Copper-catalyzed synthesis of α,β-unsaturated acylamides via direct amidation from cinnamic acids and N-substituted formamides

Article abstract of DOI:10.1016/j.tet.2013.06.078

A highly effective synthesis of α,β-unsaturated acylamides is reported for the first time via copper-catalyzed direct amidation between readily available cinnamic acids and N-substituted formamides. The protocol was easily accessible and practical.

Full text of DOI:10.1016/j.tet.2013.06.078

Accepted Manuscript
Copper-Catalyzed Synthesis of #, #-Unsaturated Acylamides via Direct Amidation
from Cinnamic Acids and N-Substituted Formamides
Hong Yan, Hailong Yang, Linhua Lu, Defu Liu, Guangwei Rong, Jincheng Mao
PII:
S0040-4020(13)01037-5
10.1016/j.tet.2013.06.078
TET 24554
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 20 April 2013
Revised Date: 17 June 2013
Accepted Date: 24 June 2013
Please cite this article as: Yan H, Yang H, Lu L, Liu D, Rong G, Mao J, Copper-Catalyzed Synthesis of
#, #-Unsaturated Acylamides via Direct Amidation from Cinnamic Acids and N-Substituted Formamides,
Tetrahedron (2013), doi: 10.1016/j.tet.2013.06.078.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Copper-Catalyzed Synthesis of α, β-
Unsaturated Acylamides via Direct
Amidation from Cinnamic Acids and N-
Substituted Formamides
Leave this area blank for abstract info.
Hong Yan, Hailong Yang, Linhua Lu, Defu Liu, Guangwei Rong and Jincheng Mao*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and
Materials Science, Soochow University, Suzhou 215123, P. R. China
O
O
O
CuSO4 (20 mol%)
R1
R1
N
+
OH
H
N
R
DTBP (2 equiv)
100-140 oC, 12-48 h, Ar
R
R2
R2
up to 98%

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Copper-Catalyzed Synthesis of α, β-Unsaturated Acylamides via Direct Amidation
from Cinnamic Acids and N-Substituted Formamides
Hong Yan, Hailong Yang, Linhua Lu, Defu Liu, Guangwei Rong and Jincheng Mao*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou
215123, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A highly effective synthesis of α, β-unsaturated acylamides is reported for the first time via
copper-catalyzed direct amidation between readily available cinnamic acids and N-substituted
formamides. The protocol was easily accessible and practical.
2009 Elsevier Ltd. All rights reserved.
Available online
Keywords:
Amidation
Cinnamamide
N-substituted formamide
Ligand-free
Cinnamic acid
19th century.1-7 For example, as shown in Figure 1, N-(2-
hydroxyethyl)cinnamamide (A) was found to show good
1. Introduction
O
anticonvulsant activity and also low toxicity;2 The natural
piperidine derivative (B) showed good insecticidal activity
against the fall armyworm, S. frugiperda.3 The genus piperaceae
molecules (C) have been widely studied, due to the biological
properties of secondary metabolites from these plants.4
Compounds (D) represent a novel series of potent small molecule
inhibitors that not only have excellent in vitro profiles but also
have activity in vivo.5 In addition, in the course of screening
compounds for pharmacological action, it was observed that α-
phenyl-N,N-diethyl cinnamamide potentiated nembutal hypnosis
in rats.6 Furthermore, N,N-dimethylcinnamamide compounds are
potentially antidepressant. It is noteworthy that the trans-isomers
possess much more pronounced biological activity than do the
cis-isomers.7 Therefore, the essentially pure trans-isomers are
preferred.
O
N
OH
N
H
O
O
(A)
(B)
O
R1
HOOC
N
O
R2
O
N
O
RO
O
N
NH
R3
(D)
(C)
Figure 1. Examples of molecules containing cinnamamide moiety
O
O
O
α, β-Unsaturated acylamides, such as cinnamamides and their
derivatives, possess many biological activities such as
anticonvulsant, antidepressant, analgesic, antiestrogenic and
antifungal properties which have been widely applied in
agricultural, pharmaceutical and synthetic chemistry since the
R1
[Cu], [O]
OH
R1
N
+
R
H
N
R
R2
R2
Scheme 1. Our protocol to prepare cinnamamides via coupling between
cinnamic acids with N-substituted formamides.
———
* Corresponding author. Tel (Fax): +86 512 65880403. E-mail address: jcmao@suda.edu.cn (J. Mao)

ACCEPTED MANUSCRIPT
2
Tetrahedron
In view of the preparation of cinnamamides, the routine
oC under argon atmosphere and N,N-dimethylcinnamamide was
acquired in the yield of 48% (Table 1, entry 1). Among the
copper sources screened, most of the copper salts gave moderate
yields (entries 1–12). Notably, CuSO4 and Cu(OTf)2 showed their
best catalytic properties for the amidation (entries 11–12). In
view of the cost of these two salts, we chose readily available
CuSO4 as the ideal catalyst. Furthermore, various oxidants were
studied, including (NH4)2S2O8, tert-butyl hydroperoxide (TBHP)
and dicumyl peroxide (DCP) (entries 13–16), and DTBP proved
the best. We found that temperatures in the range from 100 to
approach is cascade chlorination of cinnamic acid and amination
with secondary amines. These chlorination reagents, such as
phosphoryl chloride or thionyl chloride, are usually toxic,
volatile, irritative and corrosive. Therefore, a more practical and
accessible way to synthesize cinnamamides is highly desirable.
Recently, our group reported a copper-catalyzed decarboxylative
C–H functionalization between cinnamic acids and benzylic
molecules.8 As a further extension of our work, we have
developed an example of copper-catalyzed direct amidation from
cinnamic acids and N-substituted formamides to afford various
cinnamamides as shown in Scheme 1. It is noteworthy that in this
study, N-substituted formamides were used not only as the
solvent, but also as an amine source.9 Actually, N,N-
dimethylformamide (DMF) has been extensively applied to the
o
150 C did not influence the model reaction greatly (entries 17–
o
20). However, when the reaction was carried out at 80 C, no
reaction was observed (entry 21). Less copper catalyst led to
lower yields of the desired product (entries 22–23). The reaction
performed in air afforded a reduced yield of 3aa (entry 24). The
control experiments showed that CuSO4 or DTBP alone could not
catalyze the reaction (entries 25–26).
preparation
of
amides
in
different
reactions:
a)
aminocarbonylation of aryl halides using DMF as an amide
source;10 b) direct aminocarbonylation of azoles with DMF via
C–H activation;11 c) tandem chlorination and amidation of
carboxylic acids in DMF;12 d) direct amidation of alcohols or
aldehydes with DMF.13
Table 2. Copper-catalyzed amidation between different cinnamic acids (1)
with DMF (2a) a
O
CuSO4 (20 mol%)
COOH
+
2. Results and discussion
2a
R
N
R
DTBP (2 equiv)
100-140 oC, 12 h, Ar
3
1
Table 1. Optimization of reaction conditions for the synthesis of
O
a
O
N
O
N
cinnamamide (3aa)
Me
N
O2N
O
3ga, 77% (89%)[b]
3ma, 63%[b] (E:Z=10:1)
3aa, 83% (82%)[b]
O
COOH
Copper cat.
O
N
+
H
N
O
O
N
Oxidant, 12 h, Ar
N
N
3aa
1a
2a
Cl
MeO
3ha, 71% (73%)[b]
OMe
3ba, 77% (71%)[b]
3na, 82%[b]
T
Yield
(%)b
48
62
64
30
47
9
entry
Copper cat. (mol%)
Oxidant
(oC)
140
O
O
O
1
2
CuI (20)
CuBr (20)
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
(NH4)2S2O8
TBHP
BQ
O
N
N
N
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
150
130
120
100
80
F
CuCl (20)
3ca, 81% (85%)[b]
3ia, 89% (80%)[b]
3oa, 86% (76%)[b]
3
O
O
Cu2O (20)
4
O
MeO
S
N
Cu powder (20)
CuO (20)
N
N
5
N
F3C
6
3da, 65% (77%)[b]
3pa, 71% (91%)[b]
3ja, 80% (94%)[b]
CuBr2 (20)
41
45
62
56
82
82
40
75
ND
58
80
75
78
83
NR
50
40
71
NR
NR
7
O
O
O
CuCl2•2H2O (20)
Cu(OAc)2•H2O (20)
Cu(acac)2•H2O (20)
CuSO4 (20)
Cu(OTf)2 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (20)
CuSO4 (10)
CuSO4 (5)
8
MeO
N
N
9
MeO
3ka, 76% (80%)[b]
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24c
3qa, 42% (58%)[b]
3ea, 88% (98%)[b]
O
O
O
MeO
N
N
N
MeO
Me
3fa, 83% (69%)[b]
OMe
3la, 75% (77%)[b]
3ra, 90% (86%)[b]
a
Catalytic conditions: cinnamic acid (1a) (0.3 mmol), DMF (2a) (2 mL),
DCP
CuSO4 (20 mol%), DTBP (2 equiv.), 100 oC, 24 h, Ar. Isolated yield based on
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
–
cinnamic acid; All of the products were pure trans-isomers. b 140 oC, 12h.
With the optimized conditions in hand, various cinnamic acids
were explored for the amidation reactions at 100–140 oC as
shown in Table 2. We were pleased to observe that amidation of
the cinnamic acids with electron-withdrawing groups such as 4-
Cl, 4-F and 4-CF3 groups as well as electron-donating groups
such as methyl, methoxyl and isopropyl could offer good to
excellent yields of corresponding products (3ba-3la), and all of
the products were the pure trans-isomers. However, it is strange
to observe that the reaction of (E)-4-nitrocinnamic acid afforded
the desired product with mixed isomers (E/Z=10:1) (3ma). 1-
Naphthylcrylic acid was also a suitable substrate and the desired
product was obtained in 82% yield (3na). Subsequently, various
heterocyclic acrylic acids were investigated in the reaction. 2-
100
100
100
100
100
CuSO4 (20)
–
CuSO4 (20)
25
26
a Catalytic conditions: cinnamic acid (1a) (0.3 mmol), Copper cat., DMF (2
mL), oxidant (2 equiv), 80-140 oC, 12 h, Ar. b Isolated yield based on
cinnamic acid. c In air.
Initially, the model reaction of cinnamic acid (0.3 mmol) with
2 mL of DMF was performed in the presence of CuI (20 mol %)
and di-tert-butyl peroxide (DTBP) (2 equiv) as the oxidant at 140

