Regioselective synthesis of 3-benzazepinones and unexpected 5-bromo-3-benzazepinones

Article abstract of DOI:10.1021/jo100378u

Figure presented A regioselective hydroamidation of 2-(1-alkynyl) phenylacetamides with Au(PPh₃)Cl/AgSbF₆ as the catalyst proceeded by a 7-endo-dig pathway to afford 3-benzazepinones. This method accommodates a broad range of alkyl and aryl alkynyl substitutes in moderate to high yields (63-91%). Moreover, unexpectedly, we also discovered a gold-mediated transformation from 2-(1-alkynyl)phenylacetamides to 5-bromo-3-benzazepinones, and AuBr₃ was found to not only play an activation role but also act as a reactant in the reaction for the first time.

Full text of DOI:10.1021/jo100378u

pubs.acs.org/joc
Regioselective Synthesis of 3-Benzazepinones and Unexpected
5-Bromo-3-benzazepinones
Lei Zhang,† Deju Ye,† Yu Zhou,† Guannan Liu,† Enguang Feng,† Hualiang Jiang,†,‡ and
Hong Liu*,†
†State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of
Sciences, 555 Zuchongzhi Road, Shanghai 201203, China, and School of Pharmacy, East China University
of Science and Technology, Shanghai 200237, China
‡
hliu@mail.shcnc.ac.cn
Received March 9, 2010
A regioselective hydroamidation of 2-(1-alkynyl)phenylacetamides with Au(PPh3)Cl/AgSbF6 as
the catalyst proceeded by a 7-endo-dig pathway to afford 3-benzazepinones. This method accom-
modates a broad range of alkyl and aryl alkynyl substitutes in moderate to high yields (63-91%).
Moreover, unexpectedly, we also discovered a gold-mediated transformation from 2-(1-alkynyl)-
phenylacetamides to 5-bromo-3-benzazepinones, and AuBr3 was found to not only play an activ-
ation role but also act as a reactant in the reaction for the first time.
Introduction
activation of alkynes; thus, they are efficient promoters to
prepare a large number of N-heterocycles.
Transition-metal-catalyzed reactions have matured into
indispensable techniques for organic synthesis. In recent
years, homogeneous silver and gold catalysis have emerged
as powerful tools for new organic transformations.1,2 In
particular, silver(I)3 and gold(III)4 salts have been proven
to be soft and carbophilic Lewis acids for electrophilic
The seven-membered nitrogen heterocyclic compounds
are important target molecules because of their frequent
occurrence in a number of bioactive natural products and
therapeutic agents. For example, benzazepinones are ubi-
quitous structural units found in a large array of natural
products5a,b and pharmaceuticals, and they possess a broad
spectrum of biological activities for the treatment of cardi-
ovascular diseases,5c tumor,5d pain,5e myocardial hyper-
trophy,5f and Alzheimer’s diseases.5g Therefore, the synthesis
of these structural motifs has been a subject of intensive
studies in recent years.
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DOI: 10.1021/jo100378u
r
Published on Web 05/05/2010
J. Org. Chem. 2010, 75, 3671–3677 3671
2010 American Chemical Society

Zhang et al.
JOCArticle
SCHEME 1. Cyclization of N-Methyl-2-(2-p-tolylethynylphenyl)-
acetamide 1a
With these issues in mind, we initiated our studies by
examining catalysts and reaction conditions using 1a as a
model substrate. The results are shown in Table 1. Indeed,
the reaction varied widely. However, the 7-endo-dig11 path-
way was observed to give the desired 3-benzazepinone (2a)
favorably. No reaction occurred in the presence of AgNO3,
Ag2CO3, and AgBF4 (entries 1-3, Table 1), and very low
conversion was detected with AgOTf (entry 4, Table 1). The
use of AgAsF6 led to product 2a in 31% (entry 5, Table 1).
However, AgSbF6 was found to be an effective catalyst for
the transformation and gave 2a in 62% yield at 100 °C for
24 h in anhydrous THF (entry 6, Table 1). After assessing
various solvents, polar solvents were found to have a detri-
mental effect on the reaction, and anhydrous toluene was
proved to be the optimum solvent (entries 7-11, Table 1).
The reaction temperature was found to be an important
factor on the process. For example, compound 2a was obtained
in only 15% yield when the temperature was reduced to 80 °C
(entry 12, Table 1). At an elevated temperature (from 80 to
120 °C), the reaction went to completion within 12 h and a
higher yield (74%) was observed, though a small portion of
decomposition of 1a occurred (entry 13, Table 1). When the
reaction was conducted without argon protection, decom-
position was observed and no desired product was obtained
(entry 14, Table 1). To accelerate the reaction, we then
assessed various cocatalysts. The addition of 10% Au(PPh3)-
Cl was found to noticeably promote the cyclization, afford-
ing 2a in 89% yield (entry 18, Table 1). Moreover, to our
surprise, an unexpected product 3a was detected when 15%
AuBr3 was used (entry 20, Table 1). An excess amount of
AuBr3 was needed to complete the full conversion of sub-
strate 1a (entry 23, Table 1). This may indicate that the role of
AuBr3 was that of a reactant more than catalytic activation,
which to our knowledge has never been reported before.12
THF was shown to be a better solvent than toluene for the
AuBr3 system. In order to decrease the amount of AuBr3, we
also tried to add an oxidant to make the reaction catalytic.
When the oxidant was PhI(OAc)2,13 the desired product 3a
was not detected (entry 25, Table 1). Selectfluor14 also gave
no satisfactory result. A dark brown stain was found at the
origin (spotting line) of the TLC plate, and the yield of
product 3a was as low as 25% (entry 26, Table 1). Disap-
pointingly, when the reaction was run in the presence of
CuBr2,10b 3a was not observed (entries 26 and 27, Table 1).
Br2-mediated reactions were also investigated, but product
3a was not obtained (entry 29, Table 1). Gratifyingly, a
catalytic amount of protic acid CH3COOH can accele-
rate the cyclization and improve the yield to 86% (entry 30,
Table 1).
