Synthesis of 1-acetoxy-2-aminoakenes via condensation of amino with carbonyl and C=C acetoxylation

Article abstract of DOI:10.1002/hc.21016

1-Acetoxy-2-aminoakenes were synthesized through an effective synthetic route using acid as the catalyst and (diacetoxyiodo)benzene as the oxidant, which is also a novel strategy for the formation of two C-heteroatom bonds in the same reaction. In addition, it is a practical protocol with high regioselectivity, atom efficiency, and good substrate scope.

Full text of DOI:10.1002/hc.21016

Heteroatom Chemistry
Volume 23, Number 3, 2012
Synthesis of 1-Acetoxy-2-aminoakenes via
–
Condensation of Amino with Carbonyl and C C
–
Acetoxylation
Wei-Bing Liu, Cui Chen, and Qing Zhang
School of Chemistry and Life Science, Guangdong University of Petrochemical Technology,
Maoming 525000, People’s Republic of China
Received 28 December 2011; revised 17 February 2012
catalysts, as well as frequently require multistep syn-
ABSTRACT: 1-Acetoxy-2-aminoakenes were synthe-
theses or extreme reaction conditions. In connection
sized through an effective synthetic route using acid
with our interest in polyvalent iodine reagents [16–
as the catalyst and (diacetoxyiodo)benzene as the oxi-
18], they have been extensively used in modern or-
dant, which is also a novel strategy for the formation of
ganic synthesis in oxidative coupling to form novel
two C-heteroatom bonds in the same reaction. In addi-
C C, C O, and C N bonds due to their low toxicity,
tion, it is a practical protocol with high regioselectivity,
easy handling, and high reactivity [19–25]. Recently,
ꢀ
C
atom efficiency, and good substrate scope. 2012 Wi-
we observed a notable outcome, including conden-
ley Periodicals, Inc. Heteroatom Chem 23:290–294, 2012;
sation of primary amines with carbonyl and subse-
View this article online at wileyonlinelibrary.com. DOI
quent diacetoxyiodobenzene (DIB), a mediated C H
10.1002/hc.21016
bond acetoxylation, representing an example of con-
structing new 1-acetoxy-2-aminoakenes (Scheme 1).
INTRODUCTION
RESULTS AND DISCUSSION
Alkenes are one of the most important classes of
To achieve the suitable conditions of the above trans-
organic compounds as they are not only a key
formation, a series of experiments were carried out
structural attribute of many bioactive natural prod-
(Table 1). As shown in Table 1, this reaction was
ucts [1,2], but also an useful and versatile build-
sensitive to the solvent medium (Table 1, entries
ing block that can be used as starting materials
6–9). Among the various solvents examined, the best
for many classes of compounds in organic synthe-
result was obtained in dichloromethane (Table 1,
sis [3–7]. Not surprisingly, many synthetic meth-
entries 1–5). The reaction time as well as temper-
ods have been reported for preparation of general
ature had an obvious effect on this reaction. The re-
alkenes [8–14]. Nevertheless, there are no simple,
sults showed that the desirable reaction temperature
general procedures available for the preparation of
was 0◦ C, and the preferable reaction time was 12 h
1,2-diheteroatom-substituted alkenes [15]; some of
(Table 1, entries 6–9). The structure of products was
them suffer from poor stereoselectivity, low yields,
confirmed by 1H NMR, 13C NMR, and NOE. The con-
figuration of the 1-acetoxy-2-aminoakenes was fur-
or the use of expensive reagents or transition metal-
ther confirmed by NOE studies on compound 6.
Correspondenceto:Wei-Bing Liu; e-mail: lwb409@yahoo.com.cn.
Contract grant sponsor: Guangdong University of Petrochemi-
cal Technology of China.
1.89
H
N
2.34
2.07
O
Supporting Information is available in the online issue at
wileyonlinelibrary.com.