ACCEPTED MANUSCRIPT
3
S
O
O
Furylcrylic acid, 2-thienylcrylic acid and 3-pyridylcrylic acid
S
CuSO4 (20 mol%)
+
N
N
OH
+
afforded the corresponding products in moderate to good yields
(3oa, 3pa and 3qa). When the α-hydrogen of cinnamic acid was
substituted by methyl group, the reaction still occurred smoothly
(3ra).
H
N
DTBP (2 equiv)
140 oC, 12 h, Ar
a
b
38%
N.O
O
O
H
N
CuSO4 (20 mol%)
N
OH
+
DTBP (2 equiv)
140 oC, 24 h, Ar
O
O
< 5%
Table 3. Copper-catalyzed amidation between 1e with different N-substituted
formamides (2)a
O
O
COOH
CuSO4 (20 mol%)
+
N
H
N
TEMPO (2 equiv)
DTBP (2 equiv)
100-140 oC, 12 h, Ar
O
O
Isolated yield
No TEMPO 83%
COOH
R1
CuSO4 (20 mol%)
N
R1
+
H
N
R2
100 o
140 oC
C
Trace
15%
DTBP (2 equiv)
100-140 oC, 12-48 h, Ar
R2
1e
2
3
O
N
O
O
N
Scheme 4. Control experiments and effect of radical inhibitor.
N
H
3eb, 84% (71%)[b]
3ee, 63%
3eh, 19%[c]
To gain more understanding of this reaction, several
experiments were performed (Scheme 4). First, N,N-
dimethylthioformamide was employed instead of DMF as the
reactant, affording only product a in 38% yield whereas
decarbonylated product b was not observed. This indicated that
the carbonyl group of cinnamamide came from cinnamic acid
possibly.9 When morpholine was used to replace DMF, only a
trace of cinnamamide was detected by LC-MS. Radical
O
O
O
N
N
O
N
3ec, 76% (63%)[b]
3ei, N.R
3ef, 42%[d]
O
O
N
NH2
o
scavenger TEMPO completely inhibited the reaction at 100 C
3eg, 21%[d]
3ed, 54%
whereas the reaction was seriously suppressed at 140 oC. We
believe that it might involve a participation of radicals in the
catalytic cycle of the reaction.
a
Reaction conditions: 4-isopropylcinnamic acid (1e) (0.3 mmol), N-
substituted formamide (2) (2 mL), CuSO4 (20 mol%), DTBP (2 equiv.), 140
oC, 12 h, Ar. Isolated yield based on cinnamic acid. b 100 oC, 24 h c 48 h. d 24
h
O
O
Then, we examined a series of N-substituted formamide
derivatives and the results were listed in Table 3. It was showed
that the longer carbon chain on the N atom resulted in the lower
yields of cinnamamides (3ea vs 3eb and 3ec). On the other hand,
+
O
COOH
O
HO
+
N
CuII
IV
N-formylpyrrolidine,
N-formylpiperidine
and
N-
O
H+
formylmorpholine afforded the desired products in moderate
yields (3ed, 3ee and 3ef). N-Methylformanilide was not suitable
for our methodology which probably attributed to the difficulty
to destroy the strong conjugation between the amide group and
phenyl ring (3ei).13 For formamide and N-methylformamide,
neither of them exhibited good reactivities in the reactions with
4-propylcinnamic acid (3eg and 3eh).
H
N
H++t-BuO
t-BuO
N
CuI
t-BuOH
O
+
CO
SET
N
O
CuII
O
I
O
CuII
II
O
O
N
III
O
COOH
NO2
O
CuSO4 (20 mol%)
N
+
H
N
DTBP (2 equiv)
140 oC, 12 h, Ar
Scheme 5. The possible mechanism.
NO2
62%
O
O
O
O
CuSO4 (20 mol%)
DTBP (2 equiv)
Scheme 2. Copper-catalyzed amidation of 2-nitrobenzoic acid with DMF
N
N
O
+
140 oC,12 h, Ar
H
N
N
O
O
COOH
CuSO4 (20 mol%)
DTBP (2 equiv), Ar
I
+
75%
H
N
N
O
O
CuSO4 (20 mol%)
DTBP (2 equiv)
O
O
100 oC, 24 h
140 oC, 12 h
74%
84%
+
H
140 oC,12 h, Ar
N.R
Scheme 3. Copper-catalyzed amidation between 1a and N,N-
diethylformamide.
Scheme 6. Control experiments to prove the mechanism
To broaden the scope of amidation, 2-nitrobenzoic acid
afforded the desired product with a moderate yield using our
Based on previous observations, a plausible mechanism is
proposed in Scheme 5. Cu(II) firstly oxidized DTBP and
cinnamic acid to create the peroxyester I.16-18 At the same time,
amino radical was generated in situ from DMF.13 Secondly, Cu(I)
reduced amino radical to the intermediate II through a single-
catalytic
system
(Scheme
2).14
Furthermore,
N,N-
diethylcinnamamide which showed good activity against
Aspergillus niger15 was obtained in good yield by direct copper-
catalyzed amidation between cinnamic acid and N,N-
dimethylformamide (Scheme 3).
electron transfer process.19 Finally, peroxyester
I
and

