Copper-Catalyzed Difunctionalization of Terminal Alkynes with Diazo Esters and Amines to Construct β-Enamino Esters

Article abstract of DOI:10.1002/adsc.201600883

An operationally simple and efficient copper-catalyzed three-component tandem reaction of terminal alkynes, diazo compounds and amines to yield β-enamino esters is described. This straightforward protocol takes place rapidly with a wide range of substrates and gives the desired β-enamino esters in good to excellent yields. Preliminary mechanistic studies suggested that the reaction probably proceeds through Cu-catalyzed formal C–H insertion to produce an alkynoate intermediate, which was then trapped by amines to give the β-enamino esters. (Figure presented.).

Full text of DOI:10.1002/adsc.201600883

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DOI: 10.1002/adsc.201600883
Copper-Catalyzed Difunctionalization of Terminal Alkynes with
Diazo Esters and Amines to Construct b-Enamino Esters
Bao Gaoa and Hanmin Huanga,*
a
Department of Chemistry, University of Science and Technology of China, Hefei 230026, Peopleꢀs Republic of China
Fax : (+86)-551-6360-1592; e-mail: hanmin@ustc.edu.cn
Received: August 10, 2016; Revised: October 8, 2016; Published online: && &&, 0000
Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201600883.
Abstract: An operationally simple and efficient studies suggested that the reaction probably pro-
copper-catalyzed three-component tandem reaction ceeds through Cu-catalyzed formal C–H insertion to
of terminal alkynes, diazo compounds and amines to produce an alkynoate intermediate, which was then
yield b-enamino esters is described. This straightfor- trapped by amines to give the b-enamino esters.
ward protocol takes place rapidly with a wide range
of substrates and gives the desired b-enamino esters Keywords: copper; diazo esters; b-enamino esters;
in good to excellent yields. Preliminary mechanistic tandem reaction; terminal alkynes
Introduction
the synthesis of nitrogen-containing molecules. In this
context, 3-alkynoates and 2,3-allenoates, produced by
b-Enamino esters have long been recognized as im- copper-catalyzed coupling of terminal alkynes with a-
portant precursors for the synthesis of chiral b-amino diazo esters via C–H insertion,[7] could be viewed as
acids and a variety of versatile biologically active mol- important precursors for synthesis of b-enamino
ecules.[1,2] As a result, there has been a long-standing esters since the N–H addition reaction could be easily
interest in the efficient synthesis of such molecules, realized with amines under suitable reaction condi-
and a number of methods have been devised for their tions.[8] Inspired by these facts, we envisioned that
preparation.[3] However, most of these reported meth- a cascade reaction involving C–H insertion and N–H
ods relied on multiple-step reactions and suffered addition with terminal alkynes, diazo compounds and
from limited substrate scope as well as harsh reaction amines could be realized. However, identification of
conditions. For these reasons, it is highly interesting suitable reaction conditions and catalyst to suppress
to develop alternative synthetic methodologies that the N–H insertion between diazo esters and amines is
can selectively access such scaffolds from simple start- a significant challenge.
ing materials under mild reaction conditions. In this
context, we turned to develop a new catalytic system
toward these compounds by combining C–C and C–N
bond-forming reactions. Herein, we describe
a copper-catalyzed three-component reaction of ter-
minal alkynes, diazo compounds and amines to yield
b-enamino esters (Scheme 1).[4]
The transition metal-catalyzed insertion of metal
carbenes or carbenoids into C–H bonds represents
one of the most efficient strategies to construct C–C
bonds and has received considerable development.[5]
On the other hand, the catalytic N–H addition to C–
C multiple bond is one of most highly desirable and
atom-economic C–N bond formation reactions for the
synthesis of organonitrogen molecules.[6] Judiciously
combining the above C–C and C–N bond-forming re-
actions would establish some efficient protocols for esters.
Scheme 1. New strategy for the synthesis of b-enamino
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Results and Discussion
that the highest yield (96%) was obtained when the
ratio of 1a/2a was set at 1/1.5, and 4a was obtained in
On the basis of the above working hypothesis, we 96% isolated yield (Table 1, entry 12). Further optimi-
chose phenylacetylene (1a), ethyl diazoacetate (2a) zation of the reaction conditions, such as reaction
and dibenzylamine (3a) as model substrates to investi- temperature, time and solvents gave no improvement
gate the reaction conditions. Initially, the commonly in the yield of the reaction.
used rhodium salts for the normal C–H or N–H inser-
The scope and limitations of the optimized reaction
tion reactions, such as Rh2(OAc)4, [Cp*RhCl2]2 and conditions were investigated and a series of alkynes
[Rh(COD)Cl2]2 were screened in toluene as catalyst with diazo compounds and amines were found to be
for the target cascade reaction. None yielded the de- amenable to the reaction. As shown in Table 2, all ar-
sired product. After several trials, we turned our at- omatic alkynes underwent the cascade reaction in
tention to using copper as a catalyst. The desired high yields and selectivities regardless of the nature
product 4a could be obtained when the reaction was and the position of the substituents. Generally, a sub-
conducted in the presence of a catalytic amount of stituent at the para-position slightly enhanced the
copper salts (Table 1, entry 4–8). Screening of some yield, while one at the ortho-position diminished the
representative copper salts revealed that the most ef- reactivity. It was noteworthy that the strong electron-
ficient catalysis was furnished with CuI with which withdrawing NO2 could also be compatible with the
the desired product 4a was afforded in 80% isolated current reaction to provide the product in 90% yield.
yield. The solid state structure of 4a was unambigu- In addition to phenylacetylene and its derivatives,
ously determined by single-crystal X-ray crystallo- naphthyl-substituted alkynes, such as 1-ethynylnaph-
graphic analysis (see the Supporting Information).[9] thalene and 2-ethynylnaphthalene, could be also con-
Notably, only the E-isomer was observed in all cases, verted into the corresponding products in good to ex-
which indicated that the second step of the N–H addi- cellent yields. Furthermore, the methodology was
tion reaction was performed in a cis-manner. Subse- equally effective for a heteroaryl-substituted alkyne
quent investigation of the ratio of 1a/2a demonstrated to give the corresponding product 4k in 98% yield.
Table 1. Screening of the reaction conditions.[a]
Entry
[M]
Solvent
2a [equiv.]
Temperature [oC]
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
Rh2(OAc)4
[Cp*RhCl2]2
[Rh(COD)Cl2]2
CuI
CuBr
CuBr2
CuCl
CuCl2
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
CH3CN
THF
1,4-dioxane
anisole
MeOH
toluene
toluene
toluene
toluene
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.2
1.3
1.4
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
10
8
0
0
0
80
67
73
23
16
90
92
95
96
88
94
69
90
80
23
92
88
91
90
9
10
11
12
13
14
15
16
17
18
19
20
21
22
60
100
100
CuI
[a]
Reaction conditions: 1a (0.5 mmol), 3a (0.75 mmol), [Cu] (5 mol%) or [Rh] (2 mol%), solvent (2 mL), 1008C, 12 h.
Isolated yields.
