An efficient preparation of N-acetyl enamides catalyzed by Ru(II) complexes

Article abstract of DOI:10.1016/j.tet.2012.10.027

Reductive acetylation of ketoximes to give the corresponding acyl enamides can be achieved by using 1-3 mol % of [RuCl₂(p-cymene)]₂ as the catalyst in the presence of KI as the reducing agent in high yields. This procedure has been applied to synthesize N-[1-(1,3-benzodioxol-5-yl)-1-butenyl] acetamide (6), which is the intermediate for the synthesis of DMP 777, an inhibitor of leukocyte elastase.

Full text of DOI:10.1016/j.tet.2012.10.027

Tetrahedron 69 (2013) 268e273
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient preparation of N-acetyl enamides catalyzed by Ru(II)
complexes
*
Kaliyappan Murugan, Da-wei Huang, Yu-Ting Chien, Shiuh-Tzung Liu
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 August 2012
Received in revised form 1 October 2012
Accepted 9 October 2012
Available online 16 October 2012
Reductive acetylation of ketoximes to give the corresponding acyl enamides can be achieved by using
1e3 mol % of [RuCl2(p-cymene)]2 as the catalyst in the presence of KI as the reducing agent in high yields.
This procedure has been applied to synthesize N-[1-(1,3-benzodioxol-5-yl)-1-butenyl]acetamide (6),
which is the intermediate for the synthesis of DMP 777, an inhibitor of leukocyte elastase.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Acetylation
Ruthenium
Enamide
Oxime
O
Cl
Cl
N
DMP 777
O
O
N
P
N
H
HO
1. Introduction
O
O
OH
N
O
NH
N-Acetylenamidesarekeystructuralmotifsforsynthesisofvarious
classes of natural products as well as valuable synthetic intermediates
for pharmaceutical drug candidates such as inhibitor of leukocyte
elastase, GABA-B antagonist, acetylcholinesterase inhibitor, G-protein
O
CGP 55845
(GABA -B antagonist
)
O
Cl
OH
H
EtO2C
O
N
F
coupled receptor, b-adrenergic receptor agonist, and anti-arrhythmia
HCl
Cl
agent (Fig. 1).1 In addition, N-acetyl enamides are important pre-
cursors for the enantioselective hydrogenation to synthesize various
chiral amine building blocks in long standing strategy.1 In recent re-
ports, these substrates are also utilized as precursors in catalytic
asymmetric CeC and CeN bond forming reactions.2,3 In spite of the
extensive applications of N-acetyl enamides, preparations of this class
of compounds still remain as a challenging work.
O
Cl
(β−Adrenergic receptor agonist)
SR 58611A
CHF2
HN
O
N
N
H
O
NHMs
Bradykinin B1
(Antagonist)
OMe
OH
Me
N
O
O
Et
NMe2
There are number of methods that have been employed for the
synthesis of N-acetyl enamides, including addition of Grignard re-
agent or methyl lithium to nitriles followed by quench of an imine
with acetic anhydride,4 transition metal catalyzed cross coupling of
vinyl triflates or tosylates with amides5 and Heck reaction of aryl
triflates or halides with N-vinylacetamides,6 direct condensation of
amides with ketones.7 However, these methods show certain
drawbacks such as less functional group tolerance, longer reaction
time, higher catalyst loading, some of the reactions required low
temperature and additional ligand for a better conversion.
O
N
HCl
SDZ-ENA-713
(Acetylcholinesterase inhibitor)
MK-0499
NC
(Antiarrhthymia agent)
Fig. 1. Some drug molecules synthesized from enamides.
the most efficient way.8 Reductive acylation of ketoximes to N-acetyl
enamides offers an alternative way and ought to be an atom-
economy method. A number of reducing agents such as iron
powder,9 Cr(OAc)2,10 Ti(OAc)3,10 Fe(OAc)2,11 triethylphospine,12 and
molecular hydrogen13 have been utilized in this transformation.