ACCEPTED MANUSCRIPT
4
Tetrahedron
White solid, m.p. 118-120 oC; 1H NMR (400 MHz, CDCl3) δ:
7.61 (d, J = 16.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.33 (d, J =
8.0 Hz, 2H), 6.86 (d, J = 16.0 Hz, 1H), 3.16 (s, 3H), 3.06 (s, 3H);
13C NMR (75 MHz, CDCl3) δ: 166.3, 140.9, 135.2, 133.7, 128.9,
128.9, 117.9, 37.3, 35.9. HRMS ESI (m/z): [M+Na]+ calcd for
C11H12ClNNaO, 232.0500; found, 232.0500.
intermediate II produced the cinnamamide via addition-
elimination. To prove the hypothesis, we exclusively prepared
peroxyester I20 and treated it with DMF under the foregoing
optimized conditions. The expected product was obtained in 75%
yield as shown in Scheme 6. However, compared with
peroxyester I, ethyl cinnamate was not reacted at all in the same
condition.
(E)-3-(4-Fluorophenyl)-N,N-dimethylacrylamide (3ca)
White solid, m.p. 94-96 oC;1H NMR (300 MHz, CDCl3) δ: 7.64
(d, J = 15.0 Hz, 1H), 7.54-7.49 (m, 2H), 7.09-7.02 (m, 2H), 6.83
(d, J = 15.0 Hz, 1H), 3.17 (s, 3H), 3.07 (s, 3H); 13C NMR (75
MHz, CDCl3) δ: 166.4, 163.3 (d, J = 201.8 Hz), 140.9, 131.4 (d,
J = 2.3 Hz), 129.4 (d, J = 8.3 Hz), 117.0, 115.7 (d, J = 21.8 Hz),
37.3, 35.8. HRMS ESI (m/z): [M+H]+ calcd for C11H13FNO,
194.0976; found, 194.0987.
3. Conclusions
In conclusion, we have developed an efficient and direct
method for the synthesis of α, β-unsaturated acylamides from
cinnamic acids and N-substituted formamides. Both electron-
withdrawing and electron-donating groups of the substrates used
are well tolerated. In addition, 2-nitrobenzoic acid is also suitable
for our catalyst system. It is noteworthy that our protocol is easily
accessible and practical: 1) the readily available cinnamic acids
could be directly used as the starting materials; 2) our catalyst
system is low-cost and ligand-free; 3) the catalytic reaction is
highly selective and the desired cinnamic acids were obtained
exclusively. Further studies on the mechanism and the
application of the reactions are currently in progress.
(E)-N,N-Dimethyl-3-(4-(trifluoromethyl)phenyl)acrylamide
(3da)
1
White solid, m.p. 104-106 oC; H NMR (400 MHz, CDCl3) δ:
7.67 (d, J = 16.0 Hz, 1H), 7.62 (s, 4H), 6.97 (d, J = 16.0 Hz, 1H),
3.19 (s, 3H), 3.08 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.0,
139.6 (d, J = 136.5 Hz), 131.0 (d, J = 32.3 Hz), 127.9, 125.7 (q, J
= 3.5 Hz), 122.1, 119.9, 37.4, 35.9. HRMS ESI (m/z): [M+Na]+
calcd for C12H12F3NNaO, 266.0763; found, 266.0766.
4. Experiment
4.1 General information
All reactions were carried out under an argon atmosphere
condition. Cupric sulfate was purchased from Alfa. Various
cinnamic acids and N-substituted formamides were purchased
from Aldrich, Acros or Alfa. Column chromatography was
generally performed on silica gel (100-200 mesh) and reactions
were monitored by thin layer chromatography (TLC) using UV
(E)-3-(4-Isopropylphenyl)-N,N-dimethylacrylamide (3ea)
White solid, m.p. 42-44 oC; 1H NMR (400 MHz, CDCl3) δ: 7.65
(d, J = 16.0 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz,
2H), 6.85 (d, J = 16.0 Hz, 1H), 3.16 (s, 3H), 3.06 (s, 3H), 2.95-
2.86 (m, 1H), 1.25 (d, J = 8.0 Hz, 6H); 13C NMR (75 MHz,
CDCl3) δ: 166.8, 150.6, 142.2, 132.9, 127.7, 126.8, 116.3, 37.3,
35.8, 33.9, 23.7. HRMS ESI (m/z): [M+Na]+ calcd for
C14H19NNaO, 240.1359; found, 240.1364.
1
light (254 nm) to visualize the course of the reactions. The H
(300 MHz or 400 MHz) and 13C NMR (75 MHz or 100 MHz)
data were recorded on Varian 300 M or 400 M spectrometers
using CDCl3 as solvent. The chemical shifts (δ) are reported in
ppm and coupling constants (J) in Hz. 1H NMR spectra was
recorded with tetramethylsilane (δ = 0.00 ppm) as internal
reference; 13C NMR spectra was recorded with CDCl3 (δ =
77.000 ppm) or DMSO-d6 (δ = 39.500 ppm) as internal reference.
ESI-MS and HRMS were performed by the State-authorized
Analytical Center in Soochow university.
(E)-N,N-Dimethyl-3-(p-tolyl)acrylamide (3fa)
White solid, m.p. 98-100 oC; 1H NMR (400 MHz, CDCl3) δ:
7.64 (d, J = 16.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.17 (d, J =
8.0 Hz, 2H), 6.84 (d, J = 16.0 Hz, 1H), 3.15 (s, 3H), 3.05 (s, 3H),
2.36 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.9, 142.3, 139.8,
132.6, 129.5, 127.7, 116.3, 37.4, 35.9, 21.4. HRMS ESI (m/z):
[M+Na]+ calcd for C12H15NNaO, 212.1046; found, 212.1053.
4.2 General procedure for copper-catalyzed direct amidation
between cinnamic acid and N-substituted formamide:
(E)-N,N-Dimethyl-3-(m-tolyl)acrylamide (3ga)
CuSO4 (0.06 mmol) and cinnamic acid (0.3 mmol) were added to
a Schlenk tube equipped with a magnetic stir bar under argon
atmosphere. Then N-substituted formamide (2.0 mL) and DTBP
(di-tert-butyl peroxide, 0.6 mmol) were added under Ar. The
resulting reaction mixture was kept stirring until TLC monitoring
indicated the complete disappearance of the starting material. At
the end of the reaction, the reaction mixture was cooled to room
temperature and was diluted with ethyl acetate and water was
added. The combined organic phase was dried over anhydrous
Na2SO4. After removal of the solvent, the residue was subjected
to column chromatography on silica gel using ethyl acetate and
petroleum ether mixtures to afford the corresponding product.
Colorless oil; 1H NMR (300 MHz, CDCl3) δ: 7.65 (d, J = 15.0
Hz, 1H), 7.33-7.23 (m, 3H), 7.17 (s, 1H), 6.88 (d, J = 15.0 Hz,
1H), 3.17 (s, 3H), 3.06 (s, 3H), 2.36 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ: 166.6, 142.3, 138.2, 135.1, 130.2, 128.5, 128.2, 124.8,
117.0, 37.2, 35.7, 21.2. HRMS ESI (m/z): [M+Na]+ calcd for
C12H15NNaO, 212.1046; found, 212.1054.
(E)-3-(4-Methoxyphenyl)-N,N-dimethylacrylamide (3ha)
White solid, m.p. 87-89 oC; 1H NMR (300 MHz, CDCl3) δ: 7.64
(d, J = 15.0 Hz, 1H), 7.48 (d, J = 9.0 Hz, 2H), 6.89 (d, J = 9.0 Hz,
2H), 6.76 (d, J = 15.0 Hz, 1H), 3.81 (s, 3H), 3.15 (s, 3H), 3.05 (s,
3H); 13C NMR (100 MHz, CDCl3) δ: 166.9, 160.7, 141.9, 129.2,
127.9, 114.8, 114.1, 55.2, 37.3, 35.8. HRMS ESI (m/z): [M+H]+
calcd for C12H16NO2, 206.1176; found, 206.1175.
(E)-N,N-Dimethylcinnamamide (3aa)
o
White solid, m.p. 96-98 C; 1H NMR (300 MHz, CDCl3) δ: 7.68
(d, J = 15.0 Hz, 1H), 7.52 (s, 2H), 7.35 (s, 2H), 6.90 (d, J = 15.0
Hz, 1H), 3.17 (s,3H), 3.07 (s,3H); 13C NMR (75 MHz, CDCl3) δ:
166.7, 142.3, 135.3, 129.5, 128.8, 127.8, 117.4, 37.4, 35.9. MS
ESI (m/z): [M+H]+ calcd for C11H14NO, 176.1; found, 176.1.
(E)-3-(2-Methoxyphenyl)-N,N-dimethylacrylamide (3ia)
White solid, m.p. 70-72oC;1H NMR (300 MHz, CDCl3) δ: 7.92
(d, J = 15.0 Hz, 1H), 7.49 (d, J = 6.0 Hz, 1H), 7.30-7.27 (m, 1H),
7.02-6.89 (m, 3H), 3.86 (s, 3H), 3.15 (s, 3H), 3.05 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ: 167.1, 157.9, 137.6, 130.4, 128.7,
(E)-3-(4-Chlorophenyl)-N,N-dimethylacrylamide (3ba)

