Lewis acid-promoted three-component reactions of propargylic alcohols with 2-butynedioates and secondary amines

Article abstract of DOI:10.1021/jo2016407

We report herein a three-component reaction of propargylic alcohols with 2-butynedioates and secondary amines, which furnished functionalized dihydroazepines. In the cases where benzylmethylamine and benzyl-i-propylamine were used as the secondary amine, the reaction afforded 2,5-dihydro-1H-pyrroles and 2,3-dihydro-1H-pyrroles, respectively, as the major product along with the desired dihydroazepines. The reaction mode depends on the electronic and steric effect of the substitutents on the secondary amines used. A tentative mechanism for this cascade process is postulated. The key intermediate is ascribed to 1,3,4-pentatrien-1-amine, which is formed by trapping the in situ generating allenic carbocation with enamine. Because of the reactivity of 1,3,4-pentatrien-1-amine formed, different products were thus formed.

Full text of DOI:10.1021/jo2016407

Article
pubs.acs.org/joc
Lewis Acid-Promoted Three-Component Reactions of Propargylic
Alcohols with 2-Butynedioates and Secondary Amines
Guangwei Yin, Yuanxun Zhu, Ping Lu,* and Yanguang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
S
* Supporting Information
ABSTRACT: We report herein a three-component reaction
of propargylic alcohols with 2-butynedioates and secondary
amines, which furnished functionalized dihydroazepines. In
the cases where benzylmethylamine and benzyl-i-propylamine
were used as the secondary amine, the reaction afforded
2,5-dihydro-1H-pyrroles and 2,3-dihydro-1H-pyrroles, respec-
tively, as the major product along with the desired dihydroazepines. The reaction mode depends on the electronic and steric
effect of the substitutents on the secondary amines used. A tentative mechanism for this cascade process is postulated. The key
intermediate is ascribed to 1,3,4-pentatrien-1-amine, which is formed by trapping the in situ generating allenic carbocation with
enamine. Because of the reactivity of 1,3,4-pentatrien-1-amine formed, different products were thus formed.
INTRODUCTION
■
Dihydroazepine and its analogues represent an important class
of heterocyclic compounds because of their bioactivities and
pharmaceutical applications.1Three examples of the clinically
used drugs containing the dihydroazepine ring are Imipramine,
Carbamazepine, and Oxcarbazepine. In addition, a number of
natural products contain this structural unit.2 Therefore, a
number of methodologies have been developed for the con-
struction of these heterocyclic seven-membered rings.3 Classical
approaches include the insertion of nitrenes, cyclization of
diene-conjugated nitrile ylides,4 and intramolecular Heck
reaction.5 Recently, transition metal-catalyzed cyclizations,6
Figure 1. Design blueprint for trapping the allenic carbocation.
[4+3] cycloadditions,7 [5+2] cycloadditions,8 and ring-closing
methathesis9 have been reported. The known biological pro-
A detailed description of the proposal is shown in Figure 1.
perties and the huge potential in drug discovery of these hetero-
cyclic compounds still need the development of facile and
efficient methodologies for their selective and diverse synthesis.
Because of the easy generation and the prosperous reactions,
allenes have attracted much attention in organic synthesis,
especially in the synthesis of heterocycles and carbocycles with
high complexity.10 A practical way to form allenes is using
suitable nucleophiles to trap the allenic carbocation intermedi-
ates, which could be generated in situ by the Meyer−Schuster
rearrangement of propargylic alcohols.11 Either Brønster acids or
Lewis acids could efficiently catalyze this rearrangement. Using
this strategy, a number of substituted allenes12 and allenamides13
were synthesized. The substituted indenes,14 methylenecyclobu-
tenes,15 and thiazoles were also constructed via a cascade process
from propargylic alcohols.16
Herein, we report the realization of this goal leading to a
convenient method for the construction of dihydroazepines.
RESULTS AND DISCUSSION
■
To test this new process, we began by choosing 1,1,3-
triphenylprop-2-yn-1-ol (3a) and diethyl 2-(diethylamino)-
maleate17 as the coupling partners. The later was formed in
situ in an exclusive E-configuration by the reaction between
diethyl but-2-ynedioate (1a) and diethylamine (2a). To our
delight, dihydroazepine 4a was constructed in 73% yield when
AlCl3 was used as a catalyst (Table 1, entry 1). The structure of
4a was determined by X-ray single-crystal analysis.18
Enlightened by this result, we optimized the reaction condi-
tions for the formation of 4a, and the results are summarized in
Table 1. When the catalyst was changed to ZnCl2, FeCl3, or
I2, 4a was obtained in a yield of 41, 76, or 49%, respectively
(Table 1, entries 2−4). Boron trifluoride etherate gave the best
In our efforts to develop a cascade process, we wondered
whether the allenic carbocation generated in situ from
propargylic alcohols could be trapped by enamine to give a
cascade reaction product. The enamine bearing two ester
groups was derived from butynedioate and a secondary amine
and is believed to be able to decrease its nucleophilicity.
Received: August 9, 2011
Published: September 23, 2011
© 2011 American Chemical Society
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a
yield among these catalysts (Table 1, entries 1−5). After the
loading amount of boron trifluoride etherate had been
decreased to 10 mol %, only a trace amount of 4a was
detected by thin layer chromatography (Table 1, entry 6).
Similarly, after the amount of FeCl3 had been decreased to 20
mol %, 4a was isolated in a relatively lower yield in comparison
with the use of an equivalent molar amount of FeCl3 (Table 1,
entries 3 and 7). Changing the solvent to toluene, acetonitrile
(CH3CN), or tetrahydrofuran (THF) also decreased the yield
of 4a (Table 1, entries 8−10). N,N-Dimethylformamide
(DMF) did not work for this transformation (Table 1, entry
11). Either increasing or decreasing the reaction temperature
influenced the isolated yield (Table 1, entries 12 and 13). The
presence of a 4 Å molecular sieve would be beneficial for
the reaction (Table 1, entry 14). Thus, the optimized reaction
condition was established (Table 1, entry 5).
As the next step, we tested the substrate scope. As shown in
Figure 2, propargylic alcohols, synthesized from para-
substituted phenylacetylenes and symmetrical benzophenones,
afforded the corresponding dihydroazepine derivatives 4b−e in
good yields (76−85%). The effect of the substituent on the
para position of phenyl acetylene was not apparent no matter
if it was electron-withdrawing (4d) or electron-donating
(4e) . A propargylic alcohol derived from aliphatic alkyne
and benzophenone produced 4f in 55% yield, while
1,1-diphenylprop-2-yn-1-ol afforded 4g in 40% yield only.
Table 1. Screening for Reaction Conditions
time
(h)
yield
b
entry
catalyst
solvent
temp
(%)
1
2
3
4
5
6
AlCl3
ZnCl2
FeCl3
I2
DCM
DCM
DCM
DCM
DCM
DCM
reflux
reflux
reflux
reflux
reflux
reflux
1
1
1
2
1
8
73
41
76
49
BF3·Et2O
BF3·Et2O (10 mol
%)
83
trace
7
FeCl3 (20 mol %)
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
DCM
toluene
CH3CN
THF
reflux
50 °C
50 °C
50 °C
50 °C
80 °C
rt
12
1
40
8
72
9
1
69
10
11
12
13
1
12
DMF
1
trace
78
DCE
1
DCM
DCM
5
60
c
14
reflux
1
65
a
Reaction conditions: 1a (1 mmol), 2a (1 mmol), solvent (3 mL), rt,
10 min; 3a (1 mmol), 4 Å molecular sieves (0.4 g), catalyst (1 mmol).
b
c
Isolated yield. Without 4 Å molecular sieves.