Nevertheless, these procedures show some disadvantages for the
preparation such as highly exothermic reaction conditions, pyro-
phoric reagents, and less substrate scope. Very recently, Guan and
co-workers have reported a Cu(I) catalyzed reductive acylation of
Direct titanium-mediated conversion of ketones into enamides
with NH3 and acetic anhydride reported byReevesand co-workersis
* Corresponding author. E-mail address: stliu@ntu.edu.tw (S.-T. Liu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.027

K. Murugan et al. / Tetrahedron 69 (2013) 268e273
269
ketoxime to enamides with the use of sodium bisulfite as the re-
ducing agent.14 This process demonstrates a practical manner and
provides a broad scope of enamides in high yields. In this work, we
would like to report anotherefficient catalytic system by using Ru(II)
for reductive acylation of various cyclic and acyclic ketoximes to N-
acetyl enamides in the presence of KI or NaHSO3 as reducing agents.
pleasure, [RuCl2(p-cymene)]2 proved to be an effective catalyst for
this transformation. At 5 mol % catalyst loading of [RuCl2(p-cym-
ene)]2 in toluene over 5 h, reaction afforded 70% yield of enamide
1a (Table 1, entry 9). Therefore, this catalyst was further studied by
variation of reaction conditions to improve the production of 1a. In
place of toluene with DCE as the solvent, a complete conversion of
starting material was observed, providing 1a in 87% yield (Table 1,
entry 10). Further solvent screening, acetonitrile appeared unsuit-
able for the catalysis, but DME was compatible with this reaction
albeit in low yield (Table 1, entries 13 and 14). Lowering the catalyst
loading down to 1 mol %, the product conversion remained similar,
but the reaction time took little longer (Table 1, entries 11 and 12).
In addition several reductants such as KI, molecular H2, and FeSO4
were investigated, revealing that KI is also effective even with the
use of 1.0 equiv of the reagent (Table 1, entries 15 and 16).
With the optimized reaction condition in hand, the scope of the
reductive acylation with various acyclic ketoximes was investigated
(Table 2). The reactions with chloro and bromo substituted aromatic
ketoximes proceeded smoothly to give the desired enamides 1be1e in
good yields at a shorter reaction time. For the substitution effect, we
observed that ortho and para substituted bromo ketoximes had similar
reactivity, but in the case of the meta substituted one showed little less
reactivity. When fluoro and iodo substituted aromatic ketoximes were
examined under the optimized condition, the reaction took place very
rapidly and some of the undesired product formed with the use of KI as
a reducing agent, to avoid that we changed to NaHSO3 then reaction
proceeded smoothly and yielded desired enamides 1fe1g in good
yields. Electron donating groups such as alkyl and methoxy substituted
aromatic ketoximes exhibited high reactivity to afford corresponding
enamides in slightly higher yields than electron withdrawing nitro
group substituted aromatic ketoximes (Table 2, entries 6e9). Notably,
the reaction with 1-(4-aminophenyl)ethanone oxime gave the amine
protected enamide in high yield (1m). The nitrile functionality is tol-
erable in this condition and the corresponding enamide obtained in
2. Results and discussion
Rhodium and ruthenium complexes are known as promising
catalysts in many organic transformations.15 Thus, we took the
opportunity to utilize some common Rh(I) and Ru(II) complexes in
our course of research. At the outset, acetophenone oxime was
chosen as a model substrate for initial screening (Eq. 1). In a typical
experiment, a mixture of acetophenone oxime (1.0 equiv), acetic
anhydride (2.0 equiv), NaHSO3 (2.0 equiv), and a metal complex in
an organic solvent was heated to reflux for a certain period. No
desired product was observed with the use of Rh2(OAc)4 as the
catalyst (Table 1, entry 1). Then various rhodium complexes were
screened for this purpose under similar reaction conditions. How-
ever, RhCl(PPh3), Rh(CO)2(acac), and Rh(acac)(COD) (Table 1, en-
tries 3e5) gave unsatisfying results, only [Rh(COD)Cl]2 provided the
desired product 1a in moderate yield 42% (Table 1, entry 2).