ACCEPTED MANUSCRIPT
5
124.1, 120.4, 118.2, 110.9, 55.2, 37.2, 35.6. HRMS ESI (m/z):
[M+H]+ calcd for C9H12NOS, 182.0634; found, 182.0639.
[M+Na]+ calcd for C12H15NNaO2, 228.0995; found, 228.1003.
(E)-N,N-Dimethyl-3-(pyridin-3-yl)acrylamide (3qa)
(E)-3-(3-Methoxyphenyl)-N,N-dimethylacrylamide (3ja)
Colorless oil. H NMR (400 MHz, CDCl3) δ: 7.63 (d, J = 16.0
Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 4.0 Hz, 1H), 7.04
(s, 1H), 6.91-6.85 (m, 2H), 3.83 (s, 3H), 3.16 (s, 3H), 3.06 (s,
3H); 13C NMR (75 MHz, CDCl3) δ: 166.6, 159.8, 142.2, 136.7,
129.7, 120.3, 117.7, 115.0, 113.1, 55.3, 37.4, 35.9. HRMS ESI
(m/z): [M+H]+ calcd for C12H16NO2, 206.1176; found, 206.1179.
Yellow solid, m.p. 100-102 oC; 1H NMR (400 MHz, CDCl3) δ:
8.76 (d, J = 1.6.0 Hz, 1H), 8.58-8.56 (m, 1H), 7.84-7.81 (m, 1H),
7.65 (d, J = 16.0 Hz, 1H), 7.33-7.30 (m, 1H), 6.98 (d, J = 16.0 Hz,
1H), 3.19 (s, 3H), 3.08 (s, 3H); 13C NMR (75 MHz, CDCl3) δ:
165.9, 150.1, 149.1, 138.5, 134.2, 131.0, 123.5, 119.5, 37.3, 35.9.
HRMS ESI (m/z): [M+H]+ calcd for C10H13N2O, 177.1022; found,
177.1014.
1
(E)-3-(3,4-Dimethoxyphenyl)-N,N-dimethylacrylamide (3ka)
White solid, m.p. 93-95 oC; 1H NMR (300 MHz, CDCl3) δ: 7.61
(d, J = 15.0 Hz, 1H), 7.11 (d, J = 6.0 Hz, 1H), 7.03 (s, 1H), 6.85
(d, J = 6.0 Hz, 1H), 6.75 (d, J = 15.0 Hz, 1H), 3.91 (d, J = 3.0 Hz,
6H), 3.17 (s, 3H), 3.06 (s, 3H); 13C NMR (75 MHz, CDCl3) δ:
166.9, 150.4, 149.0, 142.3, 128.3, 121.7, 115.1, 111.1, 109.9,
55.9, 37.4, 35.9. HRMS ESI (m/z): [M+H]+ calcd for C13H18NO3,
236.1281; found, 236.1285.
(E)-N,N,2-Trimethyl-3-phenylacrylamide (3ra)
Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.40-7.33 (m, 4H),
7.30-7.28 (m, 1H), 6.55 (s, 1H), 3.07 (s, 6H), 2.12 (s, 3H); 13
NMR (75 MHz, CDCl3) δ: 173.6, 136.0, 133.3, 129.6, 129.0,
128.3, 127.3, 38.7, 34.9, 15.9. HRMS ESI (m/z): [M+H]+ calcd
for C12H16NO, 190.1226; found, 190.1231.
C
(E)-N,N-Diethyl-3-(4-isopropylphenyl)acrylamide (3eb)
Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.69 (d, J = 16.0
Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.78
(d, J = 16.0 Hz, 1H), 3.52-3.44 (m, 4H), 2.97- 2.86 (m, 1H), 1.25
(d, J = 8.0 Hz, 9H), 1.19 (t, J = 6.0 Hz, 3H );13C NMR (75 MHz,
CDCl3) δ: 165.8, 150.5, 142.2, 133.0, 127.7, 126.8, 116.7, 42.2,
41.0, 33.9, 23.7, 15.0, 13.2. HRMS ESI (m/z): [M+H]+ calcd for
C16H24NO, 246.1852; found, 246.1854.
(E)-N,N-Dimethyl-3-(3,4,5-trimethoxyphenyl)acrylamide (3la)
White solid, m.p. 110-112 oC; 1H NMR (300 MHz, CDCl3) δ:
7.50 (d, J = 15.0 Hz, 1H), 6.70 (d, J = 18.0 Hz, 3H), 3.80 (d, J =
6.0 Hz, 9H), 3.10 (s, 3H), 2.98 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ: 166.4, 153.2, 142.2, 139.3, 130.7, 116.5, 104.8, 60.7,
56.0, 37.3, 35.8. HRMS ESI (m/z): [M+H]+ calcd for C14H20NO4,
266.1387; found, 266.1395.
(E)-N,N-Dibutyl-3-(4-isopropylphenyl)acrylamide (3ec)
Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.68 (d, J = 16.0
Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.79
(d, J = 16.0 Hz, 1H), 3.44-3.37 (m, 4H), 2.97-2.87 (m, 1H), 1.66-
1.54 (m, 4H), 1.42-1.31 (m, 4H), 1.26 (d, J = 8.0 Hz, 6H), 0.99-
0.93 (m, 6H); 13C NMR (75 MHz, CDCl3) δ: 166.2, 150.5, 142.1,
133.2, 127.8, 126.8, 116.8, 47.9, 46.7, 34.0, 31.9, 30.1, 23.8, 20.3,
20.1, 13.9, 13.8. HRMS ESI (m/z): [M+H]+ calcd for C20H32NO,
302.2478; found, 302.2468.
N,N-Dimethyl-3-(4-nitrophenyl)acrylamide (3ma)
Yellow solid, m.p. 174-180 oC. (E)-N,N-Dimethyl-3-(4-
nitrophenyl)acrylamide: 1H NMR (400 MHz, CDCl3) δ: 8.23 (d,
J = 8.0 Hz, 2H), 7.71-7.66 (m, 3H), 7.04 (d, J = 16.0 Hz, 1H),
3.21 (s, 3H), 3.10 (s, 3H); (Z)-N,N-Dimethyl-3-(4-
1
nitrophenyl)acrylamide: H NMR (400 MHz, CDCl3) δ: 8.18 (d,
J = 8.0 Hz, 2H), 7.55 (d, J = 12.0 Hz, 2H), 6.72 (d, J = 12.0 Hz,
1H), 6.31 (d, J = 12.0 Hz, 1H), 3.01 (s, 3H), 2.91 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ: 165.6, 148.0, 141.5, 139.5, 128.3,
124.0, 121.7, 37.4, 36.0. HRMS ESI (m/z): [M+H]+ calcd for
C11H13N2O3, 221.0921; found, 221.0920.
(E)-3-(4-Isopropylphenyl)-1-(pyrrolidin-1-yl)prop-2-en-1-one
(3ed)
Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.68 (d, J = 16.0
Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.69
(d, J = 16.0 Hz, 1H), 3.64-3.57 (m, 4H), 2.97-2.86 (m, 1H), 2.03-
(E)-N,N-Dimethyl-3-(naphthalen-1-yl)acrylamide (3na)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ: 8.49 (d, J =
16.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz, 2H),
7.70 (d, J = 8.0 Hz, 1H), 7.57-7.50 (m, 2H), 7.49-7.44 (m, 1H),
6.94 (d, J = 16.0 Hz, 1H), 3.18 (s, 3H), 3.10 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ: 166.6, 139.7, 133.6, 133.1, 131.5, 129.7,
128.5, 126.6, 126.1, 125.4, 124.5, 123.8, 120.5, 37.5, 36.0.
HRMS ESI (m/z): [M+Na]+ calcd for C15H15NNaO, 248.1046;
found, 248.1046.
1.96 (m, 2H), 1.92-1.85 (m, 2H), 1.25 (d, J = 8.0 Hz, 6H); 13
C
NMR (75 MHz, CDCl3) δ: 164.8, 150.6, 141.6, 132.8, 127.8,
126.7, 117.7, 46.5, 45.9, 33.9, 26.0, 24.2, 23.7. HRMS ESI (m/z):
[M+H]+ calcd for C16H22NO, 244.1696; found, 244.1695.
(E)-3-(4-Isopropylphenyl)-1-(piperidin-1-yl)prop-2-en-1-one
(3ee)
White solid, m.p. 53-55 oC; 1H NMR (400 MHz, CDCl3) δ: 7.62
(d, J = 16.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz,
2H), 6.85 (d, J = 16.0 Hz, 1H), 3.62 (d, J = 28.0 Hz, 4H), 2.96-
2.86 (m, 1H), 1.69-1.66 (m, 2H), 1.61-1.57 (m, 4H), 1.25 (d, J =
8.0 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ: 165.51, 150.51,
142.14, 133.06, 127.69, 126.78, 116.63, 46.96, 43.29, 33.95,
26.70, 25.56, 24.60, 23.77. HRMS ESI (m/z): [M+H]+ calcd for
C17H24NO, 258.1852; found, 258.1841.
(E)-3-(Furan-2-yl)-N,N-dimethylacrylamide (3oa)
Brown oil. 1H NMR (300 MHz, CDCl3) δ: 7.47-7.36 (m, 2H),
6.81(d, J = 15.0 Hz, 1H), 6.55 (s, 1H), 6.45 (s, 1H), 3.16 (s, 3H),
3.06(s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.5, 151.6, 143.7,
129.1, 114.8, 113.7, 112.1, 37.3, 35.9. HRMS ESI (m/z):
[M+Na]+ calcd for C9H11NNaO2, 188.0687; found, 188.0694.
(E)-N,N-Dimethyl-3-(thiophen-2-yl)acrylamide (3pa)
1
Brown solid, m.p. 92-94 oC; H NMR (400 MHz, CDCl3) δ:
(E)-3-(4-Isopropylphenyl)-1-morpholinoprop-2-en-1-one (3ef)
Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.69 (d, J = 16.0
Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.80
(d, J = 16.0 Hz, 1H), 3.70 (d, J = 16.0 Hz, 8H), 2.97-2.87 (m,
1H), 1.26 (d, J = 8.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ:
7.79 (d, J = 16.0 Hz, 1H), 7.31 (d, J = 4.0 Hz, 1H), 7.21 (d, J =
4.0 Hz, 1H), 7.04-7.02 (m, 1H), 6.69 (d, J = 16.0 Hz, 1H), 3.14 (s,
3H), 3.05 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.2, 140.4,
135.0, 130.0, 127.8, 127.0, 116.0, 37.3, 35.8. HRMS ESI (m/z):