Figure 2. Structures of dihydroazepines 4b−q and their yields.
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A propargylic alcohol derived from 4,4′-dimethylbenzophenone
or fluorenone reacted with enamine generated from dimethyl
but-2-ynedioate (1b) and diethylamine (2a) furnished 4h and
4i in 71 and 53% yields, respectively. Propargylic alcohol derived
from unsymmetrical ketone also worked for the reaction to give
4j in 60% yield. An acetophenone-derived alcohol gave 4k
in a slightly lower yield. The enamine component was formed
in situ for this cascade reaction. The formation of diethyl
2-(diethylamino)maleate was confirmed by characterizing the
isolated enamine from the mixture of diethyl but-2-ynedioate
(1a) and diethylamine.19 Dipropylamine (2b), dibutylamine
(2c), dibenzylamine (2d), and cyclic secondary amines, such as
pyrrolidine (2e) and piperidine (2f), also worked well for this
reaction to afford the corresponding products 4l−q in yields
between 64 and 81%.
and 4v (20% yield) (Scheme 3). Other unexpected products
were also isolated when N-benzylpropan-2-amine (2j) was
Scheme 3. Formation of 4u−x, 6, and 7
When morpholine (2g) was used, a highly strained molecule
5 (31% yield)20 was isolated along with the desired product 4r
(34% yield) (Scheme 1). When the reaction temperature was
Scheme 1. Formation of 4r and 5
tested. In this case, 2,3-dihydro-1H-pyrroles 7a (49% yield) and
7b (52% yield) were constructed besides the desired products
4w (23% yield) and 4x (16% yield). Structures of 6b21 and 7a22
were confirmed by X-ray single-crystal diffraction.
In the case where diisobutylamine (2k), a bulky secondary
amine, was used (Scheme 4), we isolated dihydroazepine 4y
Scheme 4. Formation of 4y and 8
increased to 80 °C, however, 4r could be obtained as a major
product. It was noticed by the varied-temperature NMR that
the isolated 5 could be converted to 4r at higher temperatures
(see the Supporting Information).
We also examined the amines with two different alkyl groups,
such as N-benzylethanamine (2h), and obtained the expected
dihydroazepines 4s (59% yield) and 4t (52% yield) (Scheme 2).
Scheme 2. Formation of 4s and 4t
(17% yield) and a ring-opening dienamine 8 (58% yield).23 We
also observed that the resulting dihydroazepine 4y was unstable
and easily underwent hydrolysis in the presence of a trace amount
of water to yield dienamine 8 (see the Supporting Information).
Finally, we examined the enamine24 derived from methyl
propiolate (1c) (Scheme 5) and found that it reacted with 3a to
afford 2,4-dienal 9 in 52% yield. Noteworthy is the fact that
2,4-dienals are useful conjugated carbonyl compounds in organic
synthesis.25
However, benzylmethylamine (2i) afforded 5-methylene-2,5-
dihydro-1H-pyrroles 6a (45% yield) and 6b (56% yield) in
majority except for the desired dihydroazepines 4u (32% yield)
On the basis of these results, we postulated a possible
mechanism for the formation of 4−8 (Scheme 6). Reaction of 1
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and 2 results in the formation of enamine A, which is an
electron-deficient enamine in comparison to an alkylated one
because of the electron withdrawing nature of two ester groups.
A suitably traps the allenic carbocation B that is formed in situ
through the Meyer−Schuster rearrangement of 1,1,3-triphenyl-
prop-2-yn-1-ol (3a) to generate iminium intermediate C with a
β-hydrogen. Subsequent deprotonation of C forms a better-
conjugated intermediate D, possessing a chain of 1,3,4-
pentatrien-1-amine. As electrons flow as indicated in the D
structure, an azomethine ylide E26 is generated. Intramolecular
1,6-Michael addition of E27 gives dihydroazepine ring 4, while
intramolecular 1,4-Michael addition of E forms 2,3-dihydro-1H-
pyrrole ring 7 in the case of N-benzylpropan-2-amine (2e).
When morpholine is used as a substrate, a four-membered ring
5 is obtained via intermediate F, which is the resonance
structure of D. The reactivity of the iminium of F is obvious
because of the inductive effect of the oxygen in the morpholine
ring,28 which results in the formation of 5. 5 is unstable because
of the ring strain. It undergoes ring opening under heat and
regenerates F, which produces the thermodynamically favored
4r. When benzylmethylamine (2d) is used as the substrate, the
nitrogen atom of D nucleophilically attacks the central carbon
of allene to form a zwitterion intermediate G. Intramolecular
migration of the benzyl group of G results in the formation of
2,5-dihydro-1H-pyrrole ring 6. In the case where bulky
diisobutylamine (2f) is used, E can undergo a protonation at
its benzylic position to produce imminium H. Hydrolysis of H
leads to the formation of 8 and isobutyl aldehyde.
Formation of 9 could be understood as shown in Scheme 7.
1,3,4-Trienamine K is formed from 1c, 2a, and 3a through a
Scheme 7. Postulated Mechanism for the Formation of 9
pathway similar to that of the formation of D in Scheme 6.
Compared with enamine D, bearing two electron-withdrawing
groups, I is more electron-rich. Therefore, the central carbon of
allene in K prefers protonation, resulting in the formation of
2,4-dieniminium L, which finally undergoes hydrolysis to form
2,4-dienal 9.
Scheme 5. Formation of Dienal 9
CONCLUSION
■
In conclusion, we developed a one-pot reaction of 2-
butynedioates with secondary amines and propargylic alcohols
in the presence of a Lewis acid. Generally, the reaction
furnished functionalized dihydroazepines with a heterocyclic
Scheme 6. Postulated Mechanism for the Formation of 4−8
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ν 2976, 1741, 1686, 1547, 1445, 1258, 1220, 1088, 1025, 707 cm−1
HRMS (EI) m/z calcd for C34H37NO4 523.2624, found 523.2631.
;
seven-membered ring. In some cases, 2,5-dihydro-1H-pyrrole,
2,3-dihydro-1H-pyrrole, and dienamine were also formed along
with the desired dihydroazepines, depending on the electronic
effect and the steric effect of the secondary amines. A tentative
mechanism for the formation of dihydroazepines and by-
products is discussed, and it involves enamine, allenic
carbocation, 1,3,4-pentatrien-1-amine, and azomethine inter-
mediates. The key intermediate is ascribed to 1,3,4-pentatrien-
1-amine, which is formed by trapping the in situ generating
allenic carbocation with enamine.
Diethyl 1-ethyl-4-(4-fluorophenyl)-7-methyl-6,6-diphenyl-6,7-di-
hydro-1H-azepine-2,3-dicarboxylate (4d): yellow solid; 81% yield;
mp 164−165 °C; 1H NMR (400 MHz, CDCl3) δ 7.42−7.33 (m, 4H),
7.30 (t, J = 7.7 Hz, 2H), 7.21−7.04 (m, 6H), 6.95 (t, J = 8.6 Hz, 2H),
6.02 (s, 1H), 4.65 (q, J = 6.1 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H), 3.88−
3.55 (m, 2H), 3.01−2.55 (m, 2H), 1.29 (t, J = 7.0 Hz, 3H), 1.23−1.12
(m, 6H), 0.78 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
169.6, 166.1,161.6 (d, J = 243 Hz), 148.9, 147.5, 142.1, 142.0 (d, J =
3.1 Hz), 139.9, 132.0, 128.4, 128.0, 127.9, 127.74, 127.66, 126.0 (d, J =
5.3 Hz), 114.6 (d, J = 21.2 Hz), 102.7, 62.7, 61.63, 61.59, 60.2, 53.1,
19.2, 16.1, 13.6, 13.5; IR (KBr) ν 2983, 1735, 1710, 1553, 1504, 1444,
1266, 1219, 1085, 755, 706 cm−1; HRMS (EI) m/z calcd for
C33H34FNO4 527.2472, found 527.2464.