O
OH
N
HN
Catalyst, reductant
(1)
Ac2O, Solvent
1a
Table 1
Optimization of the N-acetyl enamide synthesisa
Entry Catalyst (loading)
Reductant Solvent
t, h Yield,b
moderate yield. The reaction was tolerant with
a-mono and di-
(%)
substituted acyclic ketoxime (entries 12 and 13), in the case of pro-
piophenone oxime gave the corresponding enamide as mixture of E/Z
(1:2) isomers (1p). The reductive acylation reaction was compatible
with bicyclic, heteroaromatic, and aliphatic acyclic ketoximes to afford
the corresponding enamides in good to moderate yields (1qe1s). In
1
2
3
4
5
6
7
8
Rh2(OAc)2 (10 mol %)
NaHSO3
NaHSO3
NaHSO3
NaHSO3
NaHSO3
NaHSO3
NaHSO3
NaHSO3
Toluene 12
Toluene 12
0
42
0
5
10
0
60
50
70
87
85
85
0
60
90
89
50
0
[Rh(COD)Cl]2 (10 mol %)
RhCl(PPh3)3 (10 mol %)
Rh(CO)2(acac) (10 mol %)
Rh(acac)(COD) (10 mol %)
Ru(dppe)2Cl2 (10 mol %)
Ru(CO)3Cl2(THF) (5 mol %)
Ru(DMSO)4Cl2 (5 mol %)
Toluene 12
Toluene 20
Toluene 20
Toluene 20
Toluene 20
Toluene 20
9
[RuCl2(p-cymene)]2 (5 mol %) NaHSO3
[RuCl2(p-cymene)]2 (5 mol %) NaHSO3
[RuCl2(p-cymene)]2 (3 mol %) NaHSO3
[RuCl2(p-cymene)]2 (1 mol %) NaHSO3
[RuCl2(p-cymene)]2 (1 mol %) NaHSO3
[RuCl2(p-cymene)]2 (1 mol %) NaHSO3
[RuCl2(p-cymene)]2 (1 mol %) KI
Toluene
DCEe
DCE
5
7
Table 2
10
11
12
13
14
15
16
17
18
Scope of enamide formation with acyclic ketoximea
12
15
24
24
3
DCE
Entry
1
Enamide
NHAc
Method
t, h
Yield,b
89
%
CH3CN
DMEe
DCE
A
3
[RuCl2(p-cymene)]2 (1 mol %) KIc
[RuCl2(p-cymene)]2 (1 mol %) H2
[RuCl2(p-cymene)]2 (1 mol %) FeSO4
DCE
3
d
1a
DCE
DCE
24
24
NHAc
a
Reaction conditions: acetophenone oxime (1.0 equiv), reductant (2.0 equiv),
Ac2O (2.0 equiv), solvent at reflux.
2
A
5
70
b
Isolated yields.
KI used 1.0 equiv.
1.0 atm.
1b
c
Cl
d
e
DCE¼1,2-dichloroethane, DME¼dimethoxyethane.
NHAc 1c o-
1d m-
A
A
A
3
3
3
88
72
89
3
4
With these disappointing results on Rh(I) catalysts, we switched
over to utilize Ru(II) complexes for this transformation. Under
similar reaction conditions, Ru(dppe)2Cl2 (10 mol %) exhibited to be
an ineffective catalyst (Table 1, entry 6), but Ru(CO)3Cl2(THF) and
Ru(DMSO)4Cl2 even 5 mol % afforded the desired enamide products
in 60% and 50% yields, respectively (Table 1, entries 7 and 8). At-
tempts to improve the conversion with these complexes by keeping
longer reaction time or reaction temperature failed. To our
Br
1e p-
NHAc
B
15
83
(continued on next page)
1f
F

270
K. Murugan et al. / Tetrahedron 69 (2013) 268e273
Table 2 (continued )
addition to acetic anhydride, the reaction occurred equally well with
Yield,b
82
%
propionic anhydride (Table 2, entry 17).
