Facile Access to 1,5-Benzodiazepines via Amine-Promoted (4+3) Annulations of δ-Acetoxy Allenoates with o -Diaminobenzenes under Mild Conditions

Article abstract of DOI:10.1055/s-0037-1609347

An amine-promoted (4+3) annulation of δ-acetoxy allenoate with o -diaminobenzene is reported, providing a facile access to 1,5-benzodiazepine. This method features wide reaction scope, mild conditions, and readily available starting materials. The cascade reaction involves aza-Michael addition of o -diaminobenzene to allenoate, elimination of acetate group, and subsequent 1,6-aza-Michael addition.

Full text of DOI:10.1055/s-0037-1609347

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© Georg Thieme Verlag Stuttgart · New York
2018, 29, A–E
letter
A
en
Y.-F. Wang et al.
Letter
Synlett
Facile Access to 1,5-Benzodiazepines via Amine-Promoted (4+3)
Annulations of δ-Acetoxy Allenoates with o-Diaminobenzenes
under Mild Conditions
Yi-Fan Wanga
X
X
X
X
Cheng-Yu Heb
Longlei Houa
Ping Tian*b,c
Guo-Qiang Linb,c
Xiaofeng Tong*a
DIPEA
(1.2 equiv)
OAc
H
+
0
0
0
0
0-
0
0
2
5-
6
1
2
0-
6
6
4
toluene
r.t.,12 h
HN
NH
CO2Et
7
H
H2N
NH2
CO2Et
5-benzodiazepines
23 examples, 34–87% yield
a Key Laboratory for Advanced Materials and Institute of Fine
Chemicals, East China University of Science and Technology,
130 Meilong Road, Shanghai, 200237, P. R. of China
tongxf@ecust.edu.cn
b Key Laboratory of Synthetic Chemistry of Natural Substances,
Center for Excellence in Molecular Synthesis, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Road, Shanghai 200032, P. R. of China
tianping@sioc.ac.cn
c Innovation Research Institute of Traditional Chinese Medicine
(IRI), Shanghai University of Traditional Chinese Medicine,
1200 Cailun Road, Shanghai 201203, P. R. of China
tianping@shutcm.edu.cn
Received: 20.01.2018
Accepted after revision: 20.02.2018
Published online: 23.03.2018
pounds or 1,3-dicarbonyl compounds represent two
straightforward strategies and may be the most common
methods (Scheme 1, a).7 However, these two methods suf-
fer from the requirement of acid catalyst and relatively
higher reaction temperature. While the three-component
reaction between o-diaminobenzene, aromatic aldehyde,
and methyl acetoacetate has also emerged as a powerful
method for the construction of benzodiazepine derivative,
alkyl aldehydes are not tolerated, thus severely limiting the
reaction scope (Scheme 1, b).8 To complement the above-
mentioned limitations, we herein report a new strategy to-
ward 1,5-benzodiazepine synthesis via the (3+4) annula-
tion of δ-acetoxy allenoate with o-diaminobenzene
(Scheme 1, c). This method features mild reaction condi-
tions, simple experimental operation as well as wide sub-
strate scope.
Recently, our group has demonstrated that δ-acetoxy al-
lenoate 1 is a highly active 3C-atom component, which
readily undergoes (3+n) annulations with various 1,n-
bisnucleophiles (n = 2, 3) under the Lewis base catalysis.9
Thus, we envisioned that, in view of its 1,4-bisnucleophilic-
ity, o-diaminobenzene 2 might also be a suitable four-atom
component for the (3+4) annulation with allenoate 1. To
verify this hypothesis, the reaction of allenoate 1a and o-di-
aminobenzene 2a was conducted with the assistance of
DABCO (20 mol%) and K2CO3 (1.2 equiv) in toluene at room
temperature. To our delight, the desired (3+4) annulation
product 3aa was isolated in 73% yield (Table 1, entry 1). The
structural assignment was initially supported by NMR and
DOI: 10.1055/s-0037-1609347; Art ID: st-2018-w0046-l
Abstract An amine-promoted (4+3) annulation of δ-acetoxy allenoate
with o-diaminobenzene is reported, providing a facile access to 1,5-
benzodiazepine. This method features wide reaction scope, mild condi-
tions, and readily available starting materials. The cascade reaction in-
volves aza-Michael addition of o-diaminobenzene to allenoate, elimina-
tion of acetate group, and subsequent 1,6-aza-Michael addition.