[b]
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Table 2. Substrate scope of alkynes and amines.[a]
Entry
R1
R2
R3
Product
Yield [%][b]
1
2
3
4
5
6
7
8
Ph
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Et
n-Pr
i-Pr
allyl
n-Bu
n-Oct
4-ClBn
4-MeBn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Et
n-Pr
i-Pr
allyl
n-Bu
n-Oct
4-ClBn
4-MeBn
n-Pr
4-BrBn
4a
4b
4c
4d
4e
4f
4g
4h
4i
96
92
95
89
82
86
82
90
92
85
98
62
56
93
89
94
91
93
85
93
99
91
95
4-MeC6H4
4-MeOC6H4
3-MeOC6H4
2-MeC6H4
3,4,5-(Me)3C6H2
4-FC6H4
4-NO2C6H4
1-naphthyl
2-naphthyl
2-thienyl
TMS
n-Bu
Ph
Ph
Ph
Ph
Ph
Ph
Ph
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4j
4k
4l
4m
5a
5b
5c
5d
5e
5f
5g
5h
5i
Ph
Ph
Ph
Bn
5j
24
Ph
Ph
5k
5l
55
75
25
Bn
H
[a]
Reaction conditions: 1 (0.5 mmol), 2a (0.75 mmol), 3 (0.75 mmol), CuI (5 mol%), toluene (2 mL), 1008C, 12 h.
Isolated yields.
[b]
Interestingly, aliphatic alkynes, such as trimethylsilyl- be attributed to steric hindrance. Furthermore, a pri-
acetylene and 1-hexyne were compatible with the re- mary amine (BnNH2) was also applicable, giving the
action conditions to afford products 4l and 4m in rela- desired product 5l in 75% yield, which would provide
tively lower yields,[10] suggesting that aliphatic alkynes a platform for the further transformations of b-enami-
are less reactive in this cascade reaction.
no esters. Unfortunately, when aromatic amines were
We also surveyed the scope of this new cascade re- utilized as nucleophiles, only trace amounts of the de-
action with respect to the amines. As depicted in sired products were detected. Alternatively, the corre-
Table 2, a variety of aliphatic amines was successfully sponding N–H insertion products and alkynoates
transformed to the corresponding products in good to were observed as by-products, which might be as-
excellent yields. In general, symmetrical secondary cribed to the weaker nucleophilicity of aromatic
amines were all compatible with the reaction to give amines.
the desired products in good to excellent yields re-
Subsequently, the reactions of phenylacetylene 1a
gardless of the carbon chain length (85–94%, 5a-5-f). and dibenzylamine 3a with various substituted a-
Moreover, the para-substituted dibenzylamines 3g diazo esters were also performed under the slightly
and 3h were amenable to this catalytic system to give modified reaction conditions. As shown in Table 3, all
the desired products in excellent yields (5g and 5h) of the reactions underwent smoothly with a series of
and no obvious electronic effect was observed. Un- aromatic a-diazo esters to give the desired tetra-sub-
symmetrical secondary amines could also be convert- stituted b-enamino esters in good to excellent yields.
ed into b-enamino esters in excellent yields (5i and Typical functional groups contained in the aromatic
5j). However, the cyclic morpholine gave the desired ring, such as Me (2b, 2c), OMe (2d, 2e), F (2f, 2g),
product 5k in relatively lower yield (55%), which may and Cl (2h–2j) were well tolerated with CH2Cl2 as sol-
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Table 3. Substrate scope of dizao compounds.[a]
was hydrolyzed in the presence of HCl (6M) to
afford intermediate 8. The intermediate 8 could be
easily converted into b-lactam 9 with 2-chloro-1-meth-
ylpyridinium iodide as a condensing reagent under
mild reaction conditions, which is a common building
block existing in many antibiotics.[11]
To gain some preliminary understanding of the
mechanism, several experiments were performed
(Scheme 3). Firstly, ethyl 4-phenylbut-3-ynoate 10 and
ethyl 4-phenylbuta-2,3-dienoate 11 were prepared and
reacted with Bn2NH in the absence of CuI, respec-
tively. As expected, these two compounds could be
converted into the desired product 4a in excellent
yields. To further identify whether the product is ob-
tained from 10 or 11, an in-situ NMR experiment was
conducted under the standard reaction conditions
(see the Supporting Information). The results demon-
strated that alkynoate 10 was quickly formed and no
2,3-allenoate 11 was observed. As time went on,
Entry
Ar
Product
Yield [%]
Z/E
1
2
3
4
5
6
7
8
C6H5
6a
6b
6c
6d
6e
6f
6g
6h
6i
91
89
90
86
88
92
92
97
98
97
95
46/54
46/54
35/65
44/56
48/52
43/57
44/56
4-MeC6H4
3,5-Me2C6H3
4-MeOC6H4
3-MeOC6H4
4-FC6H4
3-FC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
2-naphthyl
42/58 alkynACTHNGUTERNNUoG ate 10 was gradually consumed and the product
9
10
11
41/59
43/57
36/64
produced, implying that the alkynoate is the real in-
termediate for this transformation.
6j
6k
[a]
Reaction conditions: 1a (0.5 mmol), 2 (0.75 mmol), 3a
(0.75 mmol), CuI (5 mol%), CH2Cl2 (2 mL), 1008C, 12 h.
Isolated yields.
[b]
vent. The substrates examined here with electron-
withdrawing groups gave over 90% yields. In addition
to substituted phenyl diazoacetates, the naphthyl-sub-
stituted diazo compound 2k was also subjected to this
reaction, generating the b-enamino ester 6k in 95%
isolated yield. However, the Z/E ratio of the desired
products was almost 1:1, which indicated that the N–
H addition reaction was not regioselective. The solid
Scheme 3. Mechanistic studies.
On the basis of previous reports[12] and the above
state structure of E-6a was unambiguously deter- preliminary mechanistic studies, a mechanism was
mined by single-crystal X-ray crystallographic analysis postulated to account for this transformation
(see the Supporting Information).[9]
(Figure 1). The catalytic cycle is likely initiated by the
We further evaluated the utility of this reaction reaction of low-valent CuI with phenylacetylene to
(Scheme 2). The double bond of 5l could be selective-
ly reduced by NaBH(OAc)3 to give product 7, which
Scheme 2. Synthetic utility of the b-enamino esters.
Figure 1. Plausible reaction mechanism.
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with ethyl acetate/petroleum ether (1/50–1/20) to afford the
desired products.
give copper acetylide A, which reacted with ethyl di-
azoacetate to form metal carbenoid B. Subsequent
migratory insertion and protonation released low-
valent Cu(I) to sustain the next catalytic cycle and at
the same time intermediate alkynoate 10 was ob-
tained. In the presence of dibenzylamine, hydroami-
nation of alkynoate 10 afforded the desired product
4a.
(E)-Ethyl 3-(dibenzylamino)-4-phenylbut-2-enoate (4a):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give
a
white solid; yield: 185.7 mg (96%); 1H NMR
(400 MHz, CDCl3): d=7.29–7.33 (m, 6H), 7.20–7.27 (m,
5H), 7.06 (d, J=7.2 Hz, 4H), 5.07 (s, 1H), 4.53 (s, 2H), 4.44
(s, 4H), 4.04 (q, J=7.2 Hz, 2H), 1.21 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=168.9, 161.6, 137.6, 136.9,
128.8, 128.8, 128.0, 127.4, 126.4, 126.3, 87.5, 58.7, 52.9, 33.9,
14.6; HR-MS (ESI): m/z=408.1934, calcd. for C26H27NO2Na
[M+Na]: 408.1934.