The general applicability of the ruthenium catalyzed reductive
acylation of cyclic ketoximes leading to N-acetyl enamides is dem-
Entry
Enamide
NHAc
Method
B
t, h
onstrated. Under the optimized condition,
none oxime derivatives showed high yields (Table 3, entries 1e3). For
the substrate of -tetralone oxime, the reaction appeared to be fairly
a-tetralone and a-inda-
5
20
1g
I
a
slow with 1 mol % of [RuCl2(p-cymene)]2. However, the reaction
reached the complete conversion within 12 h by increasing the cat-
alyst loading upto 3e5 mol%. The efficiencyof thereductive acylation
of non-benzylic cyclic ketoximes was compatible with benzylic cyclic
ketoximes. Five-, six-, and seven-membered cyclic ketoximes affor-
ded the corresponding enamides in good yields at shorter reaction
times. Thus, cyclopentanone, cyclohexanone, and cycloheptanone
oximes were reductively acetylated to give the corresponding N-
acetyl enamides 2d, 2e, and 2f, respectively (Table 3, entries 4e6).
Furthermore, the substituted cyclic ketoximes substrates also well
tolerated under this developed condition to yield the corresponding
enamides in good to moderate yields (Table 3, entries 7 and 8).
NHAc
6
7
A
A
1
4
85
73
1h
NHAc
1i
nBu
NHAc
1j p-
1k m-
A
A
3
3
85
82
8
MeO
Table 3
Scope of enamide formation with cyclic ketoximea
NHAc
Entry
1c
Enamide
t, h
Yield,b
81
%
9
B
A
B
B
20
2
75
81
60
75
1l
O2N
12
NHAc
10
11c
12
2d
12
12
84
78
1m
AcHN
NC
NHAc
3
12
4
1n
4
5
6
2
5
3
71
60
72
NHAc
1o
NHAc
75 E/Z¼2:1
7
4
4
77
13
14
B
B
8
1p
NHAc
24
70
NHAc
2h
8
65e
1q
NHAc
a
Reaction conditions: oxime (1.0 equiv), NaHSO3 (2.0 equiv), Ac2O (2.0 equiv) and
15d
16
S
B
B
12
6
66
Ru catalyst (1 mol %) in DCE under refluxing.
1r
b
Isolated yields.
Catalyst 5 mol %.
Catalyst 3 mol %.
The ratio of regio-isomers is ca. 2:1.
c
d
NHAc
e
60 E/Z¼1:1.5
1s
The significance of this ruthenium catalyzed reductive acylation
reaction isfurtherexploited by the synthesis ofenamide intermediate
6, which is used to prepare leukocyte elastase inhibitor DMP 777.16 As
shown in Scheme 1, the enamide 6 was synthesized starting from 1,2-
methylendioxybenzene 3. Electrophilic aromatic acylation of 3 with
butyric anhydride in the presence of BF3 gave the butanone com-
pound 4 in 85% yield. Subsequently, compound 4 was converted into
the corresponding oxime by treatment of hydroxylamine in the
presence of sodium acetate. Under the optimized reductive acylation
conditionsdeveloped in this work, compound 5 was transformed into
the desired N-acetyl enamide 6 in good yield.
NHCOEt
17e
A
4
77
1t
a
Conditions: method A: oxime (1.0 equiv), KI (1.0 equiv), Ac2O (2.0 equiv), DCE at
reflux. Method B: oxime (1.0 equiv), NaHSO3 (2.0 equiv), Ac2O (2.0 equiv), DCE at
reflux temperature.
b
Isolated yields.