ACCEPTED MANUSCRIPT
6
Tetrahedron
2. Guan, L.-P.; Sui, X.; Deng, X.-Q.; Zhao, D.-H.; Qu, Y.-L.; Quan,
165.7, 150.9, 143.2, 132.7, 127.8, 126.9, 115.4, 66.8, 46.3, 46.1,
42.4, 34.0, 23.7. HRMS ESI (m/z): [M+H]+ calcd for C16H22NO2,
260.1645; found, 260.1646.
Z.-S. Med. Chem. Res. 2011, 20, 601–606.
3. Castral, T. C.; Matos, A. P.; Monteiro, J. L.; Araujo, F. M.;
Bondancia, T. M.; Batista-Pereira, L. G.; Fernandes, J. B.; Vieira,
P. C.; da Silva, M. F. G. F.; Correa, A. G. J. Agric. Food Chem.
2011, 59, 4822–4827.
4. (a) Kato, M. J.; Furlan, M. Pure Appl. Chem. 2007, 79, 529–538;
(b) Dyer, L. A.; Dodson, C. D.; Stireman, J. O.; Tobler, M. A.;
Smilanich, A. M.; Fincher, R. M.; Letourneau, D. K. J. Chem.
Ecol. 2003, 29, 2499–2514; (c) Richards, L. A.; Dyer, L. A.;
Smilanich, A. M.; Dodson, C. D. J. Chem. Ecol. 2010, 36, 1105–
1113.
5. Slee, D. H.; Romano, S. J.; Yu, J.; Nguyen, T. N.; John, J. K.;
Raheja, N. K.; Axe, F. U.; Jones, T. K.; Ripka, W. C. J. Med.
Chem. 2001, 44, 2094–2107.
6. Para, D.; Schwenk, E.; Villani, F.; Klingsbe, E. J. Am. Chem. Soc.
1950, 72, 3885–3886.
(E)-3-(4-Isopropylphenyl)acrylamide (3eg)
White solid, m.p. 195-197 oC; 1H NMR (400 MHz, DMSO-d6) δ:
7.51 (s, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 16.0 Hz, 1H),
7.27 (d, J = 8.0 Hz, 2H), 7.06 (s, 1H), 6.56 (d, J = 16.0 Hz, 1H),
2.94-2.84 (m, 1H), 1.19(d, J = 8.0 Hz, 6H); 13C NMR (100 MHz,
DMSO-d6) δ: 166.9, 150.1, 139.3, 132.6, 127.7, 126.9, 121.3,
33.4, 23.7. HRMS ESI (m/z): [M+Na]+ calcd for C12H15NNaO,
212.1046; found, 212.1042.
(E)-3-(4-Isopropylphenyl)-N-methylacrylamide (3eh)
7. Smith Kline & French Larboratoryties, 1968, Patent GB 1131727.
8. Yang, H.; Yan, H.; Sun, P.; Zhu, Y.; Lu, L.; Liu, D.; Rong, G.
Chem. Commun. 2012, 48, 7847–7849.
Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.61 (d, J = 16.0 Hz,
1H), 7.42 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 6.38 (d, J
= 16.0 Hz, 1H), 5.90 (s, 1H), 2.94-2.87 (m, 4H), 1.24 (d, J = 8.0
Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 167.2, 151.0, 140.9,
132.7, 128.0, 127.1, 119.8, 34.2, 26.7, 24.0. HRMS ESI (m/z):
[M+H]+ calcd for C13H18NO, 204.1383; found, 204.1384.
9. Ding, S.; Jiao, N. Angew. Chem. Int. Ed. 2012, 51, 9226–9237.
10. (a) Wan, Y.; Alterman, M.; Larhed, M.; Hallberg, A. J. Org.
Chem. 2002, 67, 6232–6235; (b) Hosoi, K.; Nozaki, K.; Hiyama,
T. Org. Lett. 2002, 4, 2849–2851; (c) Tambade, P. J.; Patil, Y. P.;
Bhanushali, M. J.; Bhanage, B. M. Tetrahedron Lett. 2008, 49,
2221–2224; (d) Sawant, D. N.; Wagh, Y. S.; Bhatte, K. D.;
Bhanage, B. M. J. Org. Chem. 2011, 76, 5489–5494; (e) Ju, J.;
Jeong, M.; Moon, J.; Jung, H. M.; Lee, S. Org. Lett. 2007, 9,
4615–4618; (f) Jo, Y.; Ju, J.; Choe, J.; Song, K. H.; Lee, S. J. Org.
Chem. 2009, 74, 6358–6361.
N,N-Dimethyl-2-nitrobenzamide
Yellow oil. 1H NMR (300 MHz, CDCl3) δ: 8.20 (d, J = 6.0 Hz,
1H), 7.73 (t, J = 7.5 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.41 (d, J =
6 Hz, 1H), 3.17 (s, 3H), 2.85 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ: 167.9, 145.1, 134.6, 133.3, 129.7, 128.1, 124.7, 38.2, 34.9.
HRMS ESI (m/z): [M+Na]+ calcd for C9H10N2NaO3, 217.0584;
found, 217.0593.
11. He, T.; Li, H.; Li, P.; Wang, L. Chem. Commun. 2011, 47, 8946–
8948.
12. Kumagai, T.; Kawase, T. Tetrahedron 2010, 66, 8968–8973.
13. (a) Liu, Z.; Zhang, J.; Chen, S.; Shi, E.; Xu, Y.; Wan, X. Angew.
Chem. Int. Ed. 2012, 51, 3231–3235; (b) Xu, K.; Hu, Y.; Zhang,
S.; Zha, Z.; Wang, Z. Chem. Eur. J. 2012, 18, 9793–9797.
14. During our submission, the similar methodology was reported for
the synthesis of amides, please see: Kumar, P. S.; Kumar, G. S.;
Kumar, R. A.; Reddy, N. V.; Reddy, K. R. Eur. J. Org. Chem.
2013, 1218–1222.
15. Narasimhan, B.; Belsare, D.; Pharande, D.; Mourya, V.; Dhake, A.
Eur. J. Med. Chem. 2004, 39, 827–834.
16. Gephart, R. T.; McMullin, C. L.; Sapiezynski, N. G.; Jang, E. S.;
Aguila, M. J. B.; Cundari, T. R.; Warren, T. H. J. Am. Chem. Soc.
2012, 134, 17350–17353.
N,N-Diethylcinnamamide
White solid, m.p. 67-69 oC. 1H NMR (400 MHz, CDCl3) δ: 7.71
(d, J = 16.0 Hz, 1H), 7.54-7.51 (m, 2H), 7.39-7.33 (m, 3H), 6.83
(d, J = 16.0 Hz, 1H), 3.52-3.45 (m, 4H), 1.26 (t, J = 8.0 Hz, 3H),
1.19 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 165.9,
142.5, 135.7, 129.6, 128.9, 127.9, 118.0, 42.5, 41.3, 15.3, 13.4.
HRMS ESI (m/z): [M+H]+ calcd for C13H18NO, 204.1383; found,
204.1379.
17. Rout, S. K.; Guin, S.; Ghara, K. K.; Banerjee, A.; Patel, B. K.
Org. Lett. 2012, 14, 3982–3985.
18. Rothenberg, G.; Feldberg, L.; Wiener, H.; Sasson, Y. J. Chem.
Soc. Perkin Trans. 2 1998, 2, 2429–2434.
19. Li, Y.; Xie, Y.; Zhang, R.; Jin, K.; Wang, X.; Duan, C. J. Org.
Chem. 2011, 76, 5444–5449.
20. Wei, W.; Zhang, C.; Xu, Y.; Wan, X. Chem. Commun. 2011, 47,
10827–10829.
(E)-tert-Butyl 3-phenylprop-2-eneperoxoate (I)
1H NMR (400 MHz, CDCl3) δ: 7.75 (d, J = 16.0 Hz, 1H), 7.53 (t,
J = 4.0 Hz, 2H), 7.40 (t, J = 3.0 Hz, 3H), 6.41 (d, J = 16.0 Hz,
1H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 165.5, 146.3,
134.2, 130.9, 129.2, 128.4, 113.4, 83.9, 26.4. MS ESI (m/z):
[M+Na]+ calcd for C13H16NaO3, 243.1; found, 243.1.
Acknowledgments
We are grateful to the grants from International S&T
Cooperation Program of Jiangsu Province (BZ2010048), the
Scientific Research Foundation for the Returned Overseas
Chinese Scholars, State Education Ministry, the Priority
Academic Program Development of Jiangsu Higher Education
Institutions, and the Key Laboratory of Organic Synthesis of
Jiangsu Province.
References and notes
1. (a) Hirsch-Weil, D.; Abboud, K. A.; Hong, S. Chem. Commun.
2010, 46, 7525–7527; (b) Nemoto, T.; Kakei, H.; Gnanadesikan,
V.; Tosaki, S.Y.; Ohshima, T.; Shibasaki, M. J. Am. Chem. Soc.
2002, 124, 14544–14545; (c) Tosaki, S.-Y.; Tsuji, R.; Ohshima, T.;
Shibasaki, M. J. Am. Chem. Soc. 2005, 127, 2147–2155; (d)
Cheung, C. W.; Buchwald, S. L. J. Org. Chem. 2012, 77, 7526–
7537; (e) Lesniak, S.; Nazarski, R. B.; Pasternak, B. Tetrahedron
2009, 65, 6364–6369.