Diethyl 1-ethyl-4-(4-methoxyphenyl)-7-methyl-6,6-diphenyl-6,7-
dihydro-1H-azepine-2,3-dicarboxylate (4e): white solid; 76% yield;
mp 120−121 °C; 1H NMR (400 MHz, CDCl3) δ 7.38−7.26 (m, 6H),
7.21−7.10 (m, 5H), 7.07 (t, J = 6.7 Hz, 1H), 6.80 (d, J = 8.6 Hz, 2H),
6.01 (s, 1H), 4.64 (q, J = 6.2 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H), 3.86−
3.57 (m, 5H), 2.99−2.54 (m, 2H), 1.28 (t, J = 7.0 Hz, 3H), 1.23−1.08
(m, 6H), 0.78 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
169.9, 166.2, 158.3, 149.1, 147.0, 142.3, 140.3, 138.6, 131.2, 128.3,
128.0, 127.8, 127.6, 127.5, 125.9, 125.8, 113.2, 103.2, 62.7, 61.6, 60.1,
55.3, 53.0, 19.2, 16.1, 13.6; IR (KBr) ν 2978, 1735, 1690, 1610, 1547,
1510, 1255, 1219, 1089, 1035, 768 cm−1; HRMS (EI) m/z calcd for
C34H37NO5 539.2672, found 539.2681.
Diethyl 4-butyl-1-ethyl-7-methyl-6,6-diphenyl-6,7-dihydro-1H-
azepine-2,3-dicarboxylate (4f): white oil; 55% yield; 1H NMR
(400 MHz, CDCl3) δ 7.35−7.28 (m, 4H), 7.22−7.15 (m, 1H), 7.13
(t, J = 7.5 Hz, 2H), 7.06−6.98 (m, 3H), 5.95 (s, 1H), 4.47 (q, J = 6.2
Hz, 1H), 4.30−4.20 (m, 1H), 4.16−4.00 (m, 3H), 2.83−2.78 (m, 1H),
2.73−2.61 (m, 1H), 2.48−2.34 (m, 1H), 2.29−2.16 (m, 1H), 1.52−
1.09 (m, 16H), 0.85 (t, J = 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ 169.6, 166.6, 149.4, 145.2, 143.1, 138.3, 129.3, 128.2, 128.1, 128.0,
127.4, 125.75, 125.74, 104.8, 61.4, 61.3, 60.5, 52.3, 38.4, 33.2, 23.0,
18.7, 15.7, 14.1, 13.9, 13.6; IR (film) ν 2956, 1731, 1704, 1549, 1445,
1369, 1256, 1147, 1086, 749, 701 cm−1; HRMS (EI) m/z calcd for
C31H39NO4 489.2879, found 489.2882.
EXPERIMENTAL SECTION
■
General Methods. Infrared spectra were recorded with a FTIR
1
spectrometer. H NMR spectra were recorded at 400 or 500 MHz
using TMS as an internal standard and 13C NMR spectra at 75, 100, or
125 MHz using CDCl3 as an internal standard. The following
abbreviations are used to describe peak patterns where appropriate: b,
broad; s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet.
Coupling constants are reported in hertz. HRMS data were obtained
using EI ionization. Melting points were measured with a micro
melting point apparatus.
The propargylic alcohols were prepared according to the published
methods.29 Dichloromethane (DCM) was distilled from CaH2 under a
N2 atmosphere. Molecular sieves (4 Å) were activated by being baked
in a muffle oven. Other materials were purchased from common
commercial sources and used without additional purification.
General Procedure for the Preparation of Dihydroazepines
4−8. To a solution of secondary amine 2 (0.5 mmol) in dry
dichloromethane (3 mL) was added 2-butynedioate 1 (0.5 mmol), and
the solution was stirred for 10 min at room temperature. Then,
propargylic alcohol 3 (0.5 mmol), 4 Å molecular sieves (200 mg), and
BF3·Et2O (0.5 mmol) were added in sequence. After being stirred at
reflux temperature for 1 h, the mixture was evaporated under vacuum.
The product was isolated by silica gel column chromatography with a
hexane/EtOAc/Et3N mixture (10:1:0.1, v/v/v).
Diethyl 1-ethyl-7-methyl-4,6,6-triphenyl-6,7-dihydro-1H-azepine-
2,3-dicarboxylate (4a): yellow solid; 83% yield; mp 158−159 °C; 1H
NMR (400 MHz, CDCl3) δ 7.41 (d, J = 7.9 Hz, 2H), 7.36 (d, J = 8.2
Hz, 2H), 7.32−7.22 (m, 4H), 7.21−7.11 (m, 6H), 7.07 (t, J = 6.8 Hz,
1H), 6.06 (s, 1H), 4.64 (q, J = 6.2 Hz, 1H), 4.11 (q, J = 7.1 Hz, 2H),
3.82−3.54 (m, 2H), 2.96−2.53 (m, 2H), 1.29 (t, J = 6.9 Hz, 3H),
1.24−1.15 (m, 6H), 0.74−0.66 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 169.8, 166.2, 149.0, 147.4, 146.0, 142.2, 140.9, 132.1, 128.3,
127.93, 127.86, 127.8, 127.6, 126.5, 126.2, 125.93, 125.86, 102.9, 62.6,
61.7, 61.6, 60.1, 53.0, 19.2, 16.1, 13.6, 13.3; IR (KBr) ν 2980, 1733,
1691, 1597, 1546, 1444, 1371, 1256, 1089, 704 cm−1; HRMS (EI) m/z
calcd for C33H35NO4 509.2566, found 509.2567.
Diethyl 4-(4-bromophenyl)-1-ethyl-7-methyl-6,6-diphenyl-6,7-di-
hydro-1H-azepine-2,3-dicarboxylate (4b): white solid; 85% yield;
mp 157−158 °C; 1H NMR (400 MHz, CDCl3) δ 7.42−7.33 (m, 4H),
7.30 (t, J = 7.6 Hz, 4H), 7.21−7.14 (m, 3H), 7.13−7.04 (m, 3H), 6.03
(s, 1H), 4.65 (q, J = 6.2 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H), 3.91−3.55
(m, 2H), 3.02−2.55 (m, 2H), 1.29 (t, J = 7.0 Hz, 3H), 1.23−1.13 (m,
6H), 0.78 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.4,
166.0, 148.8, 147.8, 145.0, 142.0, 140.0, 132.4, 130.9, 128.4, 128.2,
127.8, 127.7, 126.03, 125.98, 119.9, 102.2, 62.7, 61.7, 61.6, 60.2, 53.1,
19.2, 16.1, 13.6, 13.5; IR (KBr) ν 1281, 1733, 1690, 1544, 1446, 1367,
1255, 1142, 1091, 701 cm−1; HRMS (EI) m/z calcd for C33H34BrNO4
587.1671, found 587.1678.