Catalyst 5 mol %.
Catalyst 3 mol %.
c
d
e
Instead of acetic anhydride, propionic anhydride was used.

K. Murugan et al. / Tetrahedron 69 (2013) 268e273
271
O
dried over MgSO4 and concentrated under reduced pressure. The
crude product was purified by column chromatography on silica gel
with hexane/ethyl acetate as eluent to yielded the desired enamide
1a (109 mg, 0.676 mmol) in 89% yield. Products obtained in this work
O
O
(n-PrCO)2O
NH2OH.
98%
O
O
BF3.OEt2
85%
3
4
O
were characterized by spectral methods particularly with 1H and 13
C
OH
N
HN
NMR, and the data were consistent with those reported. Selected
spectral data for enamides are presented below and other spectral
data are collected in Supplementary data.
Ru catalyst
O
O
O
NaHSO3, Ac2O
70%
O
6
5
3.2.1. N-(1-Phenylvinyl)acetamide (1a).11 1H NMR (400 MHz, CDCl3)
DMP 777
ref. 15
d
7.38e7.29 (m, 5H), 7.07 (br s, 1H), 5.78 (s, 1H), 5.04 (s, 1H), 2.04 (s,
Scheme 1. Synthetic approach to DMP 777.
3H); 13C NMR (100 MHz, CDCl3)
d 169.21, 140.5, 138.3, 128.6, 126.0,
102.6, 24.4; HRMS-ESI-MS (m/z) [MþH]þ: calcd for C10H12NO:
162.0919; found 162.0916.
A plausible mechanism for the Ru(II)-catalyzed reductive acyl-
ation of ketoximes is shown in Scheme 2, which is similar to that
Cu(I)-catalyzed reaction.14 Acylation of ketoxime provides the cor-
responding O-acetyloxime, which is subsequently reduced by Ru(II)
to yield the iminium anion. Acylation of the iminium anion fol-
lowed by tautomerization provides the desired product.
3.2.2. N-(1-(4-Chlorophenyl)vinyl)acetamide
(1b).17 1H
NMR
(400 MHz, CDCl3) 7.31 (s, 4H), 6.86 (br s, 1H), 5.75 (s, 1H), 5.06 (s,
d
1H), 2.09 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 169.0, 139.5, 136.7,
134.6, 128.8, 127.3, 103.5, 24.4; HRMS-ESI-MS (m/z) [MþH]þ: calcd
for C10H11ClNO: 196.0529; found 196.0527.
In summary, we have demonstrated the efficiency of ruthenium
catalysts on the reductive acylation of various cyclic and acyclic
ketoximes. This method provides a practical protocol for the
preparation of N-acyl enamides with less catalyst loading and re-
action time. By adopting this method, we have successfully pre-
pared N-(1-(benzo[d][1,3]dioxol-5-yl)but-1-enyl)-acetamide 6,
a key intermediate leading to DMP 777. Current research is focused
on extending the usage of enamide in the preparation of hetero-
cyclic compounds.
3.2.3. N-(1-(2-Bromophenyl)vinyl)acetamide
(400 MHz, CDCl3)
7.54 (d, J¼7.9 Hz, 1H), 7.34e7.27 (m, 2H),
7.20e7.16 (m, 1H), 6.83 (br s, 1H), 5.94 (s, 1H), 4.76 (s, 1H), 2.02 (s,
(1c). 1H
NMR
d
3H); 13C NMR (100 MHz, CDCl3)
d 168.6, 140.2, 139.4, 133.1, 131.4,
130.0, 127.6, 121.8, 104.3, 24.4; HRMS-ESI-MS (m/z) [MþH]þ: calcd
for C10H11BrNO: 240.0024; found 240.0027.