ACCEPTED MANUSCRIPT
Supporting Information
Copper-Catalyzed Synthesis of α, β-Unsaturated Acylamides via
Direct Amidation from Cinnamic Acids and N-Substituted
Formamides
Hong Yan, Hailong Yang, Linhua Lu, Defu Liu, Guangwei Rong and Jincheng Mao*
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical
Engineering and Materials Science
Soochow University, Suzhou 215123, P. R. China
Fax: (+86)512-6588-0403
E-mail: jcmao@suda.edu.cn
-S1-

ACCEPTED MANUSCRIPT
General Information:
All reactions were carried out under an argon atmosphere condition. Cupric sulfate was
purchased from Alfa. Various cinnamic acids and N-substituted formamides were purchased from
Aldrich, Acros or Alfa. Column chromatography was generally performed on silica gel (100-200
mesh) and reactions were monitored by thin layer chromatography (TLC) using UV light (254
1
nm) to visualize the course of the reactions. The H (300 MHz or 400 MHz) and 13C NMR (75
MHz or 100 MHz) data were recorded on Varian 300 M or 400 M spectrometers using CDCl3 as
1
solvent. The chemical shifts (δ) are reported in ppm and coupling constants (J) in Hz. H NMR
spectra was recorded with tetramethylsilane (δ = 0.00 ppm) as internal reference; 13C NMR
spectra was recorded with CDCl3 (δ = 77.000 ppm) or DMSO-d6 (δ = 39.500 ppm) as internal
reference. ESI-MS and HRMS were performed by the State-authorized Analytical Center in
Soochow University.
General procedure for copper-catalyzed direct amidation between cinnamic acid and
N-substituted formamide: CuSO4 (0.06 mmol) and cinnamic acid (0.3 mmol) were added to a
Schlenk tube equipped with a magnetic stir bar under argon atmosphere. Then N-substituted
formamide (2.0 mL) and DTBP (di-tert-butyl peroxide, 0.6 mmol) were added under Ar. The
resulting reaction mixture was kept stirring until TLC monitoring indicated the complete
disappearance of the starting material. At the end of the reaction, the reaction mixture was cooled
to room temperature and was diluted with ethyl acetate and water was added. The combined
organic phase was dried over anhydrous Na2SO4. After removal of the solvent, the residue was
subjected to column chromatography on silica gel using ethyl acetate and petroleum ether
mixtures to afford the corresponding product.
-S2-

ACCEPTED MANUSCRIPT
Characterization of the corresponding products:
(E)-N,N-Dimethylcinnamamide (3aa)
1H NMR (300 MHz, CDCl3) δ: 7.68 (d, J = 15.0 Hz, 1H), 7.52 (s, 2H), 7.35 (s, 2H), 6.90 (d, J =
15.0 Hz, 1H), 3.17 (s,3H), 3.07 (s,3H); 13C NMR (75 MHz, CDCl3) δ: 166.7, 142.3, 135.3, 129.5,
128.8, 127.8, 117.4, 37.4, 35.9. MS ESI (m/z): [M+H]+ calcd for C11H14NO, 176.1; found, 176.1.
(E)-3-(4-Chlorophenyl)-N,N-dimethylacrylamide (3ba)
1H NMR (400 MHz, CDCl3) δ: 7.61 (d, J = 16.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0
Hz, 2H), 6.86 (d, J = 16.0 Hz, 1H), 3.16 (s, 3H), 3.06 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.3,
140.9, 135.2, 133.7, 128.9, 128.9, 117.9, 37.3, 35.9. HRMS ESI (m/z): [M+Na]+ calcd for
C11H12ClNNaO, 232.0500; found, 232.0500.
(E)-3-(4-Fluorophenyl)-N,N-dimethylacrylamide (3ca)
1H NMR (300 MHz, CDCl3) δ: 7.64 (d, J = 15.0 Hz, 1H), 7.54-7.49 (m, 2H), 7.09-7.02 (m, 2H),
6.83 (d, J = 15.0 Hz, 1H), 3.17 (s, 3H), 3.07 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.4, 163.3
(d, J = 201.8 Hz), 140.9, 131.4 (d, J = 2.3 Hz), 129.4 (d, J = 8.3 Hz), 117.0, 115.7 (d, J = 21.8 Hz),
37.3, 35.8. HRMS ESI (m/z): [M+H]+ calcd for C11H13FNO, 194.0976; found, 194.0987.
(E)-N,N-Dimethyl-3-(4-(trifluoromethyl)phenyl)acrylamide (3da)
1H NMR (400 MHz, CDCl3) δ: 7.67 (d, J = 16.0 Hz, 1H), 7.62 (s, 4H), 6.97 (d, J = 16.0 Hz, 1H),
3.19 (s, 3H), 3.08 (s, 3H);13C NMR (75 MHz, CDCl3) δ: 166.0, 139.6 (d, J = 136.5 Hz), 131.0 (d,
J = 32.3 Hz), 127.9, 125.7 (q, J = 3.5 Hz), 122.1, 119.9, 37.4, 35.9. HRMS ESI (m/z): [M+Na]+
calcd for C12H12F3NNaO, 266.0763; found, 266.0766.
(E)-3-(4-Isopropylphenyl)-N,N-dimethylacrylamide (3ea)
-S3-