O
2.27
c
ꢀ
O
2012 Wiley Periodicals, Inc.
290

Synthesis of 1-Acetoxy-2-aminoakenes via Condensation of Amino with Carbonyl and C C Acetoxylation 291
R2
followed by the iodine(III) electrophile attack on
nitrogen [17, 18] or C C bond [28] to give inter-
mediate 17 or 19 by losing one molecule of acetic
acid. The subsequent N I bond or C I bond cleav-
age along with nucleophilic attack of acetic acid on
the C C bond or C C bond affords imine 18 by elim-
inating 1 equiv of iodobenzene and 1 equiv of acetic
acid. Finally, the desired product 3 is produced af-
ter isomerization of 18 to a more stable conjugated
enamine form.
R3 NH
R1
O
O
O
Acid, DIB
R3NH2
+
R1
R2
OAc
SCHEME 1 Synthesis of 1,2-diheteroatom-substituted (E)-
alkenes.
TABLE 1 Optimization of Reaction Conditionsa
H
O
O
N
Acid, DIB
Solvent
+
NH2
AcO
3
O
2a
1a
CONCLUSIONS
Temperature Reactional Yield
(◦C)
Time (h)
(%)b
In summary, we have demonstrated here an effec-
tive synthetic route for the synthesis of 1-acetoxy-2-
aminoakenes with high stereoselectivity. These com-
pounds are attractive substrates for use in inverse
electron demand Diels–Alder, Paterno–Bu¨chi, and
enamine reactions, among others. Further investi-
gations into the scope of this catalytic/oxidative pro-
cedure and applications to synthesis are currently
under way in this laboratory.
Entry Solvent
1
2
Toluene
1,2-dichloroethane
(DCE)
CH2Cl2
Dioxane
Acetonitrile
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0
0
12
12
26
80
3
4
5
6
7
8
9
0
0
0
r. t.
−10
0
12
12
12
12
12
8
83
73
42
63
78
71
84
0
24
aThe reaction was carried out using 0.25 mmol of 1a, 0.25 mmol of
2a, 0.20 equiv. of acetic acid, 1.2 equiv. of DIB, 2.0 mL of solvent.
bGC yield.
EXPERIMENTAL
General Procedure
All the reactions were carried out at 0◦C in a Schlenk
tube equipped with a magnetic stir bar. Solvents and
all reagents were used as received. H NMR spectra
A variety of 1,3-dicarbonyl compounds and
amines were subjected to the above optimal reac-
tion conditions (Table 1, entry 3) to probe the reac-
tion scope and generality (Scheme 2). As revealed
in Scheme 2, amines, regardless of whether with
aliphatic-substituted groups or aromatic-substituted
groups, appear quite tolerant for this protocol and
make this transformation proceed smoothly with
high stereoselectivity and afford the desired product
in moderate to excellent yields. For example, the re-
actions of acetylacetone (1a) with n-butylamine (2a)
or aniline (2c) both led to 1-acetoxy-2-aminoakenes
in good isolated yields (3, 5). However, the sub-
stituents on the 1,3-dicarbonyl compounds have
an obvious effect on this reaction. As revealed in
Scheme 2, when R1 = R2, this transformation would
proceed smoothly (3–6); whereas when R1 = R2, the
reaction would lead to inferior results. For example,
when R1 = CH3, R2 = Oet, or R2 = benzene, the re-
actions would lead to inferior yields (7: 72%; 8: 67%;
9: 60%; 10: 65%; 11: 66% and 12: 58%).
1
were recorded in CDCl3 at 400 MHz, and 13C NMR
spectra were recorded in CDCl3 at 100 MHz. GC–
MS was obtained using electron ionization (EI). TLC
was performed using commercially prepared 100–
400 mesh silica gel plates (GF254), and visualiza-
tion was effected at 254 nm. All the other chemicals
were purchased from Aldrich (Guangzhou, Guang-
dong Province, China).
Typical Procedure for the Synthesis of (E)-2-
(Butylamino)-4-oxopent-2-en-3-yl Acetate 3
A mixture of DIB (386 mg, 1.2 mmol), AcOH (12
mg, 0.2 mmol), dichloromethane (2 mL), acetylace-
tone (1a) (100 mg, 1.0 mmol), and n-butylamine
(2a) (73 mg, 1 mmol) was added successively
in a Schlenk tube. After stirring for 12 h at
0◦C, the solution was directly subjected to isola-
tion by PTLC (prepared thin-layer chromatography)
(GF254) eluted with a 10:3 petroleum ether/ethyl ac-
etate mixture, which furnished (E)-2-(butylamino)-
4-oxopent-2-en-3-yl acetate 3 (134.9 mg, 78%) as a
dark brown viscous oil.