3.2.4. N-(1-o-Tolylvinyl)acetamide (1h).8 1H NMR (400 MHz, CDCl3)
d
7.25e7.14 (m, 4H), 6.68 (br s, 1H), 6.01 (s, 1H), 4.66 (s, 1H), 2.32 (s,
3H), 1.99 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
168.5, 140.2, 138.5,
135.7, 130.4, 129.1, 128.5, 125.9, 102.3, 24.4, 19.4; HRMS-ESI-MS (m/
z) [MþH]þ: calcd for C10H14NO: 176.0075; found 176.0074.
LnRuII
NOAc
N
NOH
3.2.5. N-(1-(4-Butylphenyl)vinyl)acetamide (1i). 1H NMR (400 MHz,
R
R
R
CDCl3)
d
7.30 (d, J¼7.8 Hz, 2H), 7.15 (d, J¼8.1 Hz, 2H), 6.86 (br s, 1H),
reductant
LnRuII
LnRuII
5.81 (s, 1H), 5.03 (s, 1H), 2.59 (t, J¼7.6 Hz, 2H), 2.09 (s, 3H),1.61e1.53
LmRuIII
(m, 2H), 1.36e1.23 (m, 2H), 0.9 (t, J¼7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 168.9, 143.6, 140.3, 135.7, 128.7,125.8, 101.7, 35.2, 33.5, 24.6,
NHAc
NAc
N
22.3, 13.9; HRMS-ESI-MS (m/z) [MþH]þ: calcd for C14H20NO:
R
218.1545; found 218.1547.
R
R
Scheme 2. Reaction pathway for the reductive acylation of ketoximes.
3.2.6. N-(2-Methyl-1-phenylprop-1-enyl)acetamide (1o).11 1H NMR
(400 MHz, DMSO)
d
9.01 (s, 1H), 7.31e7.20 (m, 5H), 1.89 (s, 3H), 1.71
167.9, 139.5, 129.2,
(s, 3H), 1.70 (s, 3H); 13C NMR (100 MHz, DMSO)
d
128.4, 128.1, 127.8, 127.1, 23.1, 21.1, 21.0; HRMS-ESI-MS (m/z)
[MþH]þ: calcd for C12H16NO: 182.1154; found 182.1153.
3. Experimental
3.1. General information
3.2.7. (E/Z)
N-(1-Phenylvinyl)propionamide
(1p).11 1H
NMR
(400 MHz, CDCl3) (w2:1 mixture of geometric isomers)
d
7.41e7.20
All reactions were carried out in a 10 mL reaction tube. Chemicals
were purchased from Aldrich and Acros and unless otherwise noted
were used without further purification. Enamides were purified by
(m, 5H), 6.86/6.70 (br s, 1H), 6.04/5.92 (q, J¼7.0 Hz, 1H), 2.12 (s, 3H),
1.82/1.72 (d, J¼7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 173.4,168.3,
chromatography. All new compounds were characterized by 1H, 13
C
138.0, 135.6, 133.9, 128.6, 128.3, 128.1, 127.6, 125.3, 125.2, 122.1,
121.2, 23.2, 20.4, 13.9, 13.5; HRMS-ESI-MS (m/z) [MþH]þ: calcd for
C11H14NO: 176.1075; found 176.1073.
NMR and HRMS and their spectra are deposited in Supplementary data.
3.2. General procedure for the ruthenium(II) catalyzed re-
ductive acylation of ketoxime to enamides
3.2.8. N-(1-(Thiophen-2-yl)vinyl)acetamide
(400 MHz, CDCl3),
7.19 (d, J¼4.4 Hz, 1H), 7.06 (d, J¼4.2 Hz, 1H),
6.96 (t, J¼4.5 Hz, 1Hþ1H for NH), 5.73 (s, 1H), 5.20 (s, 1H), 2.09 (s,
(1r).18 1H
NMR
d
A reaction tube was charged with acetophenone oxime (100 mg,
0.739 mmol), KI (122 mg, 0.739 mmol), and [RuCl2(p-cymene)]2
(4.5 mg, 0.0074 mmol). To that DCE (2 mL) and acetic anhydride
(151 mg, 1.47 mmol) were added by syringe. The reaction mixture
was stirred at reflux under N2 as indicated time in the Tables 1e3.