Mitchell and co-workers recently reported a regioselective
synthesis of 3-benzazepinones by palladium-catalyzed intra-
molecular addition of amides to alkynes.6 However, only
2-(1-alkynyl)phenylacetamides with alkyl substitutions in
the alkynyl moiety could be obtained. In our ongoing efforts
to develop new convenient and efficient approaches to
synthesize highly valuable heterocyclic compounds with
transition-metal catalysts,7,8 we herein describe our recent
findings on intramolecular hydroamidation9 of 2-alkynyl
benzeneacetamides in the presence of silver and gold salts
for the synthesis of 3-benzazepinones as well as cyclization to
unexpected 5-bromo-3-benzazepinones.10
Results and Discussion
Our strategy access to benzazepinones (D) took advantage
of the readily prepared N-methyl-2-(2-substituted)acetamides
(1a) for a novel Ag(I)/Au(III)-catalyzed cyclization reaction
(Scheme 1). However, significant challenges were faced. Due
to the sensitive nature of 1a, it has three reactive nucleophilic
centers and two regioselective alkynyl carbons, which could
complicate the process. Therefore, there are six possible
pathways for its cyclization, leading to six products.
(6) Yu, Y.; Stephenson, G. A.; Mitchell, D. Tetrahedron Lett. 2006,
47, 3811.
(7) (a) Li, Z.; Sun, H.; Jiang, H.; Liu, H. Org. Lett. 2008, 10, 3263.
(b) Feng, E.; Huang, H.; Zhou, Y.; Ye, D.; Jiang, H.; Liu, H. J. Org. Chem.
2009, 74, 2846.
(8) (a) Ye, D.; Wang, J.; Zhang, X.; Zhou, Y.; Ding, X.; Feng, E.; Sun, H.;
Liu, G.; Jiang, H.; Liu, H. Green Chem. 2009, 11, 1201. (b) Liu, G.; Zhou, Y.;
Ye, D.; Zhang, D.; Ding, X. Adv. Synth. Catal. 2009, 351, 2605. (c) Zhou, Y.;
Feng, E.; Liu, G.; Ye, D.; Li, J.; Jiang, H.; Liu, H. J. Org. Chem. 2009, 74,
7344.
(9) For selected hydroamidation reactions, see: (a) Goossen, L. J.;
Rauhaus, J. E.; Deng, G. J. Angew. Chem., Int. Ed. 2005, 44, 4042. (b) Goossen,
L. J.; Blanchot, M.; Brinkmann, C.; Goossen, K.; Karch, R.; Rivas-Nass, A.
J. Org. Chem. 2006, 71, 9506. (c) Goossen, L. J.; Arndt, M.; Blanchot, M.;
Rudolphi, F.; Menges, F.; Niedner-Schatteburg, G. Adv. Synth. Catal. 2008,
350, 2701. (d) Goossen, L. J.; Salih, K. S. M.; Blanchot, M. Angew. Chem.,
Int. Ed. 2008, 47, 8492. (e) Goossen, L. J.; Blanchot, M.; Salih, K. S. M.;
Karch, R.; Rivas-Nass, A. Org. Lett. 2008, 10, 4497. (f) Yasui, Y.; Takemoto,
Y. Chem. Rec. 2008, 8, 386. (g) Goossen, L. J.; Ohlmann, D. M.; Lange, P. P.
Synthesis 2009, 160. (h) Goossen, L. J.; Blanchot, M.; Salih, K. S. M.;
Goosen, K. Synthesis 2009, 2283.
(11) (a) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734. (b)Baldwin,
J. E.; Thomas, R. C.; Kruse, L. I.; Silberman, L. J. Org. Chem. 1977, 42,
3846.
(12) For selected AuBr3-catalyzed reactions, see: (a) Asao, N.; Sato, K.;
Yamamoto, Y. Tetrahedron Lett. 2003, 44, 5675. (b) Asao, N.; Aikawa, H.;
Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 7458. (c) Praveen, C.; Kiruthiga,
P.; Perumal, P. T. Synlett 2009, 1990.
(13) (a) Kar, A.; Mangu, N.; Kaiser, H. M.; Bellerab, M.; Tse, M. K.
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Chem. Commun. 2008, 386. (b) Iglesias, A.; Muniz, K. Chem.—Eur. J. 2009,
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€
3672 J. Org. Chem. Vol. 75, No. 11, 2010

Zhang et al.
JOCArticle
TABLE 1. Optimization of the Reaction Conditionsa
yield (%)
entry
catalyst
cocatalyst
solvent
temp. (°C)
time (h)
2a
3a
1
2
3
4
5
6
7
8
9
10
11
12
13
14c
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
AgNO3
THF
THF
THF
THF
THF
THF
100
100
100
100
100
100
80
100
100
100
100
80
120
120
120
120
120
120
120
120
120
120
120
120
80
24
24
24
24
24
24
24
24
24
24
24
24
12
12
12
12
12
12
12
12
12
12
12
12
12
2
0b
Ag2CO3
AgBF4
AgOTf
AgAsF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
0b
0b
<10
31
62
<10
66
0b
CH2Cl2
PhMe
CH3CN
EtOH
DMF
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
THF
0b
0b
15
74
dec
0b
TEA
K2CO3
AcOH
Au(PPh3)Cl
AuBr3
0b
0b
89
53
<10
10b
23b
49b
61
15% AuBr3
35% AuBr3
100% AuBr3
120% AuBr3
120% AuBr3
81
35% AuBr3/200% PhI(OAc)2
35% AuBr3/150% Selectfluor
200% CuBr2
200% CuBr2
100% Br2/100% AgNO3/300% NaCO3
120% AuBr3
THF
CH3CN
THF
DMF
THF
THF
0b
25
80
80
80
25
12
12
12
5
0b
0b
0
86
CH3COOH
120
aReactions were carried out under Ar with 10 mol % of the catalyst and 10 mol % of the cocatalyst unless otherwise noted. b1a was recovered. cThe
reaction was carried out under air.
The structures of 2a and 3a were confirmed by 1H NMR,
13C NMR, mass spectrometry, and X-ray crystallography
(see the Supporting Information).15
We then investigated the substrate scope of the two
transformations. The results are shown in Tables 2 and 3.
The chain length and electronic and steric effects which
would influence the reactivity and the regiochemical out-
comes of the studied reactions were examined.