Conclusions
(E)-Ethyl 3-(dibenzylamino)-4-p-tolylbut-2-enoate (4b):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give the colorless oil; yield: 183.7 mg (92%); 1H NMR
(400 MHz, CDCl3): d=7.27–7.33 (m, 4H), 7.22–7.25 (m,
2H), 7.11–7.15 (m, 4H), 7.07 (d, J=7.2 Hz, 4H), 5.05 (s,
1H), 4.44–4.47 (m, 6H), 4.03 (q, J=7.2 Hz, 2H), 2.33 (s,
3H), 1.21 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=169.0, 161.9, 137.0, 135.9, 134.5, 129.5, 128.9, 127.9, 127.4,
126.5, 87.4, 58.7, 53.0, 33.6, 21.2, 14.7; HR-MS (ESI): m/z=
422.2084, calcd. for C27H29NO2Na [M+Na]: 422.2091.
(E)-Ethyl 3-(dibenzylamino)-4-(4-methoxyphenyl)but-2-
enoate (4c): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give the colorless oil; yield: 196.8 mg (95%);
1H NMR (400 MHz, CDCl3): d=7.30–7.34 (m, 4H), 7.26 (t,
J=6.4 Hz, 2H), 7.16 (d, J=8.8 Hz, 2H), 7.07 (d, J=6.8 Hz,
4H),.6.85 (d, J=8.8 Hz, 2H), 5.03 (s, 1H), 4.45 (s, 6H), 4.04
(q, J=7.2 Hz, 2H), 3.80 (s, 3H), 1.21 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=169.0, 162.1, 158.3, 137.1,
129.7, 129.1, 128.9, 127.4, 126.5, 114.3, 87.3, 58.8, 55.4, 53.0,
33.2, 14.7; HR-MS (ESI): m/z=438.2049, calcd. for C27H29
NO3Na [M+Na]: 438.2040.
(E)-Ethyl 3-(dibenzylamino)-4-(3-methoxyphenyl)but-2-
enoate (4d): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give a white solid; yield: 185.1 mg (89%);
1H NMR (400 MHz, CDCl3): d=7.28–7.34 (m, 4H), 7.21–
7.27 (m, 3H), 7.09 (d, J=7.2 Hz, 4H), 6.76–6.85 (m, 3H),
5.06 (s, 1H), 4.51 (s, 2H), 4.45 (s, 4H), 4.04 (q, J=7.2 Hz,
2H), 3.77 (s, 3H), 1.21 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=169.0, 161.5, 160.2, 139.3, 137.0,
129.8, 128.9, 127.5, 126.5, 120.6, 113.5, 112.1, 87.6, 58.8, 55.3,
53.1, 34.0, 14.7; HR-MS (ESI): m/z=438.2039, calcd. for
C27H29NO3Na [M+Na]: 438.2040.
In summary, we have developed a Cu-catalyzed three-
component reaction that combines diazoacetates, al-
kynes and amines for the facile construction of b-en-
amino esters. The reactions proceed by trapping a re-
active alkynoate intermediate, generated by the Cu-
catalyzed coupling reaction of diazoacetate and
alkyne, with amines. A broad range of substrates was
compatible with the reaction conditions to afford b-
enamino esters, particularly for tetra-substituted b-en-
amino esters in good to excellent yields. Preliminary
mechanistic studies conducted by in situ NMR con-
firmed that the reactive alkynoate was involved as
a key intermediate.
Experimental Section
General Experimental Details and Materials
All non-aqueous reactions and manipulations were per-
formed by using standard Schlenk techniques. All solvents
before use were dried and degassed by standard methods
and stored under argon atmosphere. All reactions were
monitored by TLC with silica gel-coated plates. NMR spec-
tra were recorded on Bruker Avance III (400 MHz) spec-
trometers. Chemical shifts are reported in parts per million
(ppm) downfield from TMS with the solvent resonance as
the internal standard. Coupling constants (J) are reported in
Hz and refer to apparent peak multiplicities. High resolution
mass spectra (HR-MS) were recorded on a Bruker Micro-
TOF-QII mass instrument (ESI). Alkynes 1a, 1b, 1g, 1l, 1m
were purchased from Energy Chemical. All of the other ter-
minal alkynes 1c–1f and 1h–1k were synthesized using
known methods.[13] Ethyl a-diazoacetate was purchased
from Aldrich and the other a-diazo esters used here are
known compounds and were synthesized according to the
reported methods.[14]
(E)-Ethyl 3-(dibenzylamino)-4-(2-methoxyphenyl)but-2-
enoate (4e): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give a white solid; yield: 170.5 mg (82%);
1H NMR (400 MHz, CDCl3): d=7.17–7.33 (m, 8H), 7.06 (d,
J=7.2 Hz, 4H), 6.93–6.97 (m, 1H), 6.80 (d, J=8.0 Hz, 1H),
5.07 (s, 1H), 4.51 (s, 2H), 4.40 (s, 4H), 4.03 (q, J=7.2 Hz,
2H), 3.73 (s, 3H), 1.20 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=169.0, 162.6, 156.8, 137.2, 128.8,
128.4, 127.4, 127.3, 126.7, 125.9, 120.9, 110.4, 87.6, 58.7, 55.4,
52.7, 27.1, 14.7; HR-MS (ESI): m/z=438.2034, calcd. for
C27H29NO3Na [M+Na]: 438.2040.
General Procedure for the Synthesis of Product b-
Enamino Esters
A mixture of alkyne 1 (0.5 mmol), diazo compound 2
(0.75 mmol), amine 3 (0.75 mmol), CuI (4.8 mg, 0.025 mmol)
and toluene (2.0 mL) was added to a 25-mL flame-dried
Young-type tube. The mixture was degassed via the freeze-
thaw method and then stirred at 1008C for 12 hours. After
cooling to room temperature, the reaction mixture was puri-
fied by neutral alumina column chromatography and eluted
(E)-Ethyl 3-(dibenzylamino)-4-(3,4,5-trimethoxyphenyl)-
but-2-enoate (4f): The title compound was prepared accord-
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ing to the general procedure and purified by flash column
chromatography to give a white solid; yield: 205.3 mg
(86%); H NMR (400 MHz, CDCl3): d=7.26–7.36 (m, 6H),
7.12 (d, J=6.8 Hz, 4H), 6.46 (s, 2H), 5.07 (s, 1H), 4.48 (s,
6H), 4.05 (q, J=7.2 Hz, 2H), 3.83 (s, 3H), 3.79 (s, 6H), 1.22
(t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=168.9,
161.2, 153.6, 137.1, 136.5, 133.3, 129.0, 127.5, 126.4, 104.8,
87.4, 61.0, 58.8, 56.1, 53.1, 34.1, 14.7; HR-MS (ESI): m/z=
498.2250, calcd. for C29H33NO5Na [M+Na]: 498.2251.