Key words 1,5-benzodiazepine, annulation, allenoate, diamino-
benzene, catalyst-free
Nitrogen-containing heterocycles always receive much
attention in both of organic synthesis and pharmaceutical
communities. In this context, benzodiazepine derivatives
possess a unique seven-membered heterocycles, which ex-
hibit a wide range of biological activities,1 such as anti-
biotic,2 anticancer,3 and antiviral (HIV) activities.4 More-
over, benzodiazepines are useful starting materials for the
construction of other heterocycles, such as triazole and
oxadiazole.5 Indeed, benzodiazepine skeleton has been rec-
ognized as the privileged medicinal structure, which was
initially coined by Merck scientists and becomes a well-
accepted and popular concept.6
Therefore, a lot of efficient methods have been devel-
oped for the preparation of benzodiazepine derivatives.
Among these contributions, the condensation reactions of
o-diaminobenzenes with α,β-unsaturated carbonyl com-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

B
Y.-F. Wang et al.
Letter
Synlett
HRMS, and later corroborated by X-ray crystallography of
product 3ga (Figure 1).10
Our previous works have pointed out that the reactivity
of allenoate 1 strongly depends on the nature of the em-
ployed catalyst. Thus, catalysts PPh3 and DMAP were then
tested with the hope that something different would be
disclosed.9 However, these two catalysts under the other-
R1
N
O
R1
R
R
N
NH2
NH2
H
R
acid catalyst
+
or
or
(a)
R1
high temperature
Figure 1 The x-ray structure of 3ga
O
O
N
R1
N
R
wise identical conditions still gave 3aa, albeit in inferior
yields (Table 1, entries 2 and 3). These results led us to real-
ize that the (3+4) annulation toward product 3aa might not
involve the Lewis base catalyst. Indeed, a slightly higher
yield of 3aa (76%) was obtained when none of them was
used (Table 1, entry 4). On the basis of these results, base
additive was further screened, which rapidly disclosed that
organic base DIPEA was the best one, affording product 3aa
in as high as 93% isolated yield (Table 1, entries 5–8).
O
O
NH2
NH2
OMe
catalyst
(b)
(c)
+
+
+
HN
Ar
NH
O
ArCHO
OMe
OAc
NH2
NH2
catalyst-free
R
HN
NH
•
O
ambient
temperature
After establishing the optimal reaction conditions, we
turned our attention to exploring the substrate scope with
respective to allenoate partner by reacting with 2a.11 As
shown in Scheme 2, the (3+4) annulation smoothly
occurred under these mild conditions and 1,5-benzodiaze-
pine derivatives were generally obtained in good to excel-
lent yields. A wide range of aryl groups at δ-position of
allenoate 1, including 4-MeOC6H4, 4-MeC6H4, 4-i-PrC6H4,
4-FC6H4, 4-ClC6H4, 4-BrC6H4, 4-CNC6H4, 2-BrC6H4, 3-BrC6H4,
3-MeC6H4, were well tolerated. Significantly, these cases
with either electron-rich or electron-poor phenyl groups all
afforded good yields (3aa–ha). For the case of 1i with a 2-
BrC6H4 substitution, the (3+4) annulation could also take
place smoothly to deliver product 3ia in 81% yield, indicat-
ing that the steric hindrance had little effect on the reaction
efficiency. The reaction was further extended to allenoate
with furan or thiophene substitution, affording products
3la and 3ma in 34% and 87% yields, respectively. Allenoates
1n with a 1-naphthyl substituent and 1o with a styryl
group were also suitable substrates, and the corresponding
products 3na and 3oa were obtained in good yields. Nota-
bly, the reactions of allenoates 1p and 1q bearing an alkyl
group also worked well. In addition, the simplest allenoate
1r was also examined. Unfortunately, product 3ra was iso-
lated only in 45% yield, which might attribute to its higher
reactivity to produce some unidentified side products.
We then moved on to investigate the substrate scope of
o-diaminobenzene (Scheme 3).11 It was found that diamino-
benzenes 2b–e with either electron-donating or electron-
CO2Et
R
OEt
R = aryl, alkyl, H
Scheme 1 Synthesis of benzodiazepine on the base of o-diamino-
benzene
Table 1 Reaction Optimization of Allenoate 1a and o-Diaminobenzene
2aa
OAc
catalyst, additives
Ph
+
HN
Ph
NH
•
toluene, 12 h, r.t.