In the case of Au(PPh3)Cl/AgSbF6-catalyzed cyclization,
substrates 1 bearing various alkyl and aryl alkynyl substi-
tutes could react to give the desired products 2 in moderate
to high yields (Table 2). When R1 was a para- or meta-
substituted aryl group, the corresponding products were
obtained in good yields (entries 3 and 4, Table 2). However,
for the ortho substitution, a moderate yield was obtained,
presumably due to steric effects (entry 5, Table 2). When R1
was a 4-halogen-substituted phenyl group, 1f and 1g reacted
satisfactorily to give 2f and 2g in 90% and 72% yields,
respectively (entries 6 and 7, Table 2). Cyclization of 1h,
which bears an electron-donating R1 (p-OMe), gave 2h in
good yield (entry 8, Table 2), whereas 1i bearing an electron-
withdrawing R1 (p-CF3) resulted in a poor yield (entry 9,
Table 2). The cyclization was also successfully extended to
benzyl amide 1k in 70% yield (entry 11, Table 2). Only a trace
amount of 2j was obtained when R1 was a heteroaromatic
group, and decomposition of 1j was observed (entry 10,
Table 2). The reaction of aromatic amide 1l gave only a trace
amount of yield presumably due to the decreased nucleophi-
licity of the amide NH (entry 12, Table 2).
Similarly, the synthesis of 5-bromo-3-benzazepinones via
AuBr3-mediated cyclization also tolerated various R1 and R2
substitutes in moderate to good yields (Table 3). However, 1j
with heteroaromatic substituted R1, 1l bearing an aromatic
amide, and 1m with bulky tert-butyl R2 turned out to be poor
substrates, resulting in trace yields (entries 9, 11, and 12,
Table 3).
A plausible mechanism accounting for the formation of
3-benzazepinones via Au(PPh3)Cl/AgSbF6-catalyzed cycli-
zation is depicted in Scheme 2. As has been postulated for
other Au-catalyzed nucleophilic additions, the catalyst here
is the gold complex typically precipitated from AgSbF6 and
Au(PPh3)Cl in a 1:1 ratio.16 The reaction is initiated with
alkyne activation by the gold complex, followed by intra-
molecular nucleophilic attack of the amide nitrogen at the
(15) CCDC 745837 and CCDC 745838 contain the supplementary crys-
tallographic data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.
uk/data_request/cif.
J. Org. Chem. Vol. 75, No. 11, 2010 3673

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TABLE 2. Synthesis of 3-Benzazepinones via Au(PPh3)Cl/AgSbF6-
TABLE 3. Synthesis of 5-Bromo-3-benzazepinones via AuBr3-
Catalyzed Cyclizationa
Mediated Cyclizationa
aThe reaction was carried out in the presence of AuBr3 (120 mol %)
and CH3COOH (10 mol %) in anhydrous THF with Ar protection at
120 °C.
SCHEME 2. Proposed Mechanism for Au(PPh3)Cl/AgSbF6-
Catalyzed Hydroamidation of 1a to 2a
aThe reactions were carried out in the presence of AgSbF6 (10 mol %)
and Au(PPh3)Cl (10 mol %) in anhydrous toluene under Ar protection
at 120 °C unless otherwise noted. bThe reaction time was prolonged to 24 h.
triple bond in an endo-dig fashion to give the seven-mem-
bered intermediate 4. Then elimination of a proton affords
the product 2a with regeneration of the catalyst. The low
yield of 2i may due to the electron-withdrawing effect of CF3,
which made alkyne activation difficult for the catalyst
(entry 9, Table 2). On the contrary, electron-donating sub-
stitutes (CH3, OMe) are favorable for the gold complex to
activate the alkynyl moieties (entries 3-5 and 8, Table 2).
The different outcomes observed in reactions mediated
by AuBr3 suggest that a different mechanism is involved
(Scheme 3). We reason that in the presence of AuBr3,
reactant 1a would undergo nucleophilic cyclization and then
reductive elimination, leading to the product 3a.17 Initially,
~
~
(16) (a) Nieto-Oberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.;
ꢀ
Cardenas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402.
(b) Toullec, P. Y.; Genin, E.; Leseurre, L.; Genet, J. P.; Michelet, V. Angew.
Chem., Int. Ed. 2006, 45, 7427. (c) Asao, N.; Aikawa, H.; Tago, S.; Umetsu,
K. Org. Lett. 2007, 9, 4299.
(17) Kharasch, M. S.; Isbell, H. M. J. Am. Chem. Soc. 1931, 53, 3053.
3674 J. Org. Chem. Vol. 75, No. 11, 2010

Zhang et al.
JOCArticle
SCHEME 3. Proposed Mechanism for the AuBr3-Mediated Cyclization of 1a to 3a
reactant 1a is activated by AuBr3. Regioselective nucleophi-
lic attack of the amide nitrogen to the gold-coordinated triple
bond in a 7-endo-dig fashion provides intermediate 5, which
upon subsequent reductive elimination10b produces the seven-
membered 5-bromo-3-benzazepinone 3a. This mechanistic
picture differs from the generally accepted homogeneous gold-
catalyzed reactions in that AuBr3 not only plays an activa-
tion role but also acts as a reactant in the reaction.12
28.6 22.5 19.9 19.4 14.0 13.7; MS (EI, m/z) 299 [M]þ; HRMS (EI)
calcd for C20H29NO [M]þ 299.2249, found 299.2252.
N-Butyl-2-[2-(p-tolylethynyl)phenyl]acetamide (1c): 1H NMR
(CDCl3, 300 MHz) δ 7.56 (d, J=6.6 Hz, 1H), 7.42 (d, J=8.1 Hz,
2H), 7.37-7.26 (m, 3H), 7.17 (d, J=7.8 Hz, 2H), 5.63 (br s, 1H),
3.81 (s, 2H), 3.19 (q, J=6.6 Hz, 2H), 2.37 (s, 3H), 1.40-1.30 (m,
2H), 1.26-1.14 (m, 2H), 0.77 (t, J = 7.5 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 170.3 138.9 137.0 132.3 131.4 130.1 129.2
128.8 127.4 123.4 119.5 94.5 86.7 42.9 39.4 31.5 21.5 19.9 13.6;
MS (EI, m/z) 305 [M]þ; HRMS (EI) calcd for C21H23NO [M]þ
305.1780, found 305.1780.