The plausible mechanism for this transfor-
mation, exemplified by the formation of (E)-2-
(butylamino)-4-oxopent-2-en-3-yl acetate 3, is sum-
marized in Scheme 3. This reaction is initiated with
the formation of enamine 16 [26, 27], which was
Heteroatom Chemistry DOI 10.1002/hc

292 Liu, Chen, and Zhang
H
N
DIB (1.2 equiv.)
R3
R2
R1
O
O
AcOH (0.2 equiv.)
R3 NH2
+
R1
R2
0°C , 12 h
CH2Cl2 (2 mL)
AcO
O
1
2
H
N
H
N
H
N
H
N
AcO
AcO
AcO
O
AcO
O
O
O
3 78%
6 86%
4 83%
5 80%
H
N
H
H
N
N
OEt
OEt
AcO
AcO
AcO
O
O
O
9 60%
8 67%
7 72%
H
N
H
N
H
N
AcO
AcO
AcO
O
O
O
12 58%
11 66%
10 65%
SCHEME 2 Synthesis of 1, 2-diheteroatom-substituted (E)-alkenes from 1,3-dicarbonyl compounds and amines. The yields
of isolated products are listed.
(E)-2-(Butylamino)-4-oxopent-2-en-3-yl acetate
(3). Dark brown viscous oil, IR νmax (KBr): 3382,
1752, 1688, 1433, 1208, 1027, 853, 707, 666,
20.4, 12.7; GC-MS m/z (% rel inten.): 246.98 (M+,
12.98), 90.78 (100); Anal. Calcd for C14H17NO3: C,
68.00; H, 6.93; N, 5.66; Found: C, 68.25; H, 6.81; N,
5.82.
1
cm−1; H NMR (400 MHz, CDCl3): δ 10.69 (s, 1H),
3.23–3.18 (t, 2H, J = 8.0 Hz), 2.20 (s, 3H), 1.95 (s,
3H), 1.84 (s, 3H), 1.57–1.54 (m, 2H), 1.41–1.35 (m,
2H), 0.93–0.89 (t, 3H, J = 8.0 Hz); 13C NMR (100
MHz, CDCl3): δ 189.5, 170.9, 156.6, 123.3, 42.9, 31.9,
24.9, 20.5, 19.9, 13.7, 12.7; GC-MS m/z (% rel inten.):
213.10 (M+, 38.23), 170.99 (100); Anal. Calcd for
C11H19NO3: C, 61.95; H, 8.98; N, 6.57; Found: C,
61.82; H, 8.88; N, 6.72.
(E)-4-Oxo-2-(phenylamino)pent-2-en-3-yl acetate
(5). Pale yellow crystal, mp: 102–104◦C; IR νmax
(KBr): 3462, 3310, 1732, 1666, 1610, 1500, 1458,
1220, 1025, 707, 670, cm−1; 1H NMR (400 MHz,
CDCl3): δ 12.17 (s, 1H), 7.46–7.42 (m, 1H), 7.35–
7.33 (m, 2H), 7.12–7.10 (m, 2H), 2.27 (s, 3H), 2.08
(s, 3H), 1.92 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 191.73, 170.59, 153.21, 138.02, 129.12, 128.26,
125.80, 125.12, 25.32, 20.54, 14.11; GC-MS m/z (% rel
inten.): 233.08 (M+, 20.85), 117.90 (100); Anal. Calcd
for C13H15NO3: C, 66.94; H, 6.48; N, 6.00; Found: C,
67.12; H, 6.46; N, 6.11.