ACCEPTED MANUSCRIPT
1H NMR (400 MHz, CDCl3) δ: 7.65 (d, J = 16.0 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0
Hz, 2H), 6.85 (d, J = 16.0 Hz, 1H), 3.16 (s, 3H), 3.06 (s, 3H), 2.95-2.86 (m, 1H), 1.25 (d, J = 8.0
Hz, 6H); 13C NMR (75 MHz, CDCl3) δ: 166.8, 150.6, 142.2, 132.9, 127.7, 126.8, 116.3, 37.3, 35.8,
33.9, 23.7. HRMS ESI (m/z): [M+Na]+ calcd for C14H19NNaO, 240.1359; found, 240.1364.
(E)-N,N-Dimethyl-3-(p-tolyl)acrylamide (3fa)
1H NMR (400 MHz, CDCl3) δ: 7.64 (d, J = 16.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0
Hz, 2H), 6.84 (d, J = 16.0 Hz, 1H), 3.15 (s, 3H), 3.05 (s, 3H), 2.36 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ: 166.9, 142.3, 139.8, 132.6, 129.5, 127.7, 116.3, 37.4, 35.9, 21.4. HRMS ESI (m/z):
[M+Na]+ calcd for C12H15NNaO, 212.1046; found, 212.1053.
(E)-N,N-Dimethyl-3-(m-tolyl)acrylamide (3ga)
1H NMR (300 MHz, CDCl3) δ: 7.65 (d, J = 15.0 Hz, 1H), 7.33-7.23 (m, 3H), 7.17 (s, 1H), 6.88 (d,
J = 15.0 Hz, 1H), 3.17 (s, 3H), 3.06 (s, 3H), 2.36 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.6,
142.3, 138.2, 135.1, 130.2, 128.5, 128.2, 124.8, 117.0, 37.2, 35.7, 21.2. HRMS ESI (m/z):
[M+Na]+ calcd for C12H15NNaO, 212.1046; found, 212.1054.
(E)-3-(4-Methoxyphenyl)-N,N-dimethylacrylamide（3ha）
1H NMR (300 MHz, CDCl3) δ: 7.64 (d, J = 15.0 Hz, 1H), 7.48 (d, J = 9.0 Hz, 2H), 6.89 (d, J = 9.0
Hz, 2H), 6.76 (d, J = 15.0 Hz, 1H), 3.81 (s, 3H), 3.15 (s, 3H), 3.05 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ: 166.9, 160.7, 141.9, 129.2, 127.9, 114.8, 114.1, 55.2, 37.3, 35.8. HRMS ESI (m/z):
[M+H]+ calcd for C12H16NO2, 206.1176; found, 206.1175.
(E)-3-(2-Methoxyphenyl)-N,N-dimethylacrylamide（3ia）
1H NMR (300 MHz, CDCl3) δ: 7.92 (d, J = 15.0 Hz, 1H), 7.49 (d, J = 6.0 Hz, 1H), 7.30-7.27 (m,
1H), 7.02-6.89 (m, 3H), 3.86 (s, 3H), 3.15 (s, 3H), 3.05 (s, 3H); 13C NMR (75 MHz, CDCl3) δ:
167.1, 157.9, 137.6, 130.4, 128.7, 124.1, 120.4, 118.2, 110.9, 55.2, 37.2, 35.6. HRMS ESI (m/z):
[M+Na]+ calcd for C12H15NNaO2, 228.0995; found, 228.1003.
-S4-

ACCEPTED MANUSCRIPT
(E)-3-(3-Methoxyphenyl)-N,N-dimethylacrylamide（3ja）
1H NMR (400 MHz, CDCl3) δ: 7.63 (d, J = 16.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 4.0
Hz, 1H), 7.04 (s, 1H), 6.91-6.85 (m, 2H), 3.83 (s, 3H), 3.16 (s, 3H), 3.06 (s, 3H); 13C NMR (75
MHz, CDCl3) δ: 166.6, 159.8, 142.2, 136.7, 129.7, 120.3, 117.7, 115.0, 113.1, 55.3, 37.4, 35.9.
HRMS ESI (m/z): [M+H]+ calcd for C12H16NO2, 206.1176; found, 206.1179.
(E)-3-(3,4-Dimethoxyphenyl)-N,N-dimethylacrylamide (3ka)
1H NMR (300 MHz, CDCl3) δ: 7.61 (d, J = 15.0 Hz, 1H), 7.11 (d, J = 6.0 Hz, 1H), 7.03 (s, 1H),
6.85 (d, J = 6.0 Hz, 1H), 6.75 (d, J = 15.0 Hz, 1H), 3.91 (d, J = 3.0 Hz, 6H), 3.17 (s, 3H), 3.06 (s,
3H); 13C NMR (75 MHz, CDCl3) δ: 166.9, 150.4, 149.0, 142.3, 128.3, 121.7, 115.1, 111.1, 109.9,
55.9, 37.4, 35.9. HRMS ESI (m/z): [M+H]+ calcd for C13H18NO3, 236.1281; found, 236.1285.
(E)-N,N-Dimethyl-3-(3,4,5-trimethoxyphenyl)acrylamide (3la)
1H NMR (300 MHz, CDCl3) δ: 7.50 (d, J = 15.0 Hz, 1H), 6.70 (d, J = 18.0 Hz, 3H), 3.80 (d, J =
6.0 Hz, 9H), 3.10 (s, 3H), 2.98 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 166.4, 153.2, 142.2, 139.3,
130.7, 116.5, 104.8, 60.7, 56.0, 37.3, 35.8. HRMS ESI (m/z): [M+H]+ calcd for C14H20NO4,
266.1387; found, 266.1395.
O
N
O2N
N,N-Dimethyl-3-(4-nitrophenyl)acrylamide (3ma)
(E)-N,N-Dimethyl-3-(4-nitrophenyl)acrylamide: 1H NMR (400 MHz, CDCl3) δ: 8.23 (d, J = 8.0
Hz, 2H), 7.71-7.66 (m, 3H), 7.04 (d, J = 16.0 Hz, 1H), 3.21 (s, 3H), 3.10 (s, 3H);
1
(Z)-N,N-Dimethyl-3-(4-nitrophenyl)acrylamide: H NMR (400 MHz, CDCl3) δ: 8.18 (d, J = 8.0
Hz, 2H), 7.55 (d, J = 12.0 Hz, 2H), 6.72 (d, J = 12.0 Hz, 1H), 6.31 (d, J = 12.0 Hz, 1H), 3.01 (s, 3H),
2.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 165.6, 148.0, 141.5, 139.5, 128.3, 124.0, 121.7, 37.4,
36.0. HRMS ESI (m/z): [M+H]+ calcd for C11H13N2O3, 221.0921; found, 221.092.
-S5-

ACCEPTED MANUSCRIPT
(E)-N,N-Dimethyl-3-(naphthalen-1-yl)acrylamide (3na)
1H NMR (400 MHz, CDCl3) δ: 8.49 (d, J = 16.0 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.0
Hz, 2H), 7.70 (d, J = 8.0 Hz, 1H), 7.57-7.50 (m, 2H), 7.49-7.44 (m, 1H), 6.94 (d, J = 16.0 Hz, 1H),
3.18 (s, 3H), 3.10 (s, 3H);13C NMR (75 MHz, CDCl3) δ: 166.6, 139.7, 133.6, 133.1, 131.5, 129.7,
128.5, 126.6, 126.1, 125.4, 124.5, 123.8, 120.5, 37.5, 36.0. HRMS ESI (m/z): [M+Na]+ calcd for
C15H15NNaO, 248.1046; found, 248.1046.
(E)-3-(Furan-2-yl)-N,N-dimethylacrylamide (3oa)
1H NMR (300 MHz, CDCl3) δ: 7.47-7.36 (m, 2H), 6.81(d, J = 15.0 Hz, 1H), 6.55 (s, 1H), 6.45 (s,
1H), 3.16 (s, 3H), 3.06(s, 3H);13C NMR (75 MHz, CDCl3) δ: 166.5, 151.6, 143.7, 129.1, 114.8,
113.7, 112.1, 37.3, 35.9. HRMS ESI (m/z): [M+Na]+ calcd for C9H11NNaO2, 188.0687; found,
188.0694.
(E)-N,N-Dimethyl-3-(thiophen-2-yl)acrylamide (3pa)
1H NMR (400 MHz, CDCl3) δ: 7.79 (d, J = 16.0 Hz, 1H), 7.31 (d, J = 4.0 Hz, 1H), 7.21 (d, J = 4.0
Hz, 1H), 7.04-7.02 (m, 1H), 6.69 (d, J = 16.0 Hz, 1H), 3.14 (s, 3H), 3.05 (s, 3H); 13C NMR (75
MHz, CDCl3) δ: 166.2, 140.4, 135.0, 130.0, 127.8, 127.0, 116.0, 37.3, 35.8. HRMS ESI (m/z):
[M+H]+ calcd for C9H12NOS, 182.0634; found, 182.0639.
(E)-N,N-Dimethyl-3-(pyridin-3-yl)acrylamide (3qa)
1H NMR (400 MHz, CDCl3) δ: 8.76 (d, J = 1.6.0 Hz, 1H), 8.58-8.56 (m, 1H), 7.84-7.81 (m, 1H),
7.65 (d, J = 16.0 Hz, 1H), 7.33-7.30 (m, 1H), 6.98 (d, J = 16.0 Hz, 1H), 3.19 (s, 3H), 3.08 (s, 3H);
13C NMR (75 MHz, CDCl3) δ: 165.9, 150.1, 149.1, 138.5, 134.2, 131.0, 123.5, 119.5, 37.3, 35.9.
HRMS ESI (m/z): [M+H]+ calcd for C10H13N2O, 177.1022; found, 177.1014.
-S6-

