 4q (0.16 g, 21%) as a white
solid; mp 209e210 ꢁC; dH (500 MHz, CDCl3) 1.94 (3H, s), 2.31 (3H, s),
3.23 (1H, dd, J 9.6, 13.8 Hz), 3.35 (1H, dd, J 5.5, 13.8 Hz), 4.63 (1H, dd,
J 5.5, 9.6 Hz), 4.74 (1H, d, J 16.4 Hz), 5.14 (1H, d, J 16.4 Hz), 6.83 (1H,
s), 6.96 (1H, s), 7.04 (2H, d, J 7.2 Hz), 7.12 (2H, dm, J 8.6 Hz), 7.18 (1H,
tm, J 7.2 Hz), 7.22e7.30 (4H, m); dC (125 MHz, CDCl3) 20.5 (CH3),
20.8 (CH3), 43.1 (CH), 44.0 (CH2), 56.9 (CH2), 126.7 (CH), 127.1 (CH),
127.6 (CH), 127.7 (CH), 128.8 (CH), 129.1 (CH), 131.9 (C), 132.5
(CH), 134.7 (C), 135.3 (C), 136.5 (C), 139.2 (C), 141.6 (C), 144.7 (C),
171.4 (C); nmax 1659, 1489, 1443, 1418, 1396, 1333, 1198, 1090, 996,
829, 776, 758, 708, 512, 500, 469, 433 cmꢀ1; m/z (EI) 377 (8, Mþ),
4.3.17. Reaction of N-3-methylbenzyl-N-(2-methoxyphenyl)-3-
phenylacrylamide (2p) with TfOH. Following the general pro-
cedure for cyclisation, 2p (0.72 g, 2.0 mmol) was heated under
reflux for 2 h in CHCl3. TLC showed the presence of a major product

F.D. King, S. Caddick / Tetrahedron 69 (2013) 8592e8601
8601
375 (23, Mþ), 207 (49), 206 (100%); HRMS (EI) Mþ, found
375.1384. C24H22ClNO requires 375.1384. Further elution with
DCM/2% MeOH gave 6-chloro-4-phenyl-3,4-dihydro-1H-quinolin-
2-one 5e (0.11 g, 21%).
4. Koltunov, K. Y.; Prakash, G. K. S.; Rasul, G.; Olah, G. A. Heterocycles 2004, 62,
757e772.
5. Elliott, M. C.; Wordingham, S. V. Synlett 2004, 898e900.
6. Park, J. O.; Youn, S. W. Org. Lett. 2010, 12, 2258e2261.
7. Weidner-Wells, M. A.; Fraga-Spano, S. A.; Turchi, I. J. J. Org. Chem. 1998, 63,
6319e6328.
8. Olah, G. A.; Liao, Q.; Casanova, J.; Bau, R.; Golam Rasul, G.; Prakash, G. K. S. J.
Chem. Soc., Perkin Trans. 2 1998, 2239e2242.
Acknowledgements
9. Medicinal Chemistry; Principles and Practice; King, F. D., Ed.; Royal Society of
Chemistry: 1994; p 301.
10. Lewis, F. D.; Elbert, J. E.; Upthagrove, A. L.; Hale, P. D. J. Org. Chem. 1991, 56,
553e561.
11. Olah, G. A.; Orlinkov, A.; Oxyzoglou, A. B.; Prakash, G. K. S. J. Org. Chem. 1995, 60,
7348e7350.
The authors would like to thank for the mass spectra Dr. Fred-
erick Campbell and Dr. Abil E. Aliev for assistance with NMR
studies.
12. Jennings, W. B.; Farrell, B. M.; Mallone, J. F. Acc. Chem. Res. 2001, 34,
885e894.
Supplementary data
13. Yamada, A.; Tomishima, M.; Hayashida, H.; Imanishi, M.; Spears, G. W.; Ito, K.;
Takahashi, F.; Miyake, H. EP1264820 A1, 2002.
14. Baruffini, A.; Borgna, P.; Pagani, G.; Gialdi, F. Farmaco Sci. 1967, 22, 895e916.
15. Narasimhan, B.; Belsare, D.; Pharande, D.; Mourya, V.; Dhake, A. Eur. J. Med.
Chem. 2004, 39, 827e834.
16. Ueda, S.; Okada, T.; Nagasawa, H. Chem. Commun. 2010, 2462e2464.
17. Goodman, K. B.; Neeb, M. J.; Sehon, C. A.; Viet, A. Q.; Wang, G. Z. US2008/21023
A1, 2008.
18. Bellamy, F. D.; Ou, K. Tetrahedron Lett. 1984, 25, 839e842.
19. Chen, Y.; Cushing, T. D.; Duquette, J. A.; Gonzalez, L.; De Turiso, F.; Hao, X.; He,
X.; Lucas, B.; McGee, L. R.; Reichelt, A.; Rzasa, R. M.; Seganish, J.; Shin, Y.; Zhang,
D. WO2008/118468 A1, 2008.
20. Evindar, G.; Batey, R. A. J. Org. Chem. 2006, 71, 1802e1808.
21. Houlihan, W. J.; Parrino, V. A.; Uike, Y. J. Org. Chem. 1981, 46, 4511e4515.
22. Wang, T.-C.; Chen, Y.-L.; Lee, K.-H.; Tzeng, C.-C. Synthesis 1997, 87e90.
23. Huang, Y.-B.; Yang, C.-T.; Yi, J.; Deng, X.-J.; Fu, Y.; Liu, L. J. Org. Chem. 2011, 76,
800e810.
Supplementary data contains characterising data for 1beg, 1jen
and NMR spectra for 2ber, 3deg, 3l, 3oeq, 4del, 4oeq, 5e and
5jen are available. Supplementary data related to this article can be
found at http://dx.doi.org/10.1016/j.tet.2013.07.075.
References and notes
1. King, F. D.; Caddick, S. Tetrahedron 2013, 69, 487e491.
2. Molino, B. F.; Liu, S.; Sambandam, A.; Guzzo, P. R.; Hu, M.; Zha, C.; Nacro, K.;
Manning, P. D.; Isherwood, M. L.; Fleming, K. N.; Cui, W.; Olson, R.E.
WO2007011820A2, 2007, CA 146, 184383, 2007; Croisier, P; Rodriquez, L.
USP4080449A, 1978, C.A. 88, 152456, 1978; Johnson, R. E.; Busacca, C. A. USP
5098901A, 1992, CA 117, 7949, 1992. Johnson, R. E.; Busacca, C. A. Tetrahedron
Lett. 1992, 33, 165; Wuensch, P.; Hasebein, P.; Schepmann, D. WO20100
12812A1, 2010, CA 152, 238800, 2010.
24. Yang, K.; Qiu, Y.; Jiang, S.; Wang, Z.; Li, Z. J. Org. Chem. 2011, 76, 3151e3159.
25. Amit, S.; Brindaban, R. J. Org. Chem. 2008, 73, 6867e6870.
3. Conley, R. T.; Knopta, W. N. J. Org. Chem. 1964, 29, 496e497.