Diethyl 1-ethyl-7-methyl-6,6-diphenyl-6,7-dihydro-1H-azepine-
1
2,3-dicarboxylate (4g): white oil; 40% yield; H NMR (400 MHz,
CDCl3) δ 7.42−7.32 (m, 4H), 7.27−7.19 (m, 1H), 7.18−7.02 (m,
4H), 6.89 (d, J = 7.7 Hz, 2H), 6.03 (d, J = 12.2 Hz, 1H), 4.42 (q, J =
6.1 Hz, 1H), 4.29−7.16 (m, 4H), 2.82−2.67 (m, 1H), 2.10−1.89 (m,
1H), 1.36−1.26 (m, 6H), 1.22−1.13 (m, 6H); 13C NMR (100 MHz,
CDCl3) δ 168.1, 166.3, 150.6, 147.6, 145.2, 128.3, 128.1, 127.6, 126.5,
126.3, 126.1, 98.7, 62.0, 61.6, 61.4, 60.4, 51.2, 16.9, 15.1, 14.3, 13.7; IR
(film) ν 2982, 1737, 1689, 1543, 1366, 1255, 1194, 1091, 729, 698
cm−1; HRMS (EI) m/z calcd for C27H31NO4 433.2253, found
433.2250.
Dimethyl 1-ethyl-7-methyl-4-phenyl-6,6-di-p-tolyl-6,7-dihydro-
1H-azepine-2,3-dicarboxylate (4h): white solid; 71% yield; mp
1
161−162 °C; H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 7.3 Hz,
2H), 7.25 (dd, J1 = 12.6 Hz, J2 = 7.6 Hz, 4H), 7.17 (t, J = 7.3 Hz, 1H),
7.09 (d, J = 8.0 Hz, 2H), 7.03−6.93 (m, 4H), 6.06 (s, 1H), 4.58 (q, J =
6.2 Hz, 1H), 3.69 (s, 3H), 3.17 (s, 3H), 2.92−2.53 (m, 2H), 2.28 (s,
3H), 2.23 (s, 3H), 1.27 (t, J = 7.0 Hz, 3H), 1.16 (d, J = 6.4 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 170.4, 166.8, 147.0, 146.2, 146.0,
140.4, 139.7, 135.3, 132.7, 129.0, 128.4, 127.9, 127.7, 127.6, 126.3,
126.1, 103.1, 62.1, 61.1, 53.1, 52.5, 51.2, 20.9, 20.8, 19.0, 15.8; IR (KBr)
ν 2947, 1738, 1699, 1557, 1431, 1262, 1223, 910, 734, 702 cm−1
HRMS (EI) m/z calcd for C33H35NO4 509.2566, found 509.2564.
;
Diethyl 1-ethyl-7-methyl-6,6-diphenyl-4-(p-tolyl)-6,7-dihydro-1H-
azepine-2,3-dicarboxylate (4c): yellow solid; 86% yield; mp 142−
1
143 °C; H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 8.1 Hz, 2H),
Dimethyl 1-ethyl-2-methyl-5-phenyl-1,2-dihydrospiro[azepine-
3,9′-fluorene]-6,7-dicarboxylate (4i): white solid; 53% yield; mp
114−115 °C; 1H NMR (400 MHz, CDCl3) δ 7.73 (dd, J1 = 16.1 Hz, J2
= 7.7 Hz, 2H), 7.43−7.31 (m, 4H), 7.31−7.12 (m, 7H), 5.89 (s, 1H),
3.86 (s, 3H), 3.18 (s, 3H), 3.10−2.99 (m, 2H), 2.37−2.20 (m, 1H),
1.35 (d, J = 6.7 Hz, 3H), 1.00 (t, J = 6.9 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 170.8, 167.1, 150.5, 150.0, 146.4, 145.7, 140.1, 139.9,
139.4, 128.3, 127.8, 127.7, 127.6, 127.0, 126.6, 126.3, 126.1, 125.3,
7.33−7.26 (t, J = 8.1 Hz, 4H), 7.21−4.11 (m, 5H), 7.11−7.03 (m,
3H), 6.04 (s, 1H), 4.63 (q, J = 6.1 Hz, 1H), 4.10 (q, J = 7.1 Hz, 2H),
3.87−3.55 (m, 2H), 3.03−2.50 (m, 2H), 2.31 (s, 3H), 1.29 (t, J = 6.9
Hz, 3H), 1.24−1.12 (m, 6H), 0.73 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 169.9, 166.3, 149.1, 147.2, 143.1, 142.3, 140.7, 135.7,
131.7, 128.5, 128.3, 128.0, 127.8, 127.6, 126.4, 125.9, 125.8, 103.1,
62.6, 61.7, 61.6, 60.1, 53.0, 21.0, 19.2, 16.1, 13.6, 13.4; IR (KBr)
8926
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120.1, 119.6, 106.0, 62.90, 61.92, 52.81, 52.77, 51.5, 17.9, 14.7; IR
(KBr) ν 2945, 1740, 1701, 1548, 1492, 1264, 1221, 1096, 756, 737,
704 cm−1; HRMS (EI) m/z calcd for C31H29NO4 479.2097, found
479.2096.
(m, 2H), 3.72−3.53 (m, 2H), 3.38 (dd, J1 = 17.4 Hz, J2 = 7.6 Hz, 1H),
3.13−3.02 (m, 1H), 2.13−2.03 (m, 2H), 1.64−1.50 (m, 1H), 1.34 (t,
J = 7.1 Hz, 3H), 0.91−0.78 (m, 1H), 0.58 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 168.8, 166.2, 150.7, 146.9, 146.8, 143.4,
138.3, 136.0, 130.2, 128.3, 128.0, 127.8, 127.3, 126.9, 126.7, 126.4,
126.1, 102.3, 71.8, 61.6, 59.6, 51.1, 30.2, 23.1, 13.9, 13.3; IR (KBr) ν
Diethyl 6-(4-chlorophenyl)-1-ethyl-6-(4-methoxyphenyl)-7-meth-
yl-4-phenyl-6,7-dihydro-1H-azepine-2,3-dicarboxylate (4j): yellow
1
2980, 1727, 1694, 1560, 1261, 1222, 1142, 1095, 759, 701 cm−1
HRMS (EI) calcd for C33H33NO4 507.2410, found 507.2412.
;
solid; 60% yield; mp 99−100 °C; H NMR (400 MHz, CDCl3) δ
7.40 (d, J = 7.5 Hz, 2H), 7.31−7.17 (m, 5H), 7.14 (d, J = 8.4 Hz, 2H),
7.08 (d, J = 8.5 Hz, 2H), 6.83 (d, J = 8.5 Hz, 2H), 6.03 (s, 1H), 4.58
(q, J = 6.0 Hz, 1H), 4.19−4.02 (m, 2H), 3.80−3.55 (m, 5H), 3.07−
2.58 (m, 2H), 1.35−1.27 (t, J = 6.9 Hz, 3H), 1.23−1.13 (m, 6H), 0.69
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.6, 166.0,
157.5, 147.5, 145.6, 141.1, 131.8, 131.5, 129.4, 128.6, 127.8, 127.6,
126.5, 126.3, 113.8, 102.7, 63.0, 61.7, 60.4, 60.2, 55.2, 53.3, 19.3, 16.2,
13.5, 13.4; IR (KBr) ν 2981, 1738, 1698, 1552, 1510, 1255, 1093,
1037, 832, 701 cm−1; HRMS (EI) m/z calcd for C34H36ClNO5
573.2282, found 573.2285.