(E)-2-(Benzylamino)-4-oxopent-2-en-3-yl acetate
(4). Yellow dark brown viscous oil, IR νmax (KBr):
3396, 1715, 1675, 1600, 1580, 1432, 1215, 1027, 670,
1
cm−1; H NMR (400 MHz, CDCl3): δ 10.94 (s, 1H),
7.32–7.30 (m, 2H), 7.26–7.22 (m, 3H), 4.45–4.44 (d,
2H, J = 8.0 Hz), 2.21 (s, 3H), 1.99 (s, 3H), 1.83 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 190.5, 170.7,
156.3, 137.5, 128.7, 127.4, 126.6, 123.6, 46.8, 25.0,
(E)-2-(p-Tolylamino)-4-oxopent-2-en-3-yl acetate
(6). Dark brown viscous oil, IR νmax (KBr): 3458,
3330, 1741, 1692, 1588, 1395, 1375, 1230, 1135,
Heteroatom Chemistry DOI 10.1002/hc

Synthesis of 1-Acetoxy-2-aminoakenes via Condensation of Amino with Carbonyl and C C Acetoxylation 293
+
OH2
OH+
O
O
O
-H2O, -H+
H+
2a
HN
N
O
1a
13
14
O
15
OAc
Ph
I
H
N
O
N
DIB
16
O
AcO-
17
-PhI, AcO-
DIB
O
N
NH
O
O
N
OAc
-PhI, AcO-
AcO-
O
O
I
O
Ph
O
19
18
3
SCHEME 3 Possible reaction mechanism.
1
1010, 910, 808, 760, 678, cm−1; H NMR (400 MHz,
CDCl3): δ 12.10 (s, 1H), 7.16–7.14 (d, 2H, J = 8.0 Hz),
7.00–6.98 (d, 2H, J = 8.0 Hz), 2.34 (s, 3H), 2.27 (s,
3H), 2.07 (s, 3H), 1.89 (s, 3H);13C NMR (100 MHz,
CDCl3): δ 191.4, 170.6, 153.7, 135.8, 135.3, 129.7,
129.4, 125.2, 124.7, 119.9, 25.2, 20.9, 20.5, 14.0; GC-
MS m/z (% rel inten.): 247.02 (M+, 22.88), 131.89
(100); Anal. Calcd for C14H17NO3: C, 68.00; H, 6.93;
N, 5.66; Found: C, 68.13; H, 6.55; N, 5.74.
61.97; H, 9.29; N, 5.16; Found: C, 61.90; H, 9.33; N,
5.22.
(E)-3-(Butylamino)-1-oxo-1-phenylbut-2-en-2-yl
acetate (9). Orange viscous oil, IR νmax (KBr): 3311,
1725, 1685, 1605, 1515, 1472, 1377, 1275, 1015, 850,
1
705, cm−1; H NMR (400 MHz, CDCl3): δ 10.55 (s,
1H), 8.09–8.07 (q, 2H, J = 8.0 H), 7.56–7.53 (m, 1H),
7.46–7.42 (m, 2H), 3.44–3.39 (t, 2H, J = 8.0 H), 2.04
(s, 3H), 1.88 (s, 3H), 1.38–1.34 (m, 2H), 1.25–1.23
(m, 2H), 0.99–0.97 (t, 3H, J = 8.0 Hz); 13C NMR
(100 MHz, CDCl3): δ 195.70, 170.39, 133.82, 131.84,
130.85, 129.44, 128.73, 128.25, 50.03, 30.95, 20.61,
20.12, 13.75, 13.23; GC-MS m/z (% rel inten.): 99.94
(100); Anal. Calcd for C16H21NO3: C, 69.79; H, 7.69;
N, 5.09; Found: C, 69.88; H, 7.82; N, 5.31.
(E)-Ethyl 2-acetoxy-3-(butylamino)but-2-enoate
(7). Yellow viscous oil, IR νmax (KBr): 3350, 1695,
1664, 1439, 1375, 1250, 1021, 910, 890, 715, 690,
cm−1; H NMR (400 MHz, CDCl3): δ 10.52 (s, 1H),
1
4.26–4.22 (m, 2H), 3.80–3.77 (t, 2H, J = 8.0 Hz),
2.31 (s, 3H), 2.20 (s, 3H), 1.57–1.54 (m, 2H), 1.29–
1.27 (m, 5H), 0.87–0.85 (t, 3H, J = 8.0 Hz); 13C NMR
(100 MHz, CDCl3): δ 169.45, 164.47, 135.13, 128.12,
55.39, 44.34, 27.18, 26.47, 22.48, 20.82, 20.40, 13.96;
GC-MS m/z (% rel inten.): 243.29 (M+, 5.21), 83.88
(100); Anal. Calcd for C12H21NO4: C, 59.24; H, 8.70;
N, 5.76; Found: C, 59.45; H, 8.68; N, 5.90.