H2N
NH2
E
E
1a (E = CO2Et)
2a
3aa
Entry
Catalyst (20 mol%)
Additives (1.2 equiv)
Yield of 3aa (%)b
1
2
3
4
5
6
7
8
DABCO
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
NaHCO3
Et3N
73
60
13
76
63
46
85
93
PPh3
DMAP
–
–
–
–
–
DIPEA
a Reaction conditions: To a solution of 2a (0.2 mmol) and base additives
(0.24 mmol) in toluene (2 mL) was slowly added the solution of 1a
(0.24 mmol) in toluene (2 mL) at room temperature.
b Yield of isolated product after column chromatography.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

C
Y.-F. Wang et al.
Letter
Synlett
OAc
DIPEA (1.2 equiv)
toluene 12 h, r.t.
R
+
HN
NH
•
H2N
NH2
CO2Et
CO2Et
R
1
2a
3
3ba (X = OMe): 84% yield
3ca (X = Me): 80% yield
3da (X = iPr): 86% yield
3ea (X = F): 86% yield
3fa (X = Cl): 77% yield
3ga (X = Br): 84% yield
3ha (X = CN): 72% yield
HN
NH
HN
HN
NH
NH
HN
NH
HN
NH
CO2Et
CO2Et
CO2Et
CO2Et
X
CO2Et
X
Br
3ia: 81% yield
X
3ja (X = Br): 86% yield
3ka (X = Me): 85% yield
3la (X = O): 34% yield
3ma (X = S): 87% yield
3aa: 93% yield
HN
NH
HN
NH
CO2Et
CO2Et
HN
NH
HN
HN
NH
NH
CO2Et
CO2Et
3pa: 82% yield
CO2Et
3ra: 45% yield
Bn
3qa: 85% yield
3na: 74% yield
3oa: 85% yield
Scheme 2 The reaction scope with respective to allenoate 1
withdrawn groups were compatible with this (3+4) annula-
tion, giving products 3ab–ae in 34–71% yields. Naphtha-
lene-2,3-diamine 2f also reacted well with allenoate 1a to
deliver product 3af in 51% yield.
1,6-addition to give enolate C. Finally, product 3 was result-
ed in via a deprotonation process, thus furnishing a (3+4)
annulation.
DIPEA
(1.2 equiv)
– AcO–
2
OAc
Ar
1
H2N
AcO
NH
Ar
H2N
R
NH
Ph
base
+
E
HN
Ph
NH
toluene
12 h, r.t.
E
–
H2N
NH2
CO2Et
R
CO2Et
A
B
1a
2
3
X
X
3ab (X = Me): 70%
3ac (X = F): 71%
3ad (X = Cl): 45%
3ae (X = Br): 34%
3af
51% yield
+
N
H
HN
Ph
NH
HN
Ph
NH
H
H
N
O–
OEt
HN
R
NH
CO2Et
CO2Et
CO2Et
R
3
C
Scheme 3 Substrate scope with respective to o-diaminobenzene
Scheme 4 A plausible mechanism
According to these results and our previous works, we
proposed a plausible mechanism for the observed catalyst-
free (3+4) annulation (Scheme 4). Due to the intramolecular
H-bond interaction, the NH group of o-diaminobenzene
seems to be readily deprotonated, thus promoting the
Michael addition with allenoate 1.12 As a result, intermedi-
ate A is formed, which undergoes elimination of acetate
group to afford diene intermediate B. The fact that interme-
diate B could not be detected for all of the cases might im-
ply that B would be able to undergo rapid intramolecular
In summary, we have developed a new strategy toward
1,5-benzodiazepine synthesis via (3+4) annulations be-
tween δ-acetoxy allenoates with o-diaminobenzenes. The
(3+4) annulation might proceed via a sequence including
aza-Michael addition of diaminobenzene to allenoate, elim-
ination of acetate group, and subsequent 1,6-addition. This
method features readily available starting material, mild re-
action conditions, high reaction efficiency, as well as wide
substrate scope.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

D
Y.-F. Wang et al.
Letter
Synlett
Funding Information
Zhou, Q.-L. Org. Lett. 2017, 19, 3668. (e) Zhang, Y.; Tong, X. Org.
Lett. 2017, 19, 5462. (f) Gu, Y.; Li, F.; Hu, P.; Liao, D.; Tong, X. Org.