Dimethyl 7,9,9-triphenyl-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]-
azepine-5,6-dicarboxylate (4p): white solid; 65% yield; mp 187−
1
188 °C; H NMR (400 MHz, CDCl3) δ 7.36−7.29 (m, 4H), 7.29−
7.12 (m, 11H), 6.10 (s, 1H), 4.52 (t, J = 6.6 Hz, 1H), 3.86 (s, 3H),
3.36 (dd, J = 16.5, 8.1 Hz, 1H), 3.14−3.02 (m, 4H), 2.16−1.98 (m,
2H), 1.67−1.53 (m, 1H), 0.95−0.80 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 169.3, 166.6, 150.7, 146.8, 146.6, 143.3, 138.4, 135.8, 130.1,
128.3, 128.0, 127.8, 127.3, 126.7, 126.54, 126.48, 126.1, 101.9, 71.8,
59.4, 52.6, 51.2, 50.8, 30.2, 23.0; IR (KBr) ν 2948, 1735, 1701, 1560,
1442, 1271, 1225, 1143, 760, 702 cm−1; HRMS (EI) m/z calcd for
C31H29NO4 479.2097, found 479.2098.
Diethyl 1-ethyl-6,7-dimethyl-4,6-diphenyl-6,7-dihydro-1H-aze-
pine-2,3-dicarboxylate (4k): white oil; 54% yield; 1H NMR (400
MHz, CDCl3) δ 7.46 (d, J = 8.1 Hz, 1H), 7.39−7.14 (m, 9H), 6.14 (s,
0.5H), 5.57 (s, 0.5H), 4.37−4.22 (m, 1H), 4.16−4.01 (m, 1H), 3.76−
3.41 (m, 4H), 3.00−2.66 (m, 0.5H), 2.54−2.38 (m, 0.5H), 1.55 (s,
1.5H), 1.44 (s, 1.5H), 1.41−1.31 (m, 3H), 1.24−1.16 (m, 1.5H),
1.16−1.07 (m, 3H), 0.90 (d, J = 6.6 Hz, 1.5H), 0.72−0.58 (m, 3H);
13C NMR (100 MHz, CDCl3) δ 170.2, 170.0, 166.7, 166.4, 147.6,
146.8, 146.7, 146.6, 146.4, 143.0, 139.9, 137.5, 132.9, 131.7, 128.2,
127.9, 127.8, 126.72, 126.67, 126.5, 126.2, 126.0, 125.9, 103.2, 102.3,
66.4, 65.5, 61.9, 61.5, 60.2, 60.1, 52.6, 52.1, 51.3, 48.9, 30.0, 24.0, 17.4,
17.2, 15.8, 15.4, 13.7, 13.6, 13.3, 13.2; IR (film) ν 2979, 1737, 1698,
1549, 1444, 1258, 1217, 1097, 761, 701 cm−1; HRMS (EI) m/z calcd
for C28H33NO4 447.2410, found 447.2406.
Diethyl 8,10,10-triphenyl-1,2,3,4,10,10a-hexahydropyrido[1,2-a]-
azepine-6,7-dicarboxylate (4q): white solid; 73% yield; mp 191−192
1
°C; H NMR (400 MHz, CDCl3) δ 7.52−7.40 (m, 6H), 7.36−7.20
(m, 5H), 7.20−7.09 (m, 3H), 7.05 (t, J = 7.0 Hz, 1H), 6.72 (s, 1H),
4.73 (d, J = 8.7 Hz, 1H), 4.32−4.06 (m, 2H), 3.71−3.52 (m, 3H), 3.13
(t, J = 11.8 Hz, 1H), 1.86 (s, 1H), 1.79−1.55 (m, 5H), 1.27 (t, J = 7.0
Hz, 3H), 0.64 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
166.7, 166.6, 149.9, 146.2, 144.6, 144.2, 141.1, 133.4, 128.6, 127.9,
127.7, 126.8, 126.6, 126.2, 125.9, 125.8, 100.3, 72.5, 61.4, 58.9, 54.5,
54.0, 31.4, 27.4, 25.2, 13.9, 13.6; IR (KBr) ν 2935, 1729, 1691, 1547,
1492, 1445, 1256, 1117, 1040, 746, 702 cm−1; HRMS (EI) m/z calcd
for C34H35NO4 521.2566, found 521.2568.
Dimethyl 1-ethyl-4,6,6,7-tetraphenyl-6,7-dihydro-1H-azepine-
Dimethyl 7-ethyl-4,6,6-triphenyl-1-propyl-6,7-dihydro-1H-aze-
1
2,3-dicarboxylate (4s): white solid; 59% yield; mp 175−176 °C; H
pine-2,3-dicarboxylate (4l): white solid; 77% yield; mp 208−209
1
NMR (400 MHz, CDCl3) δ 7.51 (d, J = 7.8 Hz, 2H), 7.37 (d, J = 7.6
Hz, 2H), 7.33−7.16 (m, 6H), 7.15−7.05 (m, 4H), 7.04−6.93 (m, 4H),
6.81 (d, J = 7.6 Hz, 2H), 6.52 (s, 1H), 5.61 (s, 1H), 3.78 (s, 3H),
3.42−3.11 (m, 2H), 3.05 (s, 3H), 1.11 (t, J = 7.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 168.3, 166.9, 150.6, 145.1, 144.5, 144.2, 141.1,
140.2, 133.3, 129.9, 128.8, 128.1, 128.0, 127.8, 127.6, 127.3, 127.1,
126.5, 126.34, 126.29, 126.0, 100.9, 57.0, 52.5, 50.6, 50.4, 14.4; IR
°C; H NMR (400 MHz, CDCl3) δ 7.38−7.23 (m, 8H), 7.22−7.14
(m, 4H), 7.13−7.07 (m, 1H), 7.07−7.01 (m, 2H), 6.11 (s, 1H), 4.28
(d, J = 9.3 Hz, 1H), 3.70 (d, J = 2.0 Hz, 3H), 3.19 (d, J = 2.1 Hz, 3H),
2.53−2.20 (m, 2H), 1.65−1.24 (m, 4H), 1.16 (t, J = 7.2 Hz, 3H), 0.62
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 166.9,
149.6, 146.5, 146.1, 142.7, 140.0, 133.8, 128.5, 128.3, 128.1, 127.9,
127.7, 126.5, 126.2, 126.0, 106.3, 69.9, 63.3, 60.0, 52.6, 51.5, 24.0, 23.0,
12.2, 11.1; IR (KBr) ν 2969, 1741, 1708, 1553, 1492, 1429, 1260,
1217, 1094, 753, 701 cm−1; HRMS (EI) m/z calcd for C33H35NO4
509.2566, found 509.2569.
(KBr) ν 2947, 1738, 1698, 1557, 1266, 1445, 1126, 910, 725, 699 cm−1
HRMS (EI) m/z calcd for C36H33NO4 543.2410, found 543.2411.
;
Diethyl 1-ethyl-4,6,6,7-tetraphenyl-6,7-dihydro-1H-azepine-2,3-
dicarboxylate (4t): white solid; 52% yield; mp 165−166 °C; 1H
NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.5
Hz, 2H), 7.33−7.16 (m, 6H), 7.15−7.06 (m, 4H), 7.05−6.95 (m, 4H),
6.83 (d, J = 7.4 Hz, 2H), 6.48 (s, 1H), 5.62 (s, 1H), 4.22 (q, J = 7.0
Hz, 2H), 3.54 (q, J = 7.1 Hz, 2H), 3.44−3.10 (m, 2H), 1.27 (t, J = 7.1
Hz, 3H), 1.10 (t, J = 7.1 Hz, 3H), 0.57 (t, J = 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.6, 166.4, 150.7, 145.1, 144.8, 144.3, 141.3,
140.5, 133.0, 129.9, 128.8, 128.2, 127.9, 127.8, 127.5, 127.3, 127.1, 126.4,
126.3, 126.1, 101.0, 77.7, 61.5, 59.2, 57.0, 50.3, 14.5, 13.8, 13.4; IR (KBr)
ν 2977, 1734, 1690, 1554, 1493, 1441, 1257, 1220, 1132, 700 cm−1;
HRMS (EI) m/z calcd for C38H37NO4 571.2723, found 571.2716.