Conclusion
N-Butyl-2-[2-(m-tolylethynyl)phenyl]acetamide (1d): 1H NMR
(CDCl3, 300 MHz) δ 7.57 (d, J=6.9 Hz, 1H), 7.35-7.22 (m, 6H),
7.17 (d, J=7.5 Hz, 1H), 5.61 (br s, 1H), 3.82 (s, 2H), 3.19 (q, J=
6.6 Hz, 2H), 2.36 (s, 3H), 1.39-1.31 (m, 2H), 1.26-1.15 (m, 2H),
0.78(t, J=7.5 Hz, 3H); 13C NMR (75MHz, CDCl3) δ 170.3 138.1
137.1 132.4 132.0 130.1 129.5 128.9 128.6 128.3 127.4 123.3 122.4
94.4 87.0 42.9 39.4 31.5 21.2 19.9 13.6; MS (EI, m/z) 305 [M]þ;
HRMS (EI) calcd for C21H23NO [M]þ 305.1780, found 305.1776.
N-Butyl-2-[2-(4-fluorophenylethynyl)phenyl]acetamide (1f): 1H
NMR (CDCl3, 300 MHz) δ 7.57-7.49 (m, 3H), 7.35-7.27 (m,
3H), 7.05 (t, J=8.4 Hz, 2H), 5.52 (br s, 1H), 3.81 (s, 2H), 3.19 (q,
J=6.3 Hz, 2H), 1.38-1.31 (m, 2H), 1.26-1.17 (m, 2H), 0.78 (t,
In summary, we have developed a simple strategy for
the synthesis of 3-benzazepinones by Au(PPh3)Cl/AgSbF6-
catalyzed intramolecular hydroamidation with high regios-
electivity and moderate to good yields. Importantly and
unexpectedly, we also have uncovered the gold-mediated
transformation to more synthetically versatile 5-bromo-3-
benzazepinones, in which AuBr3 not only plays an activation
role but also acts as a reactant. As a result of a diverse
assortment of biological activities of benzodiazepines, it is
believed that these new approaches open the door to prepare
new members of this valuable family.
J=7.2, 3H);13C NMR(75MHz, CDCl3) δ 170.2 162.7 (d, JC-F
=
186.7 Hz) 137.0 133.5 133.4 132.3 130.2 129.0 127.5 123.2 118.8
115.9 115.7 93.3 86.9 42.9 39.4 31.5 19.9 13.6; MS (EI, m/z) 309
[M]þ; HRMS (EI) calcd for C20H20FNO [M]þ 309.1529, found
309.1525.
Experimental Section
Typical Procedure for the Synthesis of N-Methyl-2-[2-(p-
tolylethynyl)phenyl]acetamide (1a). (i) To a solution of 1-ethyl-
3-(3-dimethylaminopropyl)carbodiimide (EDCI) (1.2 mmol)
and 2-iodophenylacetic acid (1.0 mmol) in CH2Cl2 (10 mL)
was added a catalytic amount of 4-dimethylaminopyridine
(DMAP), followed by addition of methylamine hydrochloride
(1.0 mmol) 1 h later. The resulting mixture was stirred at room
temperature. When the starting materials were completely con-
sumed as monitored by TLC, the reaction mixture was diluted
with CH2Cl2, washed with water, dried with anhydrous Na2SO4,
and concentrated. The residue was purified by column chroma-
tography to provide 2-(2-iodophenyl)-N-methylacetamide. (ii)
To a solution of 2-(2-iodophenyl)-N-methylacetamide (1.0 mmol)
and 1-ethynyl-4-methylbenzene (1.2 mmol) in Et3N (5 mL) were
added Pd(PPh3)2Cl2 (0.02 mmol) and CuI (0.01 mmol). The re-
sulting mixture was stirred under argon at room temperature
and was monitored by TLC to establish completion. When the
reaction was complete, the solvent was removed under reduced
pressure. The residue was purified by column chromatography
to afford 1a as a white solid: 1H NMR (CDCl3, 300 MHz) δ 7.56
(d, J=6.0 Hz, 1H), 7.43 (d, J=8.1 Hz, 2H), 7.36-7.28 (m, 3H),
7.17 (d, J=7.8 Hz, 2H), 5.56 (br s, 1H), 3.83 (s, 2H), 2.75 (d, J=
4.5 Hz, 3H), 2.38 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 170.1
138.8 136.8 132.3 131.4 130.1 129.2 128.8 127.4 123.5 119.5 94.5
86.5 42.6 26.5 21.5; MS (EI, m/z) 263 [M]þ; HRMS (EI) calcd for
C18H17NO [M]þ 263.1310, found 263.1303.
N-Butyl-2-[2-(4-chlorophenylethynyl)phenyl]acetamide (1g): 1H
NMR (CDCl3, 300 MHz) δ 7.56 (d, J=6.9 Hz, 1H), 7.46 (d, J=
7.5 Hz, 2H), 7.34-7.27 (m, 5H), 5.49 (br s, 1H), 3.80 (s, 2H), 3.19
(q, J=6.0Hz, 2H), 1.40-1.30 (m, 2H), 1.26-1.14 (m, 2H), 0.78 (t,
J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 170.2 137.1 134.7
132.8 132.4 130.2 129.2 128.8 127.5 123.1 121.2 93.2 88.1 42.9 39.4
31.5 19.9 13.6; MS (EI, m/z) 325 [M]þ; HRMS (EI) calcd for
C20H20ClNO [M]þ 325.1233, found 325.1227.
N-Butyl-2-[2-(4-methoxyphenylethynyl)phenyl]acetamide (1h):
1H NMR (CDCl3, 300 MHz) δ 7.55-7.52 (m, 1H), 7.47 (d, J=
9.0Hz, 2H), 7.34-7.26(m,3H), 7.88 (d, J=9.0Hz, 2H), 5.68 (brs,
1H), 3.81 (s, 3H), 3.80 (s, 2H),3.18 (q, J=6.6 Hz, 2H), 1.37-1.30
(m, 2H), 1.24-1.16 (m, 2H), 0.78 (t, J=7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 170.4 159.9 136.8 133.0 132.1 130.1 128.6
127.4 123.6 114.7 114.1 94.4 86.1 55.3 42.9 39.3 31.4 19.8 13.6;
MS (EI, m/z) 321 [M]þ; HRMS (EI) calcd for C21H23NO2 [M]þ
321.1729, found 321.1732.