Lett. 2015, 17, 1106.
Financial support was generously provided by the 973 Program
(2015CB856600), NSFC (21472042, 21772016, 21572251, 21572253),
and the Collaborative Innovation Center of Chemical Science and En-
(10) CCDC 1816325 contains the supplementary crystallographic
data for 3ga. The data can be obtained free of charge from The
gineering (Tianjin).
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Cambridge
www.ccdc.cam.ac.uk/getstructures.
(11) Acetoxy Allenoates 1 and o-Diaminobenzenes 2
Crystallographic
Data
Centre
via
Acknowledgment
To a 10 mL vial were added o-diaminobenzene 2 (0.2 mmol, 1.0
equiv), DIPEA (0.24 mmol, 1.2 equiv), and toluene (2 mL), fol-
lowed by the slow addition of a solution of δ-acetoxy allenoate
1 (0.24 mmol,1.2 equiv) in toluene (2 mL). The solution was
stirred for 12 h at room temperature. The reaction mixture was
concentrated under reduced pressure, and the residue was puri-
fied by silica gel column chromatography using petroleum ether
and ethyl acetate (30:1 to 15:1 v/v) as the eluent to give the cor-
responding annulations product 3.
Undergraduate students from SIOC, SHUTCM, and ECUST are
acknowledged for their helpful contribution. Authors thank Jie Sun
(SIOC) for X-ray crystallographic analysis and all the reviewers for
their constructive remarks.
Supporting Information
Ethyl
(Z)-2-{4-(4-Isopropylphenyl)-1,3,4,5-tetrahydro-2H-
Supporting information for this article is available online at
benzo[b][1,4]diazepin-2-ylidene}acetate (3da)
https://doi.org/10.1055/s-0037-1609347.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
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Yellow solid, 86% yield; mp 70–72 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.26 (s, 1 H), 7.26 (d, J = 8.2 Hz, 2 H), 7.20 (d, J = 8.2
Hz, 2 H), 6.99–6.93 (m, 2 H), 6.92–6.85 (m, 1 H), 6.76–6.72 (m, 1
H), 4.79 (dd, J = 9.6, 3.8 Hz, 1 H), 4.64 (s, 1 H), 4.23–4.06 (m, 2
H), 3.66 (br s, 1 H),2.90 (hept, J = 6.9 Hz, 1 H), 2.72 (dd, J = 13.8,
9.6 Hz, 1 H), 2.49 (ddd, J = 13.8, 3.8, 1.3 Hz, 1 H), 1.34–1.17 (m, 9
H). 13C NMR (100 MHz, CDCl3): δ = 170.28, 158.84, 148.67,
142.39, 137.83, 129.65, 126.80, 125.98, 124.91, 122.48, 121.35,
120.70, 83.95, 64.84, 58.79, 40.39, 33.76, 23.94, 23.91, 14.53. IR
(KBr): 3853, 3336, 2960, 2929, 2870, 1734, 1654, 1616, 1560,
References and Notes
(1) (a) Randall, O.; Kappel, B. In Benzodiazepines; Garattini, S.;
Mussini, E.; Randall, L. O., Eds.; Raven Press: New York, 1973, 27.
(b) Schütz, H. In Benzodiazepines; Springer: Heidelberg, 1982.
(2) Knabe, J.; Büch, H. P.; Bender, S. Arch. Pharm. 1995, 328, 59.
(3) Atwal, K. S.; Bergey, J. L.; Hedberg, A.; Moreland, S. J. Med. Chem.
1987, 30, 635.
1540, 1507, 1480, 1437, 1364, 1286, 1266, 1246, 1157, 1117,
(4) Di Braccio, M.; Grossi, G.; Roma, G.; Vargiu, L.; Mura, M.;
Marongiu, M. E. Eur. J. Med. Chem. 2001, 36, 935.
(5) (a) Aversa, M. C.; Ferlazzo, A.; Giannetto, P.; Kohnke, F. H. Syn-
thesis 1986, 230. (b) Chimirri, A.; Grasso, S.; Ottana, R.; Romeo,
G.; Zappala, M. J. Heterocycl. Chem. 1990, 27, 371.
1095, 1051, 829 cm–1. HRMS (ESI): m/z calcd for C22H27N2O2
:
+
351.2067; found: 351.2067 [M + H]+.