The reaction mixture was cooled down to rt, diluted with 10 mL of
ethyl acetate, and washed with 10% NaOH solution. The organic layer
3H); 13C NMR (100 MHz, CDCl3)
d 168.8, 141.6, 134.1, 127.4, 125.2,
123.6, 102.8, 24.5; HRMS-ESI-MS (m/z) [MþH]þ: calcd for
C8H10NOS: 168.0483; found 168.0478.
3.2.9. (E/Z) N-(Hept-3-en-4-yl)acetamide (1s). 1H NMR (400 MHz,
CDCl3) (w1:1.5 mixture of geometric isomers)
d 6.51 (br s,1H), 5.73/
5.00 (t, J¼6.9 Hz, 1H), 2.22e2.14 (m, 2H), 2.04e1.89 (m, 5H),

272
K. Murugan et al. / Tetrahedron 69 (2013) 268e273
1.43e1.35 (2H), 0.95e0.89 (m, 6H); 13C NMR (100 MHz, CDCl3)
the TLC), the reaction mixture was cooled to rt and then water was
added. The mixture was extracted with EtOAc (2ꢂ10 mL) and the
combined organic extracts were dried over MgSO4, filtered, and
concentrated under reduced pressure. The desired product 5 was
obtained as white solid (1.05 g, 98%). The crude product is pure
enough to carry out next stage without purification. 1H NMR
(400 MHz, CDCl3), 7.08e7.03 (m,12H), 6.79 (d, J¼8.1 Hz,1H), 5.96 (s,
1H), 2.72 (t, J¼7.8 Hz, 2H), 1.60e1.54 (m, 2H), 0.95 (t, J¼7.3 Hz, 3H);
13C NMR (100 MHz, CDCl3) 159.3, 148.5, 147.9, 129.8, 120.5, 108.2,
106.5, 101.3, 28.3, 19.8, 14.2; HRMS-ESI-MS (m/z) [MþH]þ: calcd for
C11H14O3: 208.0974; found 208.0973.
d
168.6, 168.2, 133.6, 128.9, 123.6, 120.4, 36.9, 31.5, 24.3, 23.6, 21.1,
20.6, 20.3, 14.5, 13.7, 13.6, 13.5; HRMS-ESI-MS (m/z) [MþH]þ: calcd
for C9H18NO: 156.1388; found 156.1382.
3.2.10. N-(3,4-Dihydronaphthalen-1-yl)acetamide (2a).11 1H NMR
(400 MHz, DMSO) d 9.10 (s, 1H), 7.19e7.16 (m, 4H), 6.16 (s, 1H), 2.68
(t, J¼7.8 Hz, 2H), 2.26e2.66 (m, 2H), 2.02 (s, 3H); 13C NMR
(100 MHz)
32.3, 28.5.
d 174.0,141.2,137.6,136.9,132.6,132.3,131.2,127.3,124.2,
3.2.11. N-Cyclohexenylacetamide (2e).14 1H NMR (400 MHz, CDCl3)
6.44 (br s, 1H), 6.01 (s, 1H), 2.09e2.08 (m, 4H), 1.97 (s, 3H),
1.66e1.63 (m, 2H), 1.56e1.51 (m, 2H); 13C NMR (100 MHz, CDCl3)
d
3.5. N-(1-(Benzo[d][1,3]dioxol-5-yl)but-1-enyl)acetamide
(6)16
d
168.3, 132.5, 113.2, 28.0, 24.4, 23.9, 22.5, 21.9; HRMS-ESI-MS (m/z)
[MþH]þ: calcd for C8H14NO: 140.1075; found 140.1076.