N-Benzyl-2-[2-(p-tolylethynyl)phenyl]acetamide (1k): 1H NMR
(CDCl3, 300 MHz) δ 7.55 (dd, J=6.9, 1.5 Hz, 1H), 7.39-7.28 (m,
5H), 7.19-7.12 (m, 7H), 5.90 (br s, 1H), 4.41 (d, J=6.0 Hz, 2H),
3.89 (s, 2H), 2.37 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 170.4
138.9 138.0 136.6 132.4 131.9 131.4 130.9 130.2 129.2 128.9 128.5
127.5 127.4 127.2 123.5 119.4 94.7 86.7 43.6 42.8 21.5; MS (EI,
m/z) 339 [M]þ; HRMS (EI) calcd for C24H21NO [M]þ 339.1623,
found 339.1617.
N-Butyl-2-(2-oct-1-ynyl-phenyl)acetamide (1b):1HNMR(CDCl3,
300 MHz) δ 7.43 (dd, J=6.6, 2.1 Hz, 1H), 7.31-7.18 (m, 3H), 5.60
(br s, 1H), 3.73 (s, 2H), 3.18 (q, J=6.6 Hz, 2H), 2.43 (t, J=7.2 Hz,
2H), 1.66-1.56 (m, 2H), 1.49-1.19 (m, 10H), 0.90 (t, J=6.6 Hz,
3H), 0.87 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 170.6
136.8 132.4 129.8 128.2 127.2 123.9 95.4 78.7 42.6 39.3 31.5 31.3 28.7
2-(2-Oct-1-ynylphenyl)-N-p-tolylacetamide (1l): 1H NMR
(CDCl3, 400 MHz) δ 7.47-7.23 (m, 6H), 7.06 (d, J=8.4 Hz,
2H), 3.87 (s, 2H), 2.46 (t, J=6.8 Hz, 2H), 2,28 (s, 3H), 1.64-
1.56 (m, 2H), 1.46-1.39 (m, 2H), 1.28-1.25 (m, 4H), 0.87 (t,
J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 168.6 136.5
J. Org. Chem. Vol. 75, No. 11, 2010 3675

Zhang et al.
JOCArticle
135.3 133.8 132.6 129.9 129.5 129.3 128.4 127.5 123.8 119.8
96.0 78.9 43.9 31.3 28.7 28.6 22.5 20.8 19.5 14.0; MS (EI, m/z)
333 [M]þ; HRMS (EI) calcd for C23H27NO [M]þ 333.2093,
found 333.2094.
132.0 130.4 130.3 128.6 128.5 127.7 122.1 93.1 91.1 42.8 39.4 31.5
29.6 19.8 13.6; MS (EI, m/z) 292 [M]þ; HRMS (EI) calcd for
C19H20N2O [M]þ 292.1576, found 292.1573.
Typical Procedure for the Synthesis of 3-Methyl-4-p-tolyl-1,3-
dihydro-3-benzazepin-2-one (2a). A mixture of 1a (0.1 mmol) and
Au(PPh3)Cl (0.01 mmol)/AgSbF6 (0.01 mmol) in 4 mL of
anhydrous toluene was heated at 120 °C in a sealed tube under
argon protection for 12 h. After the reaction was cooled to
ambient temperature, the solvent was removed under reduced
pressure, and the residue was purified by a flash column chro-
N-tert-Butyl-2-(2-oct-1-ynylphenyl)acetamide (1m): 1H NMR
(CDCl3, 300 MHz) δ 7.42 (d, J=6.9 Hz, 1H), 7.30-7.17 (m, 3H),
5.53 (br s, 1H), 3.63 (s, 2H), 2.44 (t, J=6.9 Hz, 2H), 1.70-1.57
(m, 2H), 1.50-1.41 (m, 2H), 1.33-1.27 (m, 4H), 1.29 (s, 9H),
0.91 (t, J=6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.8
137.3 132.4 129.7 128.2 127.0 123.7 95.2 78.9 51.0 43.9 31.3 28.7
28.6 28.5 22.5 19.5 14.5; MS (EI, m/z) 299 [M]þ; HRMS (EI)
calcd for C20H29NO [M]þ 299.2249, found 299.2251.
1
matography to yield 2a as a white solid: H NMR (300 MHz,
CDCl3) δ 7.40-7.34 (m, 6H), 7.25-7.23 (m, 2H), 6.78 (s, 1H),
3.70 (br s, 1H), 3.57(br s, 1H), 2.86 (s, 3H), 2.40 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 169.7 143.3 138.7 134.9 133.8 133.5
129.5 128.7 128.3 127.3 127.2 126.9 119.6 42.9 35.1 21.2; MS (EI,
m/z) 263 [M]þ; HRMS (EI) calcd for C18H17NO [M]þ 263.1310,
found 263.1308.
Typical Procedure for the Synthesis of N-Butyl-2-[2-(o-
tolylethynyl)phenyl]acetamide (1e). (i) To a solution of EDCI
(1.2 mmol) and 2-iodophenylacetic acid (1.0 mmol) in CH2Cl2
(10 mL) was added a catalytic amount of DMAP, followed by
addition of n-butylamine (1.0 mmol) 1 h later. The resulting
mixture was stirred at room temperature. When the starting
materials were completely consumed monitored with TLC, the
reaction mixture was diluted with CH2Cl2, washed with water,
dried with anhydrous Na2SO4, and concentrated. The residue
was purified by column chromatography to provide N-butyl-
2-(2-iodophenyl)acetamide. (ii) To a solution of N-butyl-2-(2-
iodophenyl)acetamide (1.0 mmol) and TMS-acetylene (1.2 mmol)
in Et3N (5 mL) were added Pd(PPh3)2Cl2 (0.02 mmol) and CuI
(0.01 mmol). The resulting mixture was stirred under argon at
room temperature and was monitored by TLC to establish
completion. When the reaction was complete, the solvent was re-
moved under reduced pressure. The residue was directly purified
by column chromatography to afford N-butyl-2-(2-((trimethyl-
silyl)ethynyl)phenyl)acetamide. (iii) To a solution of N-butyl-
2-(2-((trimethylsilyl)ethynyl)phenyl)acetamide in THF was added
ca. 1.5-2.0 equiv of TBAF (1 M THF solution), and the mixture
was stirred for about 30 min (completion monitored by TLC).