Ethyl
(Z)-2-{4-(4-Cyanophenyl)-1,3,4,5-tetrahydro-2H-
benzo[b][1,4]diazepin-2-ylidene}acetate (3ha)
Yellow solid, 72% yield; mp 60–62 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.16 (s, 1 H), 7.66–7.60 (m, 2 H), 7.55–7.50 (m, 2 H),
7.03–6.92 (m, 3 H), 6.83–6.79 (m, 1 H), 5.00–4.92 (m, 1 H), 4.43
(s, 1 H), 4.21–4.04 (m, 2 H), 3.73 (s, 1 H), 2.73 (dd, J = 13.8, 4.7
Hz, 1 H), 2.49 (dd, J = 13.9, 7.0 Hz, 1 H), 1.26 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 169.98, 157.03, 149.30, 137.66,
132.43, 130.48, 127.12, 125.09, 122.49, 122.38, 120.97, 118.63,
111.61, 85.04, 64.57, 58.93, 39.37, 14.44. IR (neat): 3629, 3567,
3343, 3057, 2980, 2931, 2228, 1734, 1653, 1616, 1559, 1541,
(6) (a) Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.;
Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D. F.;
Anderson, P. S. J. Med. Chem. 1988, 31, 2235. (b) Patchett, A. A.;
Nargund, R. P. Annu. Rep. Med. Chem. 2000, 35, 289. (c) Triggle,
D. J. Cell. Mol. Neurobiol. 2003, 23, 293. (d) Poupaert, J.; Carato,
P.; Colacino, E. Curr. Med. Chem. 2005, 12, 877.
(7) For the selected examples, see: (a) Nardi, M.; Cozza, A.; Maiuolo,
L.; Oliverio, M.; Procopio, A. Tetrahedron Lett. 2011, 52, 4827.
(b) Aversa, M. C.; Ferlazzo, A.; Gionnetto, P.; Kohnke, F. H. Syn-
thesis 1986, 230. (c) Zhang, X. Y.; Xu, J. X.; Jin, S. Chin. J. Chem.
1999, 17, 404. (d) Yadav, J. S.; Reddy, B. V. S.; Praveenkumar, S.;
Nagaiah, K.; Lingaiah, N.; Saiprasad, P. S. Synthesis 2004, 901.
(e) Jamatia, R.; Gupta, A.; Dam, B.; Sahab, M.; Pal, A. K. Green
Chem. 2017, 19, 1576. (f) Gharib, A.; Jahangir, M.; Scheeren, J.
W. Synth. Commun. 2013, 43, 309. (g) Vaddula, B. R.; Varma, R.
S.; Leazer, J. Tetrahedron Lett. 2013, 54, 1538. (h) Ding, Z.-Y.;
Chen, F.; Qin, J.; He, Y.-M.; Fan, Q.-H. Angew. Chem. Int. Ed. 2012,
51, 5706.
(8) (a) Sarkar, S.; Deka, J. K. R.; Hazra, J. P.; Khan, A. T. Synlett 2013,
24, 2601. (b) Sotoca, E.; Allais, C.; Constantieux, T.; Rodriguez, J.
Org. Biomol. Chem. 2009, 7, 1911. (c) Lal, M.; Basha, R. S.; Sarkar,
S.; Khan, A. T. Tetrahedron Lett. 2013, 54, 4264.
(9) (a) Hu, J.; Dong, W.; Wu, X.-Y.; Tong, X. Org. Lett. 2012, 14, 5530.
(b) Wang, D.; Tong, X. Org. Lett. 2017, 19, 6392. (c) Zhou, W.; Ni,
C.; Chen, J.; Wang, D.; Tong, X. Org. Lett. 2017, 19, 1890. (d) Ni,
C.; Chen, J.; Zhang, Y.; Hou, Y.; Wang, D.; Tong, X.; Zhu, S.-F.;
1501, 1437, 1405, 1364, 1284, 1267, 1233, 1159, 1118, 1095,
+
1048, 833 cm–1
.
HRMS (ESI): m/z calcd for C20H20N3O2
:
334.1550; found: 334.1550 [M + H]+.