Diethyl 8,10,10-triphenyl-3,4,10,10a-tetrahydro-1H-[1,4]oxazino-
[4,3-a]azepine-6,7-dicarboxylate (4r): white solid; 34% yield; mp
Dimethyl 1-butyl-4,6,6-triphenyl-7-propyl-6,7-dihydro-1H-aze-
pine-2,3-dicarboxylate (4m): white solid; 81% yield; mp 184−185
1
°C; H NMR (400 MHz, CDCl3) δ 7.39−7.22 (m, 8H), 7.18 (t, J =
7.2 Hz, 4H), 7.12−7.01 (m, 3H), 6.11 (s, 1H), 4.36 (d, J = 9.5 Hz,
1H), 3.68 (s, 3H), 3.19 (s, 3H), 2.54−2.27 (m, 2H), 1.87−1.69 (m,
1H), 1.59−1.31 (m, 4H), 1.29−1.13 (m, 1H), 1.05−0.85 (m, 5H),
0.78 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 166.8,
149.6, 146.6, 146.2, 142.7, 140.0, 133.8, 128.5, 128.3, 128.1, 127.9,
127.7, 126.4, 126.2, 126.1, 126.0, 106.3, 68.5, 63.3, 58.1, 52.5, 51.4,
33.5, 31.6, 20.8, 19.9, 14.5, 13.6; IR (KBr) ν 2960, 1738, 1696, 1547,
1444, 1253, 1202, 1093, 758, 702 cm−1; HRMS (EI) m/z calcd for
C35H39NO4 537.2879, found 537.2876.
Dimethyl 1-benzyl-4,6,6,7-tetraphenyl-6,7-dihydro-1H-azepine-
2,3-dicarboxylate (4n): white solid; 78% yield; mp 153−154 °C;
1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.6 Hz, 2H), 7.40−7.12
1
172−173 °C; H NMR (400 MHz, CDCl3) δ 7.51−7.39 (m, 6H),
7.36−7.25 (m, 4H), 7.22−711 (m, 3H), 7.07 (t, J = 7.3 Hz, 1H), 6.86
(s, 1H), 4.96 (d, J = 9.0 Hz, 1H), 4.32−4.16 (m, 2H), 3.84 (dd, J1 =
34.0 Hz, J2 = 11.1 Hz, 2H), 3.69−3.48 (m, 4H), 3.47−3.32 (m, 2H),
1.30 (t, J = 7.1 Hz, 3H), 0.65 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 166.2, 166.0, 150.2, 144.6, 144.4, 143.3, 141.9, 133.4,
128.8, 128.0, 127.9, 126.7, 126.4, 126.2, 126.0, 103.6, 73.2, 71.3, 67.4,
61.7, 59.1, 52.2, 13.9, 13.5; IR (KBr) ν 2977, 1735, 1695, 1560, 1365,
1261, 1122, 1075, 748, 702 cm−1; HRMS (EI) m/z calcd for
C33H33NO5 523.2359, found 523.2351.
(m, 13H), 7.11−6.93 (m, 6H), 6.80 (t, J = 4.0 Hz, 2H), 6.75 (d, J = 7.6
Hz, 2H), 6.51 (s, 1H), 5.47 (s, 1H), 4.35 (d, J = 15.3 Hz, 1H), 4.10 (d,
J = 15.3 Hz, 1H), 3.82 (s, 3H), 3.10 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 168.0, 167.6, 151.0, 144.8, 144.3, 143.8, 140.1, 139.8, 134.1,
130.4, 128.6, 128.5, 128.3, 128.2, 128.1, 127.7, 127.4, 127.3, 127.1,
126.6, 126.3, 126.2, 126.0, 101.4, 74.6, 56.2, 55.9, 52.7, 50.7; IR (KBr) ν
2980, 1727, 1694, 1553, 1492, 1444, 1356, 1261, 1142, 759, 701 cm−1
;
HRMS (EI) m/z calcd for C41H35NO4 605.2566, found 605.2563.
Dimethyl 1-methyl-4,6,6,7-tetraphenyl-6,7-dihydro-1H-azepine-
2,3-dicarboxylate (4u): white solid; 32% yield; mp 194−195 °C;
1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.7 Hz, 2H), 7.39 (d, J =
Diethyl 7,9,9-triphenyl-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]-
azepine-5,6-dicarboxylate (4o): white solid; 64% yield; mp
1
141−142 °C; H NMR (400 MHz, CDCl3) δ 7.36−7.28 (m, 4H),
7.28−7.12 (m, 11H), 6.06 (s, 1H), 4.52 (t, J = 6.7 Hz, 1H), 4.37−4.23
7.5 Hz, 2H), 7.30 (t, J = 7.2 Hz, 4H), 7.25−7.17 (m, 2H), 7.14−7.05
8927
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Article
(m, 4H), 7.01 (t, J = 7.5 Hz, 2H), 7.05−6.97 (m, 2H), 6.75 (d, J = 7.5
Hz, 2H), 6.56 (s, 1H), 5.41 (s, 1H), 3.82 (s, 3H), 3.05 (s, 3H), 2.93 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 168.0, 166.8, 151.1, 144.7,
144.6, 144.5, 140.2, 140.0, 133.0, 129.8, 128.8, 128.0, 127.9, 127.72,
127.69, 127.5, 127.2, 126.5, 126.41, 126.37, 126.0, 100.2, 81.2, 56.5,
52.5, 50.6, 41.3; IR (KBr) ν 2947, 1741, 1698, 1558, 1494, 1448, 1270,
1131, 755, 699 cm−1; HRMS (EI) m/z calcd for C35H31NO4 529.2253,
found 529.2250.
Dimethyl 2-benzyl-5-(diphenylmethylene)-1-methyl-4-phenyl-
2,5-dihydro-1H-pyrrole-2,3-dicarboxylate (6a): yellow solid; 45%
1
yield; mp 119−120 °C; H NMR (400 MHz, CDCl3) δ 7.43−7.31
(m, 3H), 7.22−7.07 (m, 5H), 6.91−6.59 (m, 10H), 6.36 (s, 1H), 6.28
(d, J = 6.0 Hz, 1H), 3.87 (s, 3H), 3.62−3.42 (m, 5H), 2.42 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 171.1, 163.8, 153.6, 150.5, 143.4,
141.9, 136.3, 134.2, 132.4, 131.6, 130.8, 130.3, 128.8, 128.4, 127.9,
127.5, 126.8, 126.6, 126.5, 125.5, 125.4, 115.1, 79.0, 52.8, 51.4, 37.9,
34.3; IR (KBr) ν 2951, 1730, 1617, 1439, 1366, 1238, 1172, 1106, 758,
697 cm−1; HRMS (EI) m/z calcd for C35H31NO4 529.2253, found
529.2249.