7.28 (m, 2H), 7.16–7.18 (m, 1H), 7.09 (d, J=7.2 Hz, 4H),
6.93–6.95 (m, 1H), 6.88–6.90 (m, 1H), 4.97 (s, 1H), 4.66 (s,
2H), 4.50 (s, 4H), 4.05 (q, J=7.2 Hz, 2H), 1.21(t, J=6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=168.8, 161.5, 140.6,
136.8, 129.0, 127.5, 126.9, 126.5, 125.0, 124.0, 86.9, 58.9, 53.0,
29.0, 14.7; HR-MS (ESI): m/z=414.1491, calcd. for
C24H25NO2SNa [M+Na]: 414.1498.
1
(E)-Ethyl 3-(dibenzylamino)but-2-enoate (4l): The title
compound was prepared according to the general procedure
and purified by flash column chromatography to give
a white solid; yield: 130.2 mg (84%); 1H NMR (400 MHz,
CDCl3): d=7.32–7.36 (m, 4H), 7.25–7.29 (m, 2H), 7.13 (d,
J=7.2 Hz, 4H), 4.86 (s, 1H), 4.51 (s, 4H), 4.04 (q, J=
7.2 Hz, 2H), 2.61 (s, 3H), 1.22 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=169.5, 161.3, 136.9, 129.0, 127.5,
126.5, 85.9, 58.6, 52.9, 15.5, 14.7; HR-MS (ESI): m/z=
332.1605, calcd. for C20H23NO2Na [M+Na]: 332.1621.
(E)-Ethyl 3-(dibenzylamino)oct-2-enoate (4m): The title
compound was prepared according to the general procedure
and purified by flash column chromatography to give the
colorless oil; yield: 102.5 mg (56%); 1H NMR (400 MHz,
CDCl3): d=7.32–7.36 (m, 4H), 7.25–7.29 (m, 2H), 7.11(d,
J=7.2 Hz, 4H), 4.78 (s, 1H), 4.47 (s, 4H), 4.03 (q, J=
7.2 Hz, 2H), 3.02 (br, 2H), 1.63–1.70 (m, 2H), 1.32–1.45 (m,
4H), 1.21 (t, J=6.8 Hz, 3H), 0.89 (t, J=6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=168.8, 165.8, 137.0, 128.9,
127.4, 126.6, 85.0, 58.5, 52.4, 32.3, 29.5, 28.7, 22.6, 14.8, 14.2;
HR-MS (ESI): m/z=366.2423, calcd. for C24H32NO2 [M+H]:
366.2428.
(E)-Ethyl
3-(dibenzylamino)-4-(4-fluorophenyl)but-2-
enoate (4g): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give a white solid; yield: 165.1 mg (82%);
1H NMR (400 MHz, CDCl3): d=7.24–7.34 (m, 6H), 7.19–
7.22 (m, 2H), 7.05 (d, J=7.2 Hz, 4H), 7.00 (t, J=8.8 Hz,
2H), 5.05 (s, 1H), 4.44–4.47 (m, 6H), 4.04 (q, J=6.8 Hz,
2H), 1.22 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=168.9, 162.9, 161.4, 160.4, 136.9, 133.3, 129.6, 129.5, 128.9,
127.5, 126.4, 115.7, 115.5, 87.7, 58.8, 53.0, 33.2, 14.6;
19F NMR (376 MHz, CDCl3): d=À116.93; HR-MS (ESI):
m/z=426.1828, calcd. for C26H26FNO2Na [M+Na]:
426.1840.
(E)-Ethyl
3-(dibenzylamino)-4-(4-nitrophenyl)but-2-
enoate (4h): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give the yellow oil; yield: 194.4 mg (90%);
1H NMR (400 MHz, CDCl3): d=8.17 (d, J=8.8 Hz, 2H),
7.26–7.41 (m, 8H), 7.07 (d, J=6.8 Hz, 4H), 5.13 (s, 1H),
4.62 (s, 2H), 4.44 (s, 4H), 4.04 (q, J=6.8 Hz, 2H), 1.23 (t,
J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=168.9,
159.9, 146.8, 145.8, 136.6, 129.1, 128.9, 127.8, 126.4, 124.1,
88.5, 59.1, 53.3, 34.1, 14.7; HR-MS (ESI): m/z=431.1967,
calcd. for C26H27N2O4 [M+H]: 431.1965.
(E)-Ethyl 3-(diethylamino)-4-phenylbut-2-enoate (5a):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give
a
white solid; yield: 121.7 mg (93%); 1H NMR
(E)-Ethyl
3-(dibenzylamino)-4-(naphthalen-1-yl)but-2-
(400 MHz, CDCl3): d=7.24–7.28 (m, 2H), 7.14–7.19 (m,
3H), 4.82 (s, 1H), 4.45 (s, 2H), 4.04 (q, J=7.2 Hz, 2H),
3.17–3.23 (m, 4H), 1.24 (t, J=7.2 Hz, 3H), 1.04–1.09 (m,
6H); 13C NMR (100 MHz, CDCl3): d=169.2, 160.3, 138.2,
128.7, 127.8, 126.1, 84.6, 58.5, 43.9, 33.5, 14.8, 12.8; HR-MS
(ESI): m/z=284.1628, calcd for C16H23NO2Na [M+Na]:
284.1621.
(E)-Ethyl 3-(dipropylamino)-4-phenylbut-2-enoate (5b):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give the colorless oil; yield: 128.6 mg (89%); 1H NMR
(400 MHz, CDCl3): d=7.24–7.28 (m, 2H), 7.14–7.18 (m,
3H), 4.79 (s, 1H), 4.45 (s, 2H), 4.05 (q, J=7.2 Hz, 2H), 3.07
(t, J=8.0 Hz, 4H), 1.49–1.54 (m, 4H), 1.24 (t, J=7.2 Hz,
3H), 0.82 (t, J=7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3):
d=169.1, 160.7, 138.2, 128.6, 127.8, 126.0, 84.9, 58.4, 51.8,
33.6, 20.7, 14.8, 11.3; HR-MS (ESI): m/z=312.1926, calcd.
for C18H27NO2Na [M+Na]: 312.1934.
enoate (4i): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give a white solid; yield: 200.1 mg (92%);
1H NMR (400 MHz, CDCl3): d=7.82–7.89 (m, 2H), 7.72–
7.75 (m, 1H), 7.40–7.46 (m, 4H), 7.19–7.35 (m, 6H), 7.12 (d,
J=7.2 Hz, 4H), 5.23 (s, 1H), 4.91 (s, 2H), 4.41 (s, 4H), 3.99
(q, J=7.2 Hz, 2H), 1.17 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=168.8, 161.8, 137.1, 134.0, 133.5,
131.8, 128.9, 128.9, 127.5, 127.1, 126.6, 126.2, 125.8, 125.7,
124.0, 123.0, 88.0, 58.7, 53.3, 30.7, 14.7; HR-MS (ESI): m/z=
458.2094, calcd. for C30H29NO2Na [M+Na]: 458.2091.
(E)-Ethyl
3-(dibenzylamino)-4-(naphthalen-1-yl)but-2-
enoate (4j): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give the pale yellow oil; yield: 185.2 mg (85%);
1H NMR (400 MHz, CDCl3): d=7.80–7.83 (m, 2H), 7.75–
7.77 (m, 1H), 7.67 (s, 1H), 7.38–7.49 (m, 3H), 7.23–7.35 (m,
6H), 7.10 (d, J=7.2 Hz, 4H), 5.13 (s, 1H), 4.69 (s, 2H), 4.46
(s, 4H), 4.05 (q, J=7.2 Hz, 2H), 1.22 (t, J=6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=169.0, 161.4, 137.1, 135.4,
133.9, 132.4, 129.0, 127.8, 127.7, 127.5, 126.9, 126.5, 126.2,
126.1, 125.5, 87.7, 58.9, 53.2, 34.1, 14.7; HR-MS (ESI): m/z=
458.2079, calcd. for C30H29NO2Na [M+Na]: 458.2091.