Ethyl (Z)-2-{4-Methyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]dia-
zepin-2-ylidene}acetate (3pa)
Yellow liquid, 82% yield. 1H NMR (400 MHz, CDCl3): δ = 10.13 (s,
1 H), 6.91–6.75 (m, 3 H), 6.71–6.64 (m, 1 H), 4.61 (s, 1 H), 4.08
(q, J = 7.1 Hz, 2 H), 3.88–3.76 (m, 1 H), 3.17 (br s, 1 H), 2.40 (dd,
J = 13.8, 4.4 Hz, 1 H), 2.15 (dd, J = 13.8, 7.0 Hz, 1 H), 1.26–1.17
(m, 6 H).13C NMR (100 MHz, CDCl3): δ = 170.11, 159.16, 137.87,
130.34, 124.67, 122.27, 121.67, 120.90, 84.25, 58.79, 55.83,
39.31, 23.40, 14.54. IR (neat): 3347, 2973, 2927, 1648, 1616,
1588, 1498, 1447, 1364, 1307, 1274, 1232, 1159, 1115, 1095,
+
1044, 916, 784 cm–1. HRMS (ESI): m/z calcd for C14H19N2O2
:
247.1441; found: 247.1440 [M + H]+.
Ethyl (Z)-2-{4-Benzyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]dia-
zepin-2-ylidene}acetate (3qa)
Yellow solid, 85% yield; mp 106–108 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.13 (s, 1 H),7.31–7.12 (m, 5 H), 6.89–6.75 (m, 3 H),
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

E
Y.-F. Wang et al.
Letter
Synlett
6.63–6.56 (m, 1 H), 4.64 (s, 1 H),4.16–4.00 (m, 2 H),3.94–3.82
(m, 1 H), 3.23 (br s, 1 H), 2.82–2.67 (m, 2 H), 2.42 (dd, J = 13.7,
4.7 Hz, 1 H), 2.23 (dd, J = 13.8, 7.2 Hz, 1 H), 1.21 (t, J = 7.1 Hz, 3
H). 13C NMR (100 MHz, CDCl3): δ = 170.08, 158.92, 137.89,
137.57, 130.94, 129.27, 128.74, 126.70, 124.69, 122.15, 121.95,
121.33, 84.32, 62.01, 58.80, 43.31, 37.26, 14.52. IR (neat): 3386,
1618, 1588, 1505, 1404, 1365, 1332, 1285, 1262, 1225, 1158,
1123, 1095, 1065, 1039, 1004, 790 cm–1. HRMS (ESI): m/z calcd
for C20H23N2O2+: 323.1754; found: 323.1757 [M + H]+.
Ethyl (Z)-2-{7,8-Dibromo-4-phenyl-1,3,4,5-tetrahydro-2H-
benzo[b][1,4]diazepin-2-ylidene}acetate (3ae)
Yellow solid, 34% yield; mp 60–62 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.17 (s, 1 H), 7.35–7.16 (m, 5 H), 7.13 (s, 1 H), 6.94
(s, 1 H), 4.72 (dd, J = 9.1, 3.6 Hz, 1 H), 4.57 (s, 1 H), 4.16–3.99 (m,
2 H), 3.69 (br s, 1 H), 2.62 (dd, J = 14.0, 9.1 Hz, 1 H), 2.48 (dd, J =
14.0, 3.7 Hz, 1 H), 1.20 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz,
CDCl3): δ = 170.23, 157.97, 143.54, 137.84, 131.84, 130.32,
128.03, 125.10, 122.55, 122.08, 121.74, 121.01, 84.72, 64.57,
58.98, 39.93, 14.61. IR (neat): 3420, 3132, 1717, 1653, 1617,
Ethyl (Z)-2-{1,3,4,5-Tetrahydro-2H-benzo[b][1,4]diazepin-2-
ylidene}acetate (3ra)
1559, 1540, 1507, 1490, 1457, 1404, 1300, 1239, 1160, 1066,
Yellow solid, 45% yield; mp 56–58 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.22 (s, 1 H), 6.88–6.79 (m, 2 H), 6.76–6.70 (m, 1 H),
6.67–6.59 (m, 1 H), 4.61 (s, 1 H), 4.08 (q, J = 7.1 Hz, 2 H), 3.60–
3.52 (m, 2 H), 3.13 (br s, 1 H), 2.49–2.41 (m, 2 H), 1.21 (t, J = 7.1
Hz, 3 H).13C NMR (100 MHz, CDCl3): δ = 170.34, 160.98, 138.16,
128.87, 124.60, 122.64, 120.60, 119.79, 83.32, 58.81, 48.70,
33.76, 14.55. IR (neat): 3386, 1618, 1588, 1505, 1404, 1365,
1332, 1285, 1262, 1225, 1158, 1123, 1095, 1065, 1039, 1004,
790 cm–1. HRMS (ESI): m/z calcd for C13H17N2O2+: 233.1285;
found: 233.1284 [M + H]+.