Diethyl 1-methyl-4,6,6,7-tetraphenyl-6,7-dihydro-1H-azepine-
2,3-dicarboxylate (4v): white solid; 20% yield; mp 170−171 °C;
1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 7.7 Hz, 2H), 7.40 (d, J =
Diethyl 2-benzyl-5-(diphenylmethylene)-1-methyl-4-phenyl-2,5-
dihydro-1H-pyrrole-2,3-dicarboxylate (6b): yellow solid; 56% yield;
mp 114−115 °C; 1H NMR (400 MHz, CDCl3) δ 7.41−7.31 (m, 3H),
7.22−7.06 (m, 5H), 6.88−6.59 (m, 10H), 6.36 (s, 1H), 6.28 (d, J = 7.3
Hz, 1H), 4.41−4.25 (m, 2H), 4.02 (q, J = 6.9 Hz, 2H), 3.59 (d, J =
14.4 Hz, 1H), 3.47 (d, J = 14.5 Hz, 1H), 2.43 (s, 3H), 1.37 (t, J = 7.0
Hz, 3H), 0.96 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
170.4, 163.4, 153.2, 150.9, 143.5, 142.0, 136.5, 134.4, 132.9, 132.3,
131.7, 130.8, 130.3, 128.8, 128.5, 127.9, 127.5, 126.8, 126.5, 125.43,
125.37, 114.6, 79.0, 61.6, 60.2, 37.7, 34.3, 14.4, 13.7; IR (KBr) ν 2983,
1728, 1700, 1617, 1378, 1214, 1175, 1035, 758, 698 cm−1; HRMS (EI)
m/z calcd for C37H35NO4 557.2566, found 557.2574.
Dimethyl 4-(2,2-diphenylvinyl)-1-isopropyl-4,5-diphenyl-4,5-di-
hydro-1H-pyrrole-2,3-dicarboxylate (7a): white solid; 49% yield;
mp 174−175 °C; 1H NMR (400 MHz, CDCl3) δ 7.47 (t, J = 7.5 Hz,
2H), 7.38 (d, J = 7.8 Hz, 2H), 7.34−7.18 (m, 7H), 7.09−6.95 (m,
5H), 6.89 (s, 2H), 6.76 (s, 2H), 6.20 (s, 1H), 5.49 (s, 1H), 3.99 (s,
3H), 3.53 (s, 3H), 3.01−2.86 (m, 1H), 0.79 (d, J = 7.0 Hz, 3H), 0.59
(d, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.3, 164.9,
153.5, 145.1, 143.2, 142.9, 140.6, 137.0, 136.3, 131.3, 128.8, 128.3,
128.0, 127.9, 127.5, 127.43, 127.38, 127.2, 127.1, 127.0, 125.9, 108.3,
75.0, 58.2, 52.8, 50.9, 48.8, 20.5, 20.2; IR (KBr) ν 2948, 1750, 1685,
1576, 1491, 1222, 1135, 789, 723, 703 cm−1; HRMS (EI) m/z calcd
for C37H35NO4 557.2566, found 557.2565.
7.3 Hz, 2H), 7.34−7.16 (m, 6H), 7.15−7.07 (m, 4H), 7.02 (t, J = 7.5
Hz, 2H), 6.98−6.90 (m, 2H), 6.77 (d, J = 7.5 Hz, 2H), 6.54 (s, 1H),
5.42 (s, 1H), 4.26 (q, J = 7.1 Hz, 2H), 3.65−3.41 (m, 2H), 2.95 (s,
3H), 1.31 (t, J = 7.1 Hz, 3H), 0.55 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 167.2, 166.3, 151.2, 144.8, 144.7, 144.6, 140.5, 140.1,
132.6, 129.8, 127.93, 127.87, 127.7, 127.6, 127.4, 127.2, 126.4, 126.34,
126.28, 126.2, 100.1, 81.3, 61.5, 59.0, 56.4, 41.1, 13.8, 13.4; IR (KBr) ν
2927, 1734, 1695, 1629, 1560, 1266, 1134, 1078, 721, 699 cm−1
;
HRMS (EI) m/z calcd for C37H35NO4 557.2566, found 557.2569.
Dimethyl 1-isopropyl-4,6,6,7-tetraphenyl-6,7-dihydro-1H-aze-
pine-2,3-dicarboxylate (4w): white solid; 23% yield; mp 173−174
°C; 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 7.8 Hz, 2H), 7.37 (d,
J = 7.6 Hz, 2H), 7.33−7.01 (m, 12H), 6.95 (t, J = 7.3 Hz, 2H), 6.82 (d,
J = 7.8 Hz, 2H), 6.49 (s, 1H), 5.78 (s, 1H), 3.93−3.82 (m, 1H), 3.78
(s, 3H), 3.06 (s, 3H), 1.46 (d, J = 6.4 Hz, 3H), 0.73 (d, J = 6.7 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 168.4, 167.5, 150.7, 145.4,
144.4, 144.1, 142.3, 140.1, 133.7, 130.5, 128.7, 128.1, 128.0, 127.8,
127.5, 127.1, 126.7, 126.4, 126.2, 125.9, 71.7, 57.1, 56.7, 52.4, 50.6,
24.7, 19.9; IR (KBr) ν 2947, 1738, 1669, 1538, 1494, 1431, 1262,
1105, 910, 735, 699 cm−1; HRMS (EI) m/z calcd for C37H35NO4
557.2566, found 557.2569.
Diethyl 1-isopropyl-4,6,6,7-tetraphenyl-6,7-dihydro-1H-azepine-
2,3-dicarboxylate (4x): white solid; 16% yield; mp 167−168 °C;
1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 7.4 Hz, 2H), 7.41 (d, J =
Diethyl 4-(2,2-diphenylvinyl)-1-isopropyl-4,5-diphenyl-4,5-dihy-
dro-1H-pyrrole-2,3-dicarboxylate (7b): white solid; 52% yield; mp
131−132 °C; 1H NMR (400 MHz, CDCl3) δ 7.46 (t, J = 7.5 Hz, 2H),
7.40 (d, J = 7.3 Hz, 2H), 7.33−7.16 (m, 7H), 7.09−6.96 (m, 5H), 6.91
(s, 2H), 6.76 (s, 2H), 6.23 (s, 1H), 5.46 (s, 1H), 4.45 (q, J = 7.1 Hz,
2H), 4.17−3.89 (m, 2H), 3.04−2.89 (m, 1H), 1.48 (t, J = 7.1 Hz, 3H),
0.99 (t, J = 7.1 Hz, 3H), 0.79 (d, J = 7.0 Hz, 3H), 0.59 (d, J = 6.7 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 164.6, 164.4, 153.5, 145.3,
143.1, 142.8, 140.6, 137.3, 136.8, 131.3, 128.7, 128.3, 128.0, 127.5,
127.3, 127.2, 127.0, 126.9, 125.8, 108.6, 74.7, 61.9, 59.0, 58.4, 48.9,
20.5, 20.3, 14.3, 14.0; IR (KBr) ν 2980, 1745, 1685, 1588, 1443, 1367,
1219, 1184, 1132, 702 cm−1; HRMS (EI) m/z calcd for C39H39NO4
585.2879, found 585.2880.