Upon completion, the reaction was treated with water, extracted
with CH2Cl2, washed with H2O, dried (Na2SO4), and concen-
trated in vacuo. Purification by flash column chromatography
gave N-butyl-2-(2-ethynylphenyl)acetamide. (iv) To a solution
of N-butyl-2-(2-ethynylphenyl)acetamide (1.0 mmol) and 1-iodo-
2-methylbenzene (1.2 mmol) in Et3N (5 mL) were added Pd-
(PPh3)2Cl2 (0.02 mmol) and CuI (0.01 mmol). The resulting
mixture was stirred under argon at room temperature and was
monitored by TLC to establish completion. When the reaction
was complete, the solvent was removed under reduced pressure.
The residue was purified by column chromatography to afford
1e as a white solid: 1H NMR (CDCl3, 400 MHz) δ 7.59 (dd, J=
6.8, 2.0 Hz, 1H), 7.50 (d, J=7.2 Hz, 1H),7.37-7.23 (m, 5H),
7.20-7.16 (m, 1H), 5.53 (br s, 1H), 3.84 (s, 2H), 3.18 (q, J=6.8
Hz, 2H), 2.51 (s, 3H), 1.38-1.31 (m, 2H), 1.24-1.15 (m, 2H),
0.77 (t, J=7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 170.2
139.9 136.8 132.5 132.0 130.1 129.6 128.9 128.7 127.4 125.7 123.5
122.4 93.2 91.1 42.8 39.4 31.4 20.8 19.9 13.6; MS (EI, m/z) 305
[M]þ; HRMS (EI) calcd for C21H23NO [M]þ 305.1780, found
305.1789.
1
3-Butyl-4-hexyl-1,3-dihydro-3-benzazepin-2-one (2b): H NMR
(400 MHz, CDCl3) δ 7.29-7.23 (m, 3H), 7.20 (d, J=6.4 Hz, 1H),
6.52 (s, 1H), 4.13 (br s, 1H), 3.61 (br s, 1H), 3.33 (br s, 1H), 3.07
(br s, 1H), 2.60 (br s, 1H), 2.31 (br s, 1H), 1.53-1.25 (m, 10H),
1.07-1.04 (m, 2H), 0.89 (t, J=6.8 Hz, 3H) 0.76 (t, J=7.6 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 169.1 141.3 133.6 133.4 128.2 127.9
126.8 126.7 119.9 43.1 42.7 34.9 31.5 30.2 28.8 28.4 22.5 19.6 13.9
13.6; MS (EI, m/z) 299 [M]þ; HRMS (EI) calcd for C20H29NO
[M]þ 299.2249, found 299.2253.
3-Butyl-4-p-tolyl-1,3-dihydro-3-benzazepin-2-one (2c): 1H NMR
(300 MHz, CDCl3) δ 7.41-7.32 (m, 6H), 7.23 (d, J=8.1 Hz, 2H),
6.84 (s, 1H), 4.08 (br s, 1H), 3.69 (br s, 1H), 3.51 (br s, 1H), 2.83 (br
s, 1H), 2.40 (s, 3H), 1.18-1.08 (m, 2H), 0.94-0.82 (m, 2H), 0.61 (t,
J=7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.5 142.3 138.6
134.9 133.9 133.8 129.4 128.6 128.5 128.2 127.3 127.2 126.9 121.6
45.1 43.1 29.8 21.2 19.3 13.5; MS (EI, m/z) 305 [M]þ; HRMS (EI)
calcd for C21H23NO [M]þ 305.1780, found 305.1781.
3-Butyl-4-m-tolyl-1,3-dihydro-3-benzazepin-2-one (2d): 1H NMR
(300 MHz, CDCl3) δ 7.36-7.31 (m, 7H), 7.21-7.17 (m, 1H), 6.86
(s, 1H), 4.09 (br s, 1H), 3.72 (br s, 1H), 3.52 (br s, 1H), 2.83 (br s,
1H), 2.42 (s, 3H), 1.18-1.08 (m, 2H), 0.94-0.82 (m, 2H), 0.62 (t,
J=6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.6 142.4 138.4
137.8 133.9 133.8 129.3 128.7 128.6 128.3 127.9 127.2 126.9 124.5
121.9 45.1 43.1 29.8 21.4 19.3 13.5; MS (EI, m/z) 305 [M]þ; HRMS
(EI) calcd for C21H23NO [M]þ 305.1780, found 305.1784.
3-Butyl-4-o-tolyl-1,3-dihydro-3-benzazepin-2-one (2e): 1H NMR
(400 MHz, CDCl3) δ 7.47 (d, J=6.8 Hz, 1H), 7.37-7.26 (m, 6H),
7.23 (d, J=7.2 Hz, 1H), 6.65 (s, 1H), 3.93 (br s, 1H), 3.76 (br s, 1H),
3.64 (br s, 1H), 2.61 (br s, 1H), 2.33 (s, 3H), 1.76-1.68 (m, 2H),
0.94-0.86 (m, 2H), 0.63 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 168.7 141.9 137.9 136.0 133.7 133.2 130.5 129.9 128.7
128.3 127.3 126.9 126.3 122.4 44.6 43.6 30.0 19.8 19.5 13.5; MS (EI,
m/z) 305 [M]þ; HRMS (EI) calcd for C21H23NO [M]þ 305.1780,
found 305.1782.
3-Butyl-4-(4-fluorophenyl)-1,3-dihydro-3-benzazepin-2-one (2f):
1H NMR (300 MHz, CDCl3) δ 7.49 (dd, J=8.4, 5.4 Hz, 2H),
7.35 (s, 4H),7.31 (t, J=8.4 Hz, 2H), 6.82 (s, 1H), 4.08 (br s, 1H),
3.72 (br s, 1H), 3.51 (br s, 1H), 2.77 (br s, 1H), 1.18-1.08 (m,
2H), 0.95-0.82 (m, 2H), 0.62 (t, J = 6.9 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 169.4 162.8 (d, JC-F=185.2 Hz) 141.2 133.8
133.5 129.2 129.1 128.9 128.3 127.2 127.0 122.1 115.9 115.7 45.0
43.1 29.7 19.3 13.5; MS (EI, m/z) 309 [M]þ; HRMS (EI) calcd for
C20H20FNO [M]þ 309.1529, found 309.1495.