(E)-Ethyl
3-(diisopropylamino)-4-phenylbut-2-enoate
(5c): The title compound was prepared according to the gen-
eral procedure and purified by flash column chromatogra-
1
phy to give a white solid; yield: 135.6 mg (94%); H NMR
(400 MHz, CDCl3): d=7.24–7.28 (m, 2H), 7.13–7.19 (m,
3H), 4.98 (s, 1H), 4.51 (s, 2H), 4.04 (q, J=7.2 Hz, 2H),
3.81–3.87 (m, 2H), 1.16–1.25 (m, 15H); 13C NMR (100 MHz,
CDCl3): d=169.0, 159.0, 138.7, 128.6, 127.8, 125.9, 87.9, 76.8,
58.4, 47.7, 34.6, 20.4, 14.9; HR-MS (ESI): m/z=290.2100,
calcd. for C18H28NO2 [M+H]: 290.2115.
(E)-Ethyl
3-(dibenzylamino)-4-(thiophen-2-yl)but-2-
enoate (4k): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give a white solid; yield: 192.2 mg (98%);
1H NMR (400 MHz, CDCl3): d=7.31–7.34 (m, 4H), 7.23–
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(E)-Ethyl 3-(diallylamino)-4-phenylbut-2-enoate (5d): The
title compound was prepared according to the general pro-
cedure and purified by flash column chromatography to give
the pale yellow oil; yield: 129.2 mg (91%); 1H NMR
(400 MHz, CDCl3): d=7.26–7.30 (m, 2H), 7.16–7.21 (m,
3H), 5.62–5.72 (m, 2H), 5.06–5.17 (m, 4H), 4.92 (s, 1H),
4.45 (s, 2H), 4.05 (q, J=7.2 Hz, 2H), 3.76 (d, J=4.8 Hz,
4H), 1.24 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d=169.0, 161.2, 137.9, 132.6, 128.8, 127.9, 126.2, 116.8, 86.4,
58.7, 51.8, 33.7, 14.8; HR-MS (ESI): m/z=286.1789, calcd.
for C18H24NO2 [M+H]: 286.1802.
2H), 4.37 (s, 2H), 4.05 (q, J=7.2 Hz, 2H), 3.17 (t, J=
8.0 Hz, 2H), 1.54–1.63 (m, 2H), 1.24 (t, J=7.2 Hz, 3H), 0.83
(t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=169.1,
161.2, 137.9, 137.7, 128.9, 128.8, 127.9, 127.3, 126.3, 126.3,
86.2, 58.7, 53.2, 52.2, 33.8, 14.8, 11.4; HR-MS (ESI): m/z=
360.1921, calcd. for C22H27NO2Na [M+Na]: 360.1934.
(E)-Ethyl 3-[benzyl(4-bromobenzyl)amino]-4-phenylbut-
2-enoate (5j): The title compound was prepared according
to the general procedure and purified by flash column chro-
matography to give the pale yellow oil; yield: 220.8 mg
1
(95%); H NMR (400 MHz, CDCl3): d=7.41 (d, J=8.4 Hz,
(E)-Ethyl 3-(dibutylamino)-4-phenylbut-2-enoate (5e):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give the pale yellow oil; yield: 146.9 mg (93%); 1H NMR
(400 MHz, CDCl3): d=7.25–7.28 (m, 2H), 7.15–7.18 (m,
3H), 4.79 (s, 1H), 4.45 (s, 2H), 4.05 (q, J=7.2 Hz, 2H), 3.10
(t, J=7.6 Hz, 4H), 1.45–1.47 (m, 4H), 1.19–1.28 (m, 7H),
0.89 (t, J=7.2 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=
169.2, 160.7, 138.2, 128.6, 127.8, 126.1, 84.8, 58.5, 50.0, 33.6,
20.3, 14.8, 14.0; HR-MS (ESI): m/z=318.2418, calcd. for
C20H32NO2 [M+H]: 318.2428.
(E)-Ethyl 3-(dioctylamino)-4-phenylbut-2-enoate (5f):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give the pale yellow oil; yield: 181.5 mg (85%); 1H NMR
(400 MHz, CDCl3): d=7.24–7.28 (m, 2H), 7.14–7.18 (m,
3H), 4.78 (s, 1H), 4.44 (s, 2H), 4.05 (q, J=7.2 Hz, 2H), 3.09
(t, J=7.6 Hz, 4H), 1.47 (br, 4H), 1.19–1.32 (m, 23H), 0.88
(t, J=6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3): d=169.2,
160.7, 138.2, 128.6, 127.8, 126.0, 84.8, 58.4, 50.2, 33.6, 31.9,
29.4, 29.3, 27.1, 22.7, 14.8, 14.2; HR-MS (ESI): m/z=
452.3491, calcd. for C28H47NO2Na [M+Na]: 452.3499.
2H), 7.22–7.33 (m, 8H), 7.04 (d, J=7.2 Hz, 2H), 6.91 (d, J=
8.4 Hz, 2H), 5.02 (s, 1H), 4.51 (s, 2H), 4.41(s, 2H), 4.36 (s,
2H), 4.04 (q, J=6.8 Hz, 2H), 1.21 (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3): d=168.9, 161.4, 137.5, 136.8,
136.0, 132.0, 129.0, 128.9, 128.2, 128.1, 127.6, 126.5, 126.5,
121.2, 88.1, 58.9, 53.0, 52.5, 34.0, 14.7; HR-MS (ESI): m/z=
486.1027, calcd. for C26H26BrNO2Na [M+Na]: 486.1039.
(E)-Ethyl 4-phenyl-3-(piperidin-1-yl)but-2-enoate (5k):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give the colorless oil; yield: 75.1 mg (55%); 1H NMR
(400 MHz, CDCl3): d=7.26–7.30 (m, 2H), 7.16–7.20 (m,
3H), 4.99 (s, 1H), 4.46 (s, 2H), 4.07 (q, J=7.2 Hz, 2H), 3.55
(t, J=4.8 Hz, 4H), 3.20 (t, J=4.8 Hz, 4H), 1.25 (t, J=
6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=168.8, 161.9,
137.9, 128.7, 127.9, 126.3, 89.4, 66.4, 59.0, 46.8, 33.5, 14.7;
HR-MS (ESI): m/z=298.1417, calcd. for C16H21NO3Na [M+
Na]: 298.1414.