7.1 Hz, 2H), 7.35−7.18 (m, 5H), 7.18−7.01 (m, 7H), 6.95 (t, J = 7.3
Hz, 2H), 6.83 (d, J = 7.3 Hz, 2H), 6.46 (s, 1H), 5.79 (s, 1H), 4.33−
4.21 (m, 2H), 4.09−3.82 (m, 1H), 3.54 (q, J = 6.2 Hz, 2H), 1.46 (d,
J = 6.3 Hz, 3H), 1.25 (t, J = 7.0 Hz, 3H), 0.76 (d, J = 6.5 Hz, 3H), 0.59
(t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.6, 166.9,
151.0, 145.4, 144.7, 144.3, 142.6, 140.5, 133.2, 130.5, 128.8, 128.2,
127.9, 127.8, 127.4, 127.1, 126.7, 126.4, 126.2, 126.1, 101.7, 71.7, 61.4,
59.1, 57.0, 56.2, 24.9, 19.9, 13.7, 13.4; IR (KBr) ν 2981, 1734, 1695,
1546, 1493, 1248, 1222, 1101, 1030, 699 cm−1; HRMS (EI) m/z calcd
for C39H39NO4 585.2879, found 585.2877.
Dimethyl 1-isobutyl-7-isopropyl-4,6,6-triphenyl-6,7-dihydro-1H-
azepine-2,3-dicarboxylate (4y): white solid; 17% yield; mp 137−
138 °C; 1H NMR (500 MHz, CDCl3) δ 7.51 (d, J = 7.7 Hz, 2H), 7.43
(d, J = 7.3 Hz, 2H), 7.37−7.26 (m, 6H), 7.21 (t, J = 7.3 Hz, 1H), 7.13
(dd, J1 = 14.9 Hz, J2 = 7.5 Hz, 3H), 7.02 (t, J = 7.3 Hz, 1H), 6.56 (s,
1H), 4.78 (d, J = 3.4 Hz, 1H), 3.66 (s, 3H), 3.15 (s, 3H), 2.98−2.85 (m,
2H), 2.23−2.09 (m, 1H), 1.72−1.62 (m, 1H), 1.08 (d, J = 7.0 Hz, 3H),
0.98 (d, J = 6.8 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H), 0.58 (d, J = 6.6 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 169.8, 166.8, 149.7, 148.8, 145.0,
142.0, 140.8, 131.8, 128.29, 128.28, 128.0, 127.6, 126.4, 125.8, 103.3,
72.3, 64.2, 59.9, 52.3, 51.1, 35.4, 26.2, 25.6, 21.3, 20.9, 19.6; IR (KBr) ν
2960, 1741, 1709, 1547, 1256, 1214, 1109, 1088, 750, 702 cm−1; HRMS
(EI) m/z calcd for C35H39NO4 537.2879, found 537.2891.
Dimethyl 2-(isobutylamino)-3-[(E)-1,3,3-triphenylprop-1-en-1-yl]-
1
maleate (8): white solid; 58% yield; mp 94−95 °C; H NMR (400
MHz, CDCl3) δ 7.31 (s, 5H), 7.10−6.91 (m, 10H), 4.56 (s, 1H), 3.81
(s, 3H), 3.34 (s, 3H), 2.58−2.35 (m, 2H), 2.14 (s, 1H), 1.82−1.68 (m,
1H), 0.93 (t, J = 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 172.2,
169.1, 149.5, 146.3, 142.2, 140.4, 139.3, 131.6, 130.2, 128.5, 128.2, 128.1,
127.5, 127.4, 127.2, 126.6, 62.2, 55.7, 52.4, 51.3, 28.6, 20.5; IR (KBr) ν
3384, 2958, 1735, 1686, 1581, 1492, 1431, 1252, 757, 700 cm−1; HRMS
(EI) m/z calcd for C31H33NO4 483.2410, found 483.2408.
Procedure for the Preparation of 9. To a solution of diethyl-
amine (2a) (1 mmol) in dry dichloromethane (3 mL) was added
methyl propiolate (1 mmol), and the solution was stirred at room
temperature for 10 min. Then, propargylic alcohol (3a) (1 mmol), 4 Å
molecular sieves (400 mg), and BF3·Et2O (1 mmol) were added in
sequence. The mixture was stirred for 1 h and then evaporated under
vacuum. The residue was purified by silica gel column chromatography
with a hexane/EtOAc mixture (10:1, v/v) to afford pure 9 (191 mg,
52% yield).
(Z)-Methyl 2-formyl-3,5,5-triphenylpenta-2,4-dienoate (9): yel-
low solid; 52% yield; mp 127−128 °C; 1H NMR (400 MHz,
CDCl3) δ 9.30 (s, 1H), 7.40−7.26 (m, 5H), 7.17−6.96 (m, 9H), 6.87
(d, J = 7.3 Hz, 2H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3)
Diethyl 4-(diphenylmethylene)-1-morpholino-3-phenylcyclobut-
2-ene-1,2-dicarboxylate (5): yellow solid; 31% yield; mp 98−99 °C;
1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 3.6 Hz, 2H), 7.34−7.26
(m, 3H), 7.09 (t, J = 6.9 Hz, 3H), 6.99 (t, J = 6.8 Hz, 3H), 6.95−6.82
(m, 4H), 4.27−4.01 (m, 4H), 3.68 (d, J = 3.6 Hz, 4H), 2.85 (s, 4H),
1.22 (t, J = 7.1 Hz, 3H), 1.09 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 169.8, 162.4, 161.5, 139.1, 138.7, 136.9, 136.2, 130.9,
130.5, 130.2, 128.4, 128.3, 128.0, 127.6, 127.4, 127.3, 126.9, 78.0, 67.5,
60.9, 60.4, 48.8, 14.03, 13.95; IR (KBr) ν 2925, 1743, 1704, 1444,
1330, 1243, 1177, 1117, 762, 698 cm−1; HRMS (EI) m/z calcd for
C33H33NO5 523.2359, found 523.2366.
8928
dx.doi.org/10.1021/jo2016407|J. Org. Chem. 2011, 76, 8922−8929

The Journal of Organic Chemistry
Article
δ 189.8, 167.0, 159.2, 154.2, 141.6, 139.0, 135.3, 134.3, 130.7, 130.4,
129.2, 128.5, 128.3, 128.0, 127.7, 127.4, 126.4, 52.5; IR (KBr) ν 2855,
1729, 1651, 1568, 1329, 1310, 1269, 1147, 775, 702 cm−1; HRMS (EI)
m/z calcd for C25H20O3 368.1412, found 368.1405.
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ASSOCIATED CONTENT
■
S
* Supporting Information
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3963. (b) Bernard, J.; Schnieders, C.; Mullen, K. J. Chem. Soc., Chem.
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Copies of 1H and 13C NMR spectra and crystallographic
information (CIF files) for compounds 4a, 6b, 7a, and 8. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: pinglu@zju.edu.cn; orgwyg@zju.edu.cn.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(Grants 21032005 and 20872128) for financial support.
(15) Yao, L.-F.; Shi, M. Org. Lett. 2007, 9, 5187.
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(18) CCDC 827903 contains the supplementary crystallographic
data for 4a. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.
uk/data_request/cif.
(19) The diethyl 2-(diethylamino)maleate is pure according to the
1H NMR spectrum: 1H NMR (400 MHz, CDCl3) δ 4.60 (s, 1H), 4.41
(q, J = 7.2 Hz, 2H), 4.09 (q, J = 7.1 Hz, 2H), 3.19 (q, J = 7.1 Hz, 4H),
1.38 (t, J = 7.2 Hz, 3H), 1.27−1.15 (m, 9H).
(20) Yao, L.-F.; Shi, M. Chem.Eur. J. 2009, 15, 3875.
(21) CCDC 827904 contains the supplementary crystallographic
data for 6b.
(22) CCDC 833052 contains the supplementary crystallographic
data for 7a.
(23) CCDC 833053 contains the supplementary crystallographic
data for 8.
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