1010, 700 cm–1. HRMS (ESI): m/z calcd for C19H19 Br2N2O2
:
+
464.9808; found: 464.9806 [M + H]+.
Ethyl
(Z)-2-{4-Phenyl-1,3,4,5-tetrahydro-2H-naphtho[2,3-
b][1,4]diazepin-2-ylidene}acetate (3af)
Yellow solid, 51% yield; mp 65–67 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.43 (s, 1 H), 7.71–7.59 (m, 2 H), 7.45–7.23 (m, 8 H),
7.16 (s, 1 H), 4.85 (dd, J = 9.1, 4.6 Hz, 1 H), 4.67 (s, 1 H), 4.25–
4.11 (m, 2 H), 3.96 (s, 1 H), 2.70 (dd, J = 13.8, 9.1 Hz, 1 H), 2.60
(dd, J = 13.8, 4.6 Hz, 1 H), 1.30 (t, J = 7.1 Hz, 3 H). 13C NMR (100
MHz, CDCl3): δ = 170.24, 158.02, 144.63, 137.89, 132.05, 131.81,
129.99, 128.83, 128.00, 126.73, 126.15, 125.77, 125.25, 124.32,
119.10, 116.58, 85.17, 64.80, 59.00, 39.54, 14.54. IR (KBr): 3629,
3619, 3600, 3587, 3567, 3546, 3528, 3503, 3355, 3056, 2977,
2926, 1734, 1717, 1684, 1654, 1616, 1576, 1559, 1541, 1522,
1507, 1490, 1474, 1457, 1437, 1364, 1286, 1248, 1185, 1156,
Ethyl (Z)-2-{7,8-Dimethyl-4-phenyl-1,3,4,5-tetrahydro-2H-
benzo[b][1,4]diazepin-2-ylidene}acetate (3ab)
Yellow solid, 70% yield; mp 100–102 °C. 1H NMR (400 MHz,
CDCl3): δ = 10.18 (s, 1 H), 7.41–7.22 (m, 5 H), 6.76 (s, 1 H), 6.55
(s, 1 H), 4.80 (dd, J = 9.2, 4.0 Hz, 1 H), 4.58 (s, 1 H), 4.23–4.05 (m,
2 H), 3.56 (br s, 1 H), 2.67 (dd, J = 13.7, 9.2 Hz, 1 H), 2.50 (ddd, J =
13.7, 4.0, 1.1 Hz, 1 H), 2.17 (s, 6 H), 1.27 (t, J = 7.1 Hz, 3 H). 13C
NMR (100 MHz, CDCl3): δ = 170.29, 158.92, 145.05, 135.43,
133.22, 129.69, 128.73, 127.83, 127.41, 126.05, 123.53, 121.90,
83.54, 65.16, 58.73, 40.37, 19.10, 18.74, 14.55. IR (KBr): 3376,
3276, 3064, 2973, 2906, 2888, 2859, 1654, 1609, 1513, 1482,
1451, 1428, 1365, 1310, 1281, 1242, 1199, 1160, 1129, 1094,
1096, 1047, 872, 788 cm–1
23H23N2O2+: 359.1754; found: 359.1753 [M + H]+.
. HRMS (ESI). m/z calcd for
C
(12) (a) Li, F.; Chen, J.; Hou, Y.; Li, Y.; Wu, X.-Y.; Tong, X. Org. Lett.
2015, 17, 5376. (b) Ni, C.; Yuan, Y.; Zhang, Y.; Chen, J.; Wang, D.;
Tong, X. Org. Biomol. Chem. 2017, 15, 4807. (c) Sabbasani, V. R.;
Mamidipalli, P.; Lu, H.; Xia, Y.; Lee, D. Org. Lett. 2013, 15, 1552.
(d) Zhao, Y.; Wang, Y.; Gu, Z.; Wang, Z. Org. Biomol. Chem. 2017,
15, 4014.
1048, 988, 950, 897 cm–1
21H25N2O2+: 337.1911; found: 337.1910 [M + H]+.
. HRMS (ESI): m/z calcd for
C
© Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E