(E)-Ethyl 3-(benzylamino)-4-phenylbut-2-enoate (5l): The
title compound was prepared according to the general pro-
cedure and purified by flash column chromatography to give
the pale yellow oil; yield: 110.3 mg (75%); 1H NMR
(400 MHz, CDCl3): d=8.97 (s, 1H), 7.27–7.31 (m, 4H),
7.21–7.24 (m, 4H), 7.15–7.17 (m, 2H), 4.55 (s, 1H), 4.26 (d,
J=6.0 Hz, 2H), 4.08 (q, J=6.8 Hz, 2H), 3.50 (s, 2H), 1.25
(t, J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=170.8,
163.0, 138.8, 136.5, 128.9, 128.7, 127.5, 127.0, 126.9, 85.0,
58.7, 46.8, 39.1, 14.7; HR-MS (ESI): m/z=318.1455, calcd.
for C19H21NO2Na [M+Na]: 318.1465.
Ethyl 3-(dibenzylamino)-2,4-diphenylbut-2-enoate (6a):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give a white solid; yield: 209.3 mg (91%); Z/E=46/54 (de-
termined by 1H NMR); 1H NMR (400 MHz, CDCl3): d=
7.58 (d, J=7.6 Hz, 1.05H), 7.39 (t, J=7.2 Hz, 1.12H), 7.18–
7.30 (m, 13.15H), 7.09–7.10 (m, 1.72H), 6.86–6.91 (m,
3.27H), 4.38 (s, 1.05H), 4.20 (s, 1.90H), 4.12–4.18 (m,
1.92H), 3.74 (s, 2.08H), 3.63 (s, 0.90H), 1.12–1.17 (m, 3H);
13C NMR (100 MHz, CDCl3): d=171.1, 168.7, 159.4, 157.9,
140.8, 140.1, 139.3, 138.8, 137.9, 137.5, 131.1, 130.8, 129.4,
128.9, 128.7, 128.6, 128.6, 128.4, 128.2, 128.1, 128.0, 127.5,
127.4, 126.5, 126.3, 125.9, 111.7, 108.7, 60.2, 59.9, 55.5, 54.2,
38.6, 38.2, 14.6, 14.4; HR-MS (ESI): m/z=484.2259, calcd.
for C32H31NO2Na [M+Na]: 484.2247.
(E)-Ethyl
3-[bis(4-chlorophenyl)amino]-4-phenylbut-2-
enoate (5g): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give a pale yellow solid; yield: 210.5 mg (93%);
1H NMR (400 MHz, CDCl3): d=7.28–7.34 (m, 4H), 7.21–
7.27 (m, 5H), 6.95 (d, J=8.4 Hz, 4H), 5.0 (s, 1H), 4.50 (s,
2H), 4.37 (s, 4H), 4.05 (q, J=7.2 Hz, 2H), 1.22 (t, J=
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=168.8, 161.1,
137.4, 135.3, 133.3, 129.1, 129.0, 128.1, 127.9, 126.6, 88.6,
59.0, 52.4, 33.9, 14.7; HR-MS (ESI): m/z=476.1142, calcd.
for C26H25Cl2NO2Na [M+Na]: 476.1155.
(E)-Ethyl 3-(di-p-tolylamino)-4-phenylbut-2-enoate (5h):
The title compound was prepared according to the general
procedure and purified by flash column chromatography to
give the colorless oil; yield: 204.6 mg (99%); 1H NMR
(400 MHz, CDCl3): d=7.29–7.33 (m, 2H), 7.19–7.25 (m,
3H), 7.11 (d, J=8.0 Hz, 4H), 6.95 (d, J=7.6 Hz, 4H), 5.06
(s, 1H), 4.52 (s, 2H), 4.38 (s, 4H), 4.03 (q, J=7.2 Hz, 2H),
2.33 (s, 6H), 1.21 (t, J=6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d=169.1, 161.7, 137.8, 137.1, 133.9, 129.6, 128.8,
128.1, 126.4, 126.4, 87.2, 58.7, 52.6, 34.0, 21.2, 14.7; HR-MS
(ESI): m/z=436.2244, calcd. for C28H31NO2Na [M+Na]:
436.2247.
Ethyl
3-(dibenzylamino)-4-phenyl-2-p-tolylbut-2-enoate
(E)-Ethyl 4-phenyl-3-[propyl(p-tolyl)amino]but-2-enoate
(5i): The title compound was prepared according to the gen-
eral procedure and purified by flash column chromatogra-
phy to give the pale yellow oil; yield: 153.7 mg (91%);
1H NMR (400 MHz, CDCl3): d=7.27–7.34 (m, 5H), 7.18–
7.25 (m, 3H), 7.05 (d, J=7.2 Hz, 2H), 4.94 (s, 1H), 4.47 (s,
(6b): The title compound was prepared according to the
general procedure and purified by flash column chromatog-
raphy to give a white solid; yield: 210.2 mg (89%); Z/E=46/
54 (determined by H NMR); H NMR (400 MHz, CDCl3):
d=7.57 (d, J=7.2 Hz, 1.05H), 7.37 (t, J=8.0 Hz, 1.15H),
7.15–7.29 (m, 12.09H), 7.03 (d, J=8.0 Hz, 0.99H), 6.90–6.92
1
1
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(m, 3.10H), 6.75 (d, J=8.0 Hz, 1.03H), 4.35 (s, 1.07H),
4.11–4.20 (m, 3.96H), 3.75 (s, 2.03H), 3.63 (s, 0.91H), 2.28
(s, 1.33H), 2.26 (s, 1.63H), 1.12–1.18 (m, 3H); 13C NMR
(100 MHz, CDCl3): d=171.3, 168.8, 158.8, 157.6, 139.4,
138.9, 138.0, 137.8, 137.7, 137.0, 135.8, 135.4, 130.8, 130.6,
129.4, 128.9, 128.7, 128.6, 128.5, 128.5, 128.2, 127.4, 127.3,
126.5, 111.6, 108.6, 60.1, 59.8, 55.5, 54.1, 38.6, 38.2, 21.3, 21.2,
14.6, 14.4; HR-MS (ESI): m/z=476.2565, calcd. for
C33H34NO2 [M+H]: 476.2583.
to the general procedure and purified by flash column chro-
matography to give a white solid; yield: 220.3 mg (92%);
1
1
Z/E=43/57 (determined by H NMR); H NMR (400 MHz,
CDCl3): d=7.57 (d, J=7.2 Hz, 1.13H), 7.39 (t, J=7.6 Hz,
1.18H), 7.16–7.32 (m, 11.71H), 6.88–6.94 (m, 3.12H), 6.76
(d, J=7.2 Hz, 2.23H), 4.40 (s, 1.12H), 4.22 (m, 1.70H),
4.11–4.19 (m, 2.05H), 3.74 (s, 2.28H), 3.61 (s, 0.86H), 1.12–
1.17 (m, 3H); 13C NMR (100 MHz, CDCl3): d=170.9, 168.4,
162.9, 162.4, 160.0, 158.4, 139.2, 138.6, 137.8, 137.3, 136.8,
136.8, 136.1, 136.1, 132.7, 132.6, 132.4, 132.3, 129.4, 128.7,
128.7, 128.6, 128.3, 128.2, 127.6, 127.5, 126.6, 115.1, 114.9,
114.9, 114.7, 110.7, 107.3, 60.3, 59.9, 55.7, 54.2, 38.7, 38.1,
14.6, 14.4; 19F NMR (376 MHz, CDCl3): d=À116.65,
À116.75; HR-MS (ESI): m/z=480.2335, calcd. for
C32H31FNO2 [M+H]: 480.2333.