N-Butyl-2-[2-(4-trifluoromethylphenylethynyl)phenyl]acetamide
(1i): 1H NMR (CDCl3, 300 MHz) δ 7.66-7.58 (m, 5H),
7.41-7.30 (m, 3H), 5.41 (br s, 1H), 3.83 (s, 2H), 3.20 (q, J=
6.9 Hz, 2H), 1.40-1.31 (m, 2H), 1.27-1.14 (m, 2H), 0.77 (t, J=
7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 170.1 137.2 132.5
131.7 130.3 130.2 129.9 129.5 127.5 126.5 125.3 125.2 125.1 122.7
92.8 89.4 42.8 39.3 31.4 19.8 14.0; MS (EI, m/z) 359 [M]þ;
HRMS (EI) calcd for C21H20F3NO [M]þ 359.1497, found
359.1503.
3-Butyl-4-(4-chlorophenyl)-1,3-dihydro-3-benzazepin-2-one (2g):
1H NMR (300 MHz, CDCl3) δ 7.43 (dd, J=14.4, 8.1 Hz, 4H),
7.35 (m, 4H), 6.85 (s, 1H), 4.08 (br s, 1H), 3.73 (br s, 1H), 3.49 (br
s, 1H), 2.76 (br s, 1H), 1.17-1.07 (m, 2H), 0.92-0.84 (m, 2H),
0.62 (t, J=6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.5
141.1 136.3 134.5 133.8 133.4 129.0 128.7 128.4 127.3 127.1 122.5
45.1 43.0 29.7 19.3 13.5; MS (EI, m/z) 325 [M]þ; HRMS (EI)
calcd for C20H20ClNO [M]þ 325.1233, found 325.1225.
N-Butyl-2-(2-pyridin-4-ylethynylphenyl)acetamide (1j): 1H NMR
(CDCl3, 400 MHz) δ 8.66 (br s, 2H), 7.60 (d, J=7.2 Hz, 1H),
7.42-7.32 (m, 5H), 5.41 (br s, 1H), 3.82 (s, 2H), 3.20 (q, J=6.8 Hz,
2H), 1.40-1.33 (m, 2H), 1.26-1.17 (m, 2H), 0.79 (t, J=7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 170.1 148.4 137.6 132.9 132.6
3676 J. Org. Chem. Vol. 75, No. 11, 2010

Zhang et al.
JOCArticle
3-Butyl-4-(4-methoxyphenyl)-1,3-dihydro-3-benzazepin-2-one
(2h): 1H NMR (300 MHz, CDCl3) δ 7.45 (d, J=9.0 Hz, 2H), 7.33
(m, 4H), 6.85 (d, J=9.0 Hz, 2H), 6.80 (s, 1H), 4.08 (br s, 1H),
3.86 (s, 3H), 3.71 (br s, 1H), 3.51 (br s, 1H), 2.85 (br s, 1H),
1.17-1.07 (m, 2H), 0.93-0.81 (m, 2H), 0.62 (t, J=6.9 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 169.5 159.8 141.9 133.8 130.2
128.6 128.5 128.2 127.1 126.9 121.1 114.1 55.3 45.1 43.1 29.7 19.3
13.5; MS (EI, m/z) 321 [M]þ; HRMS (EI) calcd for C21H23NO2
[M]þ 321.1729, found 321.1725.
127.2 125.6 116.4 45.1 43.3 29.6 19.8 19.4 13.5; MS (EI, m/z) 383
[M]þ; HRMS (EI) calcd for C21H22BrNO [M]þ 383.0885, found
383.0878.
5-Bromo-3-butyl-4-(4-fluorophenyl)-1,3-dihydro-3-benzazepin-
2-one (3f): 1H NMR (300 MHz, CDCl3) δ 7.76-7.73 (m, 1H),
7.51-7.46 (m, 2H), 7.42-7.38 (m, 2H), 7.35-7.30 (m, 1H), 7.15
(t, J=8.7 Hz, 2H), 3.96-3.86 (m, 1H), 3.71 (s, 2H), 2.57-2.48
(m, 1H), 1.22-0.99 (m, 2H), 1.92-1.76 (m, 2H), 0.63 (t, J=7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 169.6 162.7 (d, JC-F
=
3-Benzyl-4-p-tolyl-1,3-dihydro-3-benzazepin-2-one (2k): 1H NMR
(300 MHz, CDCl3) δ 7.38-7.34 (m, 2H), 7.33-7.19 (m, 6H), 7.07-
6.94 (m, 3H), 6.75 (s, 1H), 6.54 (d, J=7.5 Hz, 2H), 5.39 (br s, 1H),
186.2 Hz) 138.9 135.7 135.1 131.9 131.8 130.4 129.9 127.5 127.3
116.7 115.5 115.3 44.9 42.7 29.7 19.3 13.5; MS (EI, m/z) 387
[M]þ; HRMS (EI) calcd for C20H19BrFNO [M]þ 387.0634,
found 387.0636.
3.93 (br s, 1H), 3.79 (br s, 1H), 3.62 (br s, 1H), 2.34 (s, 3H); 13
C
NMR (75 MHz, CDCl3) δ 169.7 142.1 138.7 136.9 134.7 133.9 133.4
129.4 128.8 128.3 127.9 127.4 127.2 127.1 127.0 126.7 122.2 48.6 42.9
21.2; MS (EI, m/z) 339[M]þ;HRMS(EI) calcdforC24H21NO[M]þ
339.1623, found 339.1630.
5-Bromo-3-butyl-4-(4-chlorophenyl)-1,3-dihydro-3-benzazepin-
2-one (3g): 1H NMR (300 MHz, CDCl3) δ 7.76-7.69 (m, 1H),
7.44-7.30 (m, 7H), 3.97-3.87 (m, 1H), 3.70 (s, 2H), 2.56-2.46
(m, 1H), 1.15-1.00 (m, 2H), 0.89-0.79 (m, 2H), 0.63 (t, J =
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.6 138.8 135.6
135.0 134.9 131.3 130.5 129.9 128.6 127.5 127.4 116.8 44.9 42.7
29.7 19.3 13.5; MS (EI, m/z) 403 [M]þ; HRMS (EI) calcd for
C20H19BrClNO [M]þ 403.0339, found 403.0342.