ACCEPTED MANUSCRIPT
(E)-N,N,2-Trimethyl-3-phenylacrylamide (3ra)
1H NMR (400 MHz, CDCl3) δ: 7.40-7.33 (m, 4H), 7.30-7.28 (m, 1H), 6.55 (s, 1H), 3.07 (s, 6H),
2.12 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 173.6, 136.0, 133.3, 129.6, 129.0, 128.3, 127.3, 38.7,
34.9, 15.9. HRMS ESI (m/z): [M+H]+ calcd for C12H16NO, 190.1226; found, 190.1231.
(E)-N,N-Diethyl-3-(4-isopropylphenyl)acrylamide (3eb)
1H NMR (400 MHz, CDCl3) δ: 7.69 (d, J = 16.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0
Hz, 2H), 6.78 (d, J = 16.0 Hz, 1H), 3.52-3.44 (m, 4H), 2.97- 2.86 (m, 1H), 1.25 (d, J = 8.0 Hz,
9H), 1.19 (t, J = 6.0 Hz, 3H ); 13C NMR (75 MHz, CDCl3) δ: 165.8, 150.5, 142.2, 133.0, 127.7,
126.8, 116.7, 42.2, 41.0, 33.9, 23.7, 15.0, 13.2. HRMS ESI (m/z): [M+H]+ calcd for C16H24NO,
246.1852; found, 246.1854.
(E)-N,N-Dibutyl-3-(4-isopropylphenyl)acrylamide (3ec)
1H NMR (400 MHz, CDCl3) δ: 7.68 (d, J = 16.0 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0
Hz, 2H), 6.79 (d, J = 16.0 Hz, 1H), 3.44-3.37 (m, 4H), 2.97-2.87 (m, 1H), 1.66-1.54 (m, 4H),
1.42-1.31 (m, 4H), 1.26 (d, J = 8.0 Hz, 6H), 0.99-0.93 (m, 6H); 13C NMR (75 MHz, CDCl3) δ:
166.2, 150.5, 142.1, 133.2, 127.8, 126.8, 116.8, 47.9, 46.7, 34.0, 31.9, 30.1, 23.8, 20.3, 20.1, 13.9,
13.8. HRMS ESI (m/z): [M+H]+ calcd for C20H32NO, 302.2478; found, 302.2468.
(E)-3-(4-Isopropylphenyl)-1-(pyrrolidin-1-yl)prop-2-en-1-one (3ed)
1H NMR (400 MHz, CDCl3) δ: 7.68 (d, J = 16.0 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0
Hz, 2H), 6.69 (d, J = 16.0 Hz, 1H), 3.64-3.57 (m, 4H), 2.97-2.86 (m, 1H), 2.03-1.96 (m, 2H),
1.92-1.85 (m, 2H), 1.25 (d, J = 8.0 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ: 164.8, 150.6, 141.6,
132.8, 127.8, 126.7, 117.7, 46.5, 45.9, 33.9, 26.0, 24.2, 23.7. HRMS ESI (m/z): [M+H]+ calcd for
C16H22NO, 244.1696; found, 244.1695.
-S7-

ACCEPTED MANUSCRIPT
(E)-3-(4-isopropylphenyl)-1-(piperidin-1-yl)prop-2-en-1-one (3ee)
1H NMR (400 MHz, CDCl3) δ: 7.62 (d, J = 16.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0
Hz, 2H), 6.85 (d, J = 16.0 Hz, 1H), 3.62 (d, J = 28.0 Hz, 4H), 2.96-2.86 (m, 1H), 1.69-1.66 (m, 2H),
1.61-1.57 (m, 4H), 1.25 (d, J = 8.0 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ: 165.51, 150.51, 142.14,
133.06, 127.69, 126.78, 116.63, 46.96, 43.29, 33.95, 26.70, 25.56, 24.60, 23.77. HRMS ESI (m/z):
[M+H]+ calcd for C17H24NO, 258.1852; found, 258.1841.
(E)-3-(4-Isopropylphenyl)-1-morpholinoprop-2-en-1-one (3ef)
1H NMR (400 MHz, CDCl3) δ: 7.69 (d, J = 16.0 Hz, 1H), 7.46 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0
Hz, 2H), 6.80 (d, J = 16.0 Hz, 1H), 3.70 (d, J = 16.0 Hz, 8H), 2.97-2.87 (m, 1H), 1.26 (d, J = 8.0
Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 165.7, 150.9, 143.2, 132.7, 127.8, 126.9, 115.4, 66.8,
46.3, 46.1, 42.4, 34.0, 23.7. HRMS ESI (m/z): [M+H]+ calcd for C16H22NO2, 260.1645; found,
260.1646.
(E)-3-(4-Isopropylphenyl)acrylamide (3eg)
1H NMR (400 MHz, DMSO-d6) δ: 7.51 (s, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 16.0 Hz, 1H),
7.27 (d, J = 8.0 Hz, 2H), 7.06 (s, 1H), 6.56 (d, J = 16.0 Hz, 1H), 2.94-2.84 (m, 1H), 1.19(d, J = 8.0
Hz, 6H); 13C NMR (100 MHz, DMSO-d6) δ: 166.9, 150.1, 139.3, 132.6, 127.7, 126.9, 121.3, 33.4,
23.7. HRMS ESI (m/z): [M+Na]+ calcd for C12H15NNaO, 212.1046; found, 212.1042.
(E)-3-(4-Isopropylphenyl)-N-methylacrylamide (3eh)
1H NMR (400 MHz, CDCl3) δ: 7.61 (d, J = 16.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0
Hz, 2H), 6.38 (d, J = 16.0 Hz, 1H), 5.90 (s, 1H), 2.94-2.87 (m, 4H), 1.24 (d, J = 8.0 Hz, 6H);13C
-S8-

ACCEPTED MANUSCRIPT
NMR (100 MHz, CDCl3) δ: 167.2, 151.0, 140.9, 132.7, 128.0, 127.1, 119.8, 34.2, 26.7, 24.0.
HRMS ESI (m/z): [M+H]+ calcd for C13H18NO, 204.1383; found, 204.1384.
N,N-Dimethyl-2-nitrobenzamide
1H NMR (300 MHz, CDCl3) δ: 8.20 (d, J = 6.0 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.58 (t, J = 7.5
Hz, 1H), 7.41 (d, J = 6 Hz, 1H), 3.17 (s, 3H), 2.85 (s, 3H); 13C NMR (75 MHz, CDCl3) δ: 167.9,
145.1, 134.6, 133.3, 129.7, 128.1, 124.7, 38.2, 34.9. HRMS ESI (m/z): [M+Na]+ calcd for
C9H10N2NaO3, 217.0584; found, 217.0593.
N,N-diethylcinnamamide
1H NMR (400 MHz, CDCl3) δ: 7.71 (d, J = 16.0 Hz, 1H), 7.54-7.51 (m, 2H), 7.39-7.33 (m, 3H),
6.83 (d, J = 16.0 Hz, 1H), 3.52-3.45 (m, 4H), 1.26 (t, J = 8.0 Hz, 3H), 1.19 (t, J = 8.0 Hz, 3H);13C
NMR (100 MHz, CDCl3) δ: 165.9, 142.5, 135.7, 129.6, 128.9, 127.9, 118.0, 42.5, 41.3, 15.3, 13.4.
HRMS ESI (m/z): [M+H]+ calcd for C13H18NO, 204.1383; found, 204.1379.
(E)-tert-Butyl 3-phenylprop-2-eneperoxoate (I)
1H NMR (400 MHz, CDCl3) δ: 7.75 (d, J = 16.0 Hz, 1H), 7.53 (t, J = 4.0 Hz, 2H), 7.40 (t, J = 3.0
Hz, 3H), 6.41 (d, J = 16.0 Hz, 1H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 165.5, 146.3,
134.2, 130.9, 129.2, 128.4, 113.4, 83.9, 26.4. MS ESI (m/z): [M+Na]+ calcd for C13H16NaO3,
243.1; found, 243.1.
-S9-

ACCEPTED MANUSCRIPT
Copy of HRMS and NMR Spectra for desired products:
-S10-

ACCEPTED MANUSCRIPT
-S11-

ACCEPTED MANUSCRIPT
-S12-

ACCEPTED MANUSCRIPT
-S13-

ACCEPTED MANUSCRIPT
-S14-

ACCEPTED MANUSCRIPT
-S15-

ACCEPTED MANUSCRIPT
-S16-

ACCEPTED MANUSCRIPT
-S17-

ACCEPTED MANUSCRIPT
-S18-

ACCEPTED MANUSCRIPT
-S19-

ACCEPTED MANUSCRIPT
-S20-

ACCEPTED MANUSCRIPT
-S21-

ACCEPTED MANUSCRIPT
-S22-