Ethyl 3-(dibenzylamino)-2-(3,5-dimethylphenyl)-4-phenyl-
but-2-enoate (6c): The title compound was prepared accord-
ing to the general procedure and purified by flash column
chromatography to give a white solid; yield: 219.9 mg
(90%); Z/E=35/65 (determined by 1H NMR); 1H NMR
(400 MHz, CDCl3): d=7.59 (d, J=7.6 Hz, 1.27H), 7.39 (t,
J=7.6 Hz, 1.30H), 7.18–7.30 (m, 10.03H), 6.88–6.92 (m,
3.30H), 6.81 (s, 0.35H), 6.70 (s, 0.67H), 6.51 (s, 1.27H), 4.35
(s, 1.31H), 4.14–4.21 (m, 3.36H), 3.73 (s, 2.60H), 3.62 (s,
0.70H), 2.23 (s, 2.08H), 2.09 (s, 3.96H), 1.15–1.19 (m, 3H);
13C NMR (100 MHz, CDCl3): d=171.5, 169.0, 158.2, 157.5,
140.4, 139.6, 139.4, 139.1, 138.0, 137.6, 137.3, 137.1, 129.5,
128.9, 128.8, 128.6, 128.5, 128.5, 128.4, 128.2, 128.1, 127.7,
127.5, 127.3, 126.5, 126.4, 112.0, 109.0, 60.2, 59.9, 55.4, 53.9,
38.6, 38.3, 21.4, 21.3, 14.6, 14.4; HR-MS (ESI): m/z=
512.2563, calcd. for C34H35NO2Na [M+Na]: 512.2560.
Ethyl 3-(dibenzylamino)-2-(4-methoxyphenyl)-4-phenyl-
but-2-enoate (6d): The title compound was prepared accord-
ing to the general procedure and purified by flash column
chromatography to give a white solid; yield: 212.1 mg
(86%); Z/E=44/56 (determined by 1H NMR); 1H NMR
(400 MHz, CDCl3): d=7.57 (d, J=7.2 Hz, 1.14H), 7.38 (t,
J=7.6 Hz, 1.19H), 7.16–7.32 (m, 11.95H), 6.89–6.92 (m,
2.28H), 6.76–6.79 (m, 2.01H), 6.62–6.65 (m, 1.11H), 4.35 (s,
1.11H), 4.11–4.19 (m, 3.84H), 3.76 (s, 5.28H), 3.63 (s,
0.88H), 1.13–1.88 (m, 3H); 13C NMR (100 MHz, CDCl3):
d=171.3, 168.9, 158.8, 158.2, 157.7, 157.7, 139.4, 139.0, 138.0,
137.7, 133.2, 132.5, 132.1, 131.9, 129.5, 128.9, 128.7, 128.6,
128.5, 128.2, 127.5, 127.4, 126.5, 113.6, 113.4, 111.4, 108.2,
60.2, 59.9, 55.5, 55.3, 54.1, 38.6, 38.2, 14.7, 14.4; HR-MS
(ESI): m/z=514.2366, calcd. for C33H33NO3Na [M+Na]:
514.2353.
Ethyl 3-(dibenzylamino)-2-(3-methoxyphenyl)-4-phenyl-
but-2-enoate (6e): The title compound was prepared accord-
ing to the general procedure and purified by flash column
chromatography to give a white solid; yield: 217.2 mg
(88%); Z/E=48/52 (determined by 1H NMR); 1H NMR
(400 MHz, CDCl3): d=7.57 (d, J=7.2 Hz, 1.05H), 7.38 (t,
J=7.6 Hz, 1.14H), 7.12–7.33 (m, 11.58H), 7.02 (t, J=8.0 Hz,
0.55H), 6.92–6.94 (m, 2.08H), 6.85 (m, 0.49H), 6.78–6.79
(m, 0.49H), 6.71–6.73 (m, 0.49), 6.64–6.67 (m, 0.53H), 6.56–
6.57 (m, 0.51H), 6.50–6.52 (m, 0.52H), 4.36 (s, 1.03H), 4.12–
4.21 (m, 3.94H), 3.80 (s, 2.24H), 3.66 (s, 1.42H), 3.64 (s,
0.95H), 3.54 (s, 1.57H), 1.13–1.18 (m, 3H); 13C NMR
(100 MHz, CDCl3): d=171.2, 168.6, 159.3, 159.2, 158.7,
157.8, 142.1, 141.4, 139.2, 138.9, 137.9, 137.6, 129.4, 128.9,
128.8, 128.7, 128.6, 128.6, 128.4, 128.3, 128.2, 127.5, 127.4,
126.5, 126.5, 123.5, 123.5, 116.3, 115.6, 112.4, 112.3, 111.0,
108.5, 60.2, 59.9, 55.5, 55.1, 55.1, 54.0, 38.7, 38.3, 14.6, 14.4;
HR-MS (ESI): m/z=514.2368, calcd. for C33H33NO3Na [M+
Na]: 514.2353.
Ethyl 3-(dibenzylamino)-2-(3-fluorophenyl)-4-phenylbut-
2-enoate (6g): The title compound was prepared according
to the general procedure and purified by flash column chro-
matography to give a white solid; yield: 221.2 mg (92%);
1
1
Z/E=44/56 (determined by H NMR); H NMR (400 MHz,
CDCl3): d=7.57 (d, J=7.2 Hz, 1.14H), 7.39 (t, J=7.6 Hz,
1.26H), 7.15–7.32 (m, 11.26H), 7.01–7.07 (m, 1.13H), 6.84–
6.95 (m, 3.13H), 6.76–6.81 (m, 0.55H), 6.64–6.66 (m,
0.53H), 6.54–6.57 (m, 0.53H), 4.39 (s, 1.14H), 4.12–4.22 (m,
3.72H), 3.77 (s, 2.29H), 3.63 (s, 0.88H), 1.13–1.18 (m, 3H);
13C NMR (100 MHz, CDCl3): d=170.6, 168.0, 163.7, 161.3,
160.4, 158.7, 143.1, 143.1, 142.4, 142.3, 139.0, 138.4, 137.6,
137.2, 129.4, 129.3, 129.2, 129.1, 128.7, 128.7, 128.6, 128.6,
128.3, 128.2, 127.7, 127.5, 126.9, 126.6, 118.1, 117.9, 117.7,
117.5, 113.3, 113.1, 112.9, 112.7, 110.2, 107.2, 60.3, 59.9, 55.7,
54.3, 38.7, 38.2, 14.6, 14.3; 19F NMR (376 MHz, CDCl3): d=
À114.05, À114.13; HR-MS (ESI): m/z=480.2330, calcd. for
C32H31FNO2 [M+H]: 480.2333.