5-Bromo-3-butyl-4-(4-methoxyphenyl)-1,3-dihydro-3-benzazepin-
2-one (3h): 1H NMR (400 MHz, CDCl3) δ 7.75-7.72 (m, 1H),
7.42 (d, J=8.8 Hz, 2H), 7.39-7.37 (m, 2H), 7.32-7.30 (m, 1H),
6.96 (d, J=8.8 Hz, 2H), 3.95-3.89 (m, 1H), 3.87 (s, 3H), 3.73
(dd, J=14.0, 12.0 Hz, 2H), 3.46- 3.42 (m, 2H), 2.59-2.52 (m,
1H), 1.20- 1.01 (m, 2H), 0.89-0.79 (m, 2H), 0.63 (t, J=7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 169.7 159.8 139.7 135.9
135.2 131.3 130.1 129.8 129.3 127.3 127.2 115.9 113.5 55.3 44.9
42.7 29.7 19.3 13.5; MS (EI, m/z) 399 [M]þ; HRMS (EI) calcd for
C21H22BrNO2 [M]þ 399.0834, found 399.0827.
3-Benzyl-5-bromo-4-p-tolyl-1,3-dihydro-3-benzazepin-2-one (3k):
1H NMR (400 MHz, CDCl3) δ 7.60 (d, J=8.0 Hz, 1H), 7.43-
7.34 (m, 3H), 7.22-7.17 (m, 4H), 7.11-1.07 (m, 1H), 7.03-6.97
(m, 2H), 6.46 (d, J=7.6 Hz, 2H), 3.80 (dd, J=18.4, 12.0 Hz, 2H),
3.45-3.41 (m, 2H), 2.40 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
169.9 139.7 139.1 136.6 136.1 134.7 133.8 130.3 129.9 129.8 128.9
128.0 127.4 127.3 127.1 126.9 116.8 48.3 42.5 21.4; MS (EI, m/z)
417 [M]þ; HRMS (EI) calcd for C24H20BrNO [M]þ 417.0728,
found 417.0727.
Typical Procedure for the Synthesis of 5-Bromo-3-methyl-4-
p-tolyl-1,3-dihydro-3-benzazepin-2-one (3a). A mixture of 1a
(0.1 mmol), AuBr3 (0.12 mmol), and CH3COOH (0.01 mmol)
in 4 mL of anhydrous THF was heated at 120 °C in a sealed tube
under argon protection for 5 h. After the reaction was cooled to
ambient temperature, the solvent was removed under reduced
pressure, and the residue was purified by a flash column chro-
1
matography to yield 3a as a white solid: H NMR (300 MHz,
CDCl3) δ 7.78-7.75 (m, 1H), 7.40-7.25 (m, 7H), 3.73 (s, 2H),
2.68 (s, 3H), 2.40 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 170.2
140.9 139.0 135.8 134.8 134.2 130.2 130.1 129.8 129.5 129.1 127.5
127.3 127.2 114.6 42.5 34.5 21.4; MS (EI, m/z) 341 [M]þ; HRMS
(EI) calcd for C18H16BrNO [M]þ 341.0415, found 341.0413.
5-Bromo-3-butyl-4-p-tolyl-1,3-dihydro-3-benzazepin-2-one (3c):
1H NMR (400 MHz, CDCl3) δ 7.76-7.70 (m, 1H), 7.40-7.37
(m, 4H), 7.32-7.30 (m, 1H), 7.26 (s, 1H), 7.24 (s, 1H), 3.94-3.87
(m, 1H), 3.70 (dd, J=16.8, 12.4 Hz, 2H), 2.57-2.51 (m, 1H),
2.42 (s, 3H), 1.20-1.03 (m, 2H), 0.89-0.79 (m, 2H), 0.63 (t, J=
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.7 140.0 138.9
135.9 135.2 134.2 130.2 129.8 129.7 128.9 127.4 127.2 44.9 42.7
29.7 21.4 19.3 13.5; MS (EI, m/z) 383 [M]þ; HRMS (EI) calcd for
C21H22BrNO [M]þ 383.0885, found 383.0886.
5-Bromo-3-butyl-4-m-tolyl-1,3-dihydro-3-benzazepin-2-one (3d):
1H NMR (400 MHz, CDCl3) δ 7.77-7.72 (m, 1H), 7.40-7.37
(m, 4H), 7.32-7.30 (m, 1H), 7.26(s, 1H), 7.24(s, 1H), 3.94-3.87
(m, 1H), 3.70 (dd, J=16.4, 12.0 Hz, 2H), 2.57-2.51 (m, 1H),
2.41 (s, 3H), 1.21-1.01 (m, 2H), 0.89-0.78 (m, 2H), 0.62 (t, J=
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.7 140.1 138.1
137.1 135.9 135.1 130.2 129.8 129.7 128.1 127.4 127.2 116.2 44.9
42.7 29.7 21.0 19.3 14.2; MS (EI, m/z) 383 [M]þ; HRMS (EI)
calcd for C21H22BrNO [M]þ 383.0885, found 383.0883.
Acknowledgment. We gratefully acknowledge financial
support from the National Natural Science Foundation of
China (Grant Nos. 20721003 and 20872153), International
Collaboration Projects (Grant No. 20720102040), the 863
Hi-Tech Program of China (Grant Nos. 2006AA020602 and
2006AA10A201), and National S&T Major Projects (Nos.
2009ZX09501-001 and 2009ZX09501-010).
5-Bromo-3-butyl-4-o-tolyl-1,3-dihydro-3-benzazepin-2-one (3e):
1H NMR (400 MHz, CDCl3) δ 7.79-7.71 (m, 1H), 7.48 (d, J=
7.6 Hz, 1H),7.41-7.27 (m, 6H), 3.80-3.71 (m, 3H), 2.72-2.65
(m, 1H), 2.28 (s, 3H), 1.24-1.05 (m, 2H), 0.94-0.83 (m, 2H),
0.63 (t, J=7.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 169.3
139.9 137.1 135.6 135.5 134.6 132.1 130.7 130.2 129.7 129.2 127.5
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Supporting Information Available: Copies of H and 13C
NMR spectra for all products, and crystallographic information
files for compounds 2a and 3a. This material is available free of
charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 11, 2010 3677