(E)-1-Oxo-1-phenyl-3-(phenylamino)but-2-en-2-
yl acetate (10). Dark brown viscous oil, IR νmax
(KBr): 3415, 1730, 1673, 1580, 1455, 1410, 1371,
1230, 1030, 805, 725, cm−1; 1H NMR (400 MHz,
CDCl3): δ 12.22 (s, 1H), 8.16–8.15 (q, 2H, J = 8.0
H), 7.60–7.57 (m, 1H), 7.46–7.38 (m, 7H), 1.69 (s,
3H), 1.53 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 195.57, 170.69, 141.88, 133.99, 130.95, 129.88,
128.54, 128.38, 128.25, 21.80, 13.29; GC-MS m/z (%
rel inten.): 235.93 (100); Anal. Calcd for C18H17NO3:
C, 73.20; H, 5.80; N, 4.74; Found: C, 73.03; H, 5.77;
N, 4.79.
(E)-Ethyl 2-acetoxy-3-(hexylamino)but-2-enoate
(8). Yellow viscous oil, IR νmax (KBr): 3332, 1705,
1682, 1473, 1399, 1255, 1015, 810, 740, 705, cm−1; 1H
NMR (400 MHz, CDCl3): δ 10.82 (s, 1H), 4.28–4.21 (q,
2H, J = 8.0 Hz), 3.81–3.79 (t, 2H, J = 8.0 Hz), 2.40
(s, 3H), 2.02 (s, 3H), 1.61–1.58 (m, 2H), 1.37–1.33
(m, 2H), 1.31–1.27 (m, 7H), 0.97–0.95 (t, 3H, J = 8.0
Hz); 13C NMR (100 MHz, CDCl3): δ 170.44, 164.99,
164.95, 135.14, 128.14, 55.39, 44.08, 32.91, 20.82,
20.03, 14.23, 14.17, 13.67, 10.90; GC-MS m/z (% rel
inten.): 111.92 (100); Anal. Calcd for C14H25NO4: C,
(E)-3-(p-Tolylamino)-1-oxo-1-phenylbut-2-en-2-
yl acetate (11). Dark brown viscous oil, IR νmax
(KBr): 3430, 1735, 1688, 1615, 1572, 1498, 1422,
1382, 1255, 1015, 908, 850, 773, 695, cm−1; 1H
NMR (400 MHz, CDCl3): δ 12.09 (s, 1H), 8.14–8.13
Heteroatom Chemistry DOI 10.1002/hc

294 Liu, Chen, and Zhang
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(m, 2H), 7.58–7.56 (m, 1H), 7.56–7.55 (m, 2H), 7.47–
7.22 (m, 4H), 2.37 (s, 3H), 1.67 (s, 3H), 1.50 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 195.59, 170.83, 139.26,
138.63, 133.93, 131.98, 130.93, 130.42, 128.35,
127.94, 119.93, 21.72, 21.11, 13.26; GC-MS m/z (%
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acetate (12). Orange viscous oil, IR νmax (KBr):
3310, 1712, 1691, 1622, 1512, 1465, 1395, 1270,
1010, 912, 785, 700, cm−1; 1H NMR (400 MHz,
CDCl3): δ 12.13 (s, 1H), 8.07–8.05 (m, 2H), 7.44–7.41
(m, 2H), 3.43–3.42 (m, 1H), 3.31–3.32 (m, 1H), 1.89
(s, 3H), 1.62–1.60 (m, 2H), 1.49 (s, 3H), 1.32–1.33
(m, 6H), 0.90–0.88 (t, 3H, J = 8.0 Hz);13C NMR
(100 MHz, CDCl3): δ 195.72, 170.37, 133.80, 131.83,
130.84, 128.24, 127.73, 127.28, 50.29, 31.45, 28.87,
26.57, 22.56, 20.62, 13.96, 13.24; GC-MS m/z (% rel
inten.): 128.05 (100); Anal. Calcd for C18H25NO3: C,
71.26; H, 8.31; N, 4.62; Found: C, 71.44; H, 8.23; N,
4.79.
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