Ethyl 2-(4-chlorophenyl)-3-(dibenzylamino)-4-phenylbut-
2-enoate (6h): The title compound was prepared according
to the general procedure and purified by flash column chro-
matography to give a white solid; yield: 241.1 mg (97%);
1
1
Z/E=42/58 (determined by H NMR); H NMR (400 MHz,
CDCl3): d=7.57 (d, J=7.6 Hz, 1.17H), 7.39 (t, J=7.6 Hz,
1.26H), 7.14–7.29 (m, 12.33H), 7.03 (d, J=8.0 Hz, 1.18H),
6.89–6.90 (m, 2.34H), 6.73 (d, J=8.0 Hz, 1.17H), 4.40 (s,
1.16H), 4.11–4.22 (m, 3.76H), 3.74 (s, 2.35H), 3.61 (s,
0.82H), 1.12–1.17 (m, 3H); 13C NMR (100 MHz, CDCl3):
d=170.7, 168.1, 160.3, 158.6, 139.4, 139.1, 138.7, 138.4, 137.6,
137.1, 132.4, 132.1, 131.5, 129.4, 128.7, 128.7, 128.6, 128.6,
128.3, 128.2, 128.1, 127.7, 127.5, 126.6, 110.2, 107.0, 60.3,
59.9, 55.7, 54.2, 38.7, 38.1, 14.6, 14.4; HR-MS (ESI): m/z=
496.2015, calcd. for C32H31ClNO2 [M+H]: 496.2038.
Ethyl 2-(3-chlorophenyl)-3-(dibenzylamino)-4-phenylbut-
2-enoate (6i): The title compound was prepared according to
the general procedure and purified by flash column chroma-
tography to give a white solid; yield: 243.7 mg (98%); Z/E=
41/59 (determined by 1H NMR); 1H NMR (400 MHz,
CDCl3): d=7.57 (d, J=7.2 Hz, 1.17H), 7.39 (t, J=7.6 Hz,
1.38H), 7.17–7.31 (m, 10.93H), 7.13 (s, 1.27H), 7.01–7.07
(m, 1.25H), 6.89–6.91 (m, 2.92H), 6.78–6.80 (m, 0.58H),
4.40 (s, 1.17H), 4.22 (s, 1.60H), 4.11–4.20 (m, 2.04H), 3.77
(s, 2.37H), 3.62 (s, 0.82H), 1.12–1.17 (m, 3H); 13C NMR
(100 MHz, CDCl3): d=170.5, 167.9, 160.7, 158.9, 142.7,
142.0, 139.0, 138.4, 137.5, 137.1, 133.6, 131.3, 130.7, 129.4,
129.4, 129.2, 129.1, 128.7, 128.7, 128.6, 128.6, 128.3, 128.2,
127.7, 127.5, 126.6, 126.4, 126.0, 109.9, 106.9, 60.3, 59.9, 55.7,
Ethyl 3-(dibenzylamino)-2-(4-fluorophenyl)-4-phenylbut-
2-enoate (6f): The title compound was prepared according
Adv. Synth. Catal. 0000, 000, 0 – 0
8
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54.4, 38.7, 38.2, 14.6, 14.3; HR-MS (ESI): m/z=496.2017,
calcd. for C32H31ClNO2 [M+H]: 496.2038.
C. Fargeau-Bellassoued, G. Haviari, J. P. Celerier, G.
Lhommet, J.-C. Gramain, D. Gardette, J. Org. Chem.
1999, 64, 3122; g) J. P. Michael, A. S. Parsons, Tetrahe-
dron 1999, 55, 10915; h) J. P. Michael, C. B. Koning,
G. D. Hosken, T. V. Stanbury, Tetrahedron 2001, 57,
9635.
Ethyl 2-(2-chlorophenyl)-3-(dibenzylamino)-4-phenylbut-
2-enoate (6j): The title compound was prepared according
to the general procedure and purified by flash column chro-
matography to give a white solid; yield: 240.9 mg (97%);
1
1
Z/E=43/57 (determined by H NMR); H NMR (400 MHz,
CDCl3): d=7.59 (d, J=7.6 Hz, 1.17H), 7.35–7.42 (m 1.63H),
7.13–7.31 (m, 12.29H), 7.06–7.10 (m, 0.70H), 6.86–6.92 (m,
2.92H), 6.58–6.60 (m, 0.57H), 4.72 (d, J=16.4 Hz, 0.58H),
4.01–4.27 (m, 3.89H), 3.49–3.62 (m, 0.85H), 3.24 (d, J=
14.8 Hz, 1.17H), 1.09–1.14 (m, 3H); 13C NMR (100 MHz,
CDCl3): d=169.6, 166.9, 162.0, 160.8, 139.7, 139.7, 139.1,
138.2, 137.6, 137.4, 136.5, 136.0, 133.6, 132.9, 129.4, 129.3,
128.8, 128.6, 128.6, 128.6, 128.5, 128.3, 128.1, 127.9, 127.6,
127.4, 126.6, 126.5, 126.4, 109.8, 104.8, 60.3, 59.7, 56.0, 53.9,
39.0, 37.4, 14.6, 14.3; HR-MS (ESI): m/z=496.2040, calcd.
for C32H31ClNO2 [M+H]: 496.2038.
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Ethyl 3-(dibenzylamino)-2-(naphthalen-2-yl)-4-phenylbut-
2-enoate (6k): The title compound was prepared according
to the general procedure and purified by flash column chro-
matography to give a white solid; yield: 243.5 mg (95%);
1
1
Z/E=36/64 (determined by H NMR); H NMR (400 MHz,
CDCl3): d=7.60–7.77 (m, 4.07H), 7.36–7.43 (m, 4.22H),
7.11–7.33 (m, 11.46H), 6.88–6.90 (m, 2.62H), 4.48 (s,
1.29H), 4.26 (s, 1.36H), 4.14–4.21 (m, 2.05H), 3.73 (s,
2.61H), 3.66 (s, 0.72H), 1.12–1.16 (m, 3H); 13C NMR
(100 MHz, CDCl3): d=171.1, 168.6, 160.1, 158.5, 139.3,
138.8, 138.5, 137.8, 137.6, 137.4, 133.5, 133.3, 132.2, 131.9,
130.0, 129.6, 129.6, 129.3, 128.8, 128.7, 128.7, 128.6, 128.5,
128.4, 128.3, 128.0, 127.9, 127.6, 127.5, 127.4, 127.3, 126.6,
126.5, 125.8, 125.7, 125.5, 125.5, 111.2, 108.3, 60.3, 59.9, 55.6,
54.3, 38.8, 38.2, 14.6, 14.4; HR-MS (ESI): m/z=512.2561,
calcd. for C36H34NO2 [M+H]: 512.2584.
[4] During the preparation of this manuscript, a Rh/Cu-bi-
metalic catalytic three-component reaction with aro-
matic amines was described: a) N.-N. Wang, L.-R.
Huang, W.-J. Hao, T.-S. Zhang, G. Li, S.-J. Tu, B. Jiang,
Org. Lett. 2016, 18, 1298. For an intramolecular reac-
tion: b) K. Liu, C. Zhu, J. Min, S. Peng, G. Xu, J. Sun,
Angew. Chem. 2015, 127, 13154; Angew. Chem. Int. Ed.
2015, 54, 12962.
Acknowledgements
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Beckwith, Chem. Rev. 2003, 103, 2861; b) H. M. L.
Davies, J. R. Manning, Nature 2008, 451, 417; c) M. M.
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This research was financially supported by CAS Interdiscipli-
nary Innovation Team and the National Natural Science
Foundation of China (21672199).
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Copper-Catalyzed Difunctionalization of Terminal Alkynes
with Diazo Esters and Amines to Construct b-Enamino
Esters
11
Adv. Synth. Catal. 2016, 358, 1 – 11
Bao Gao, Hanmin Huang*
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