A reaction tube was charged with 1-(benzo[d][1,3]dioxol-5-yl)
butan-1-one oxime 5 (100 mg, 0.482 mmol), NaHSO3 (100 mg,
0.965 mmol), and [RuCl2(p-cymene)]2 (2.9 mg, 0.0048 mmol). To
that, DCE (2 mL) and acetic anhydride (98 mg, 0.965 mmol) were
added by syringe. The reaction mixture was stirred at reflux under
N2 for 12 h. The reaction mixture was cooled down to rt, diluted
with 10 mL of ethyl acetate, and washed with 10% NaOH solution.
The organic layer dried over MgSO4 and concentrated under re-
duced pressure. The crude product was purified by column chro-
matography on silica gel with hexane/ethyl acetate as eluent to
yielded the desired enamide 6 (39.0 mg, 70%). 1H NMR (400 MHz,
DMSO), 9.01 (s, 1H), 6.92 (s, 1H), 6.84 (s, 2H), 5.99 (s, 2H), 5.70 (t,
J¼7.1 Hz, 1H), 2.08e2.00 (m, 2H), 1.98 (s, 3H), 0.98 (t, J¼7.5 Hz, 3H);
13C NMR (100 MHz, CDCl3) 168.4, 147.8, 146.9, 133.3, 133.2, 125.8,
119.2, 108.3, 106.0, 101.4, 23.1, 21.5, 13.9; HRMS-ESI-MS (m/z)
[MþH]þ: calcd for C13H16NO3: 234.1130; found 234.1129.
3.2.12. N-Cycloheptenylacetamide (2f). 1H NMR (400 MHz, CDCl3),
d
6.67 (br s, 1H), 6.07 (t, J¼6.7 Hz, 1H), 2.26 (t, J¼5.2 Hz, 2H),
2.06e2.08 (m, 2H), 1.96 (s, 3H), 1.67e1.68 (m, 2H), 1.47e1.56 (m,
4H); 13C NMR (100 MHz, CDCl3)
d 168.5, 139.2, 118.7, 33.6, 31.9, 26.9,
26.6, 25.9, 24.2; HRMS-ESI-MS (m/z) [MþH]þ: calcd for C9H16NO:
154.1232; found 154.1233.
3.2.13. N-(4-tert-Butylcyclohex-1-enyl)acetamide (2g).11 1H NMR
(400 MHz, CDCl3),
d
6.57 (br s, 1H), 6.00 (t, J¼2.6 Hz, 1H), 2.18e2.09
(m, 3H), 1.97 (s, 3H), 1.84e1.77 (m, 2H), 1.23e1.20 (m, 2H), 0.82 (s,
9H); 13C NMR (100 MHz, CDCl3)
d 168.3, 132.5, 113.2, 43.6, 32.1, 29.4,
27.2, 25.4, 24.3, 23.8; HRMS-ESI-MS (m/z) [MþH]þ: calcd for
C12H22NO: 196.1701; found 196.1698.
3.2.14. N-(3-Methylcyclohex-1-enyl)acetamide
(400 MHz, CDCl3) (w2:1 mixture of regio-isomers)
(2h). 1H
NMR
d
8.69 (br s, 1H),
Acknowledgements
5.97/5.90 (s, 1H), 2.19e2.08 (m, 3H), 1.74 (s, 3H), 1.71e1.43 (m, 3H),
1.09e1.06 (m, 1H), 0.92 (t, J¼3.2 Hz, 3H); 13C NMR (100 MHz, CDCl3)
168.3,133.6,133.5,116.2,109.5, 36.0, 31.0, 30.4, 29.3, 28.5, 27.6, 24.3,
24.2, 23.8, 22.8, 22.0, 21.3; HRMS-ESI-MS (m/z) [MþH]þ: calcd for
C9H16NO: 154.1232; found 154.1234.
We thank the National Science Council (NSC100-2113-M-002-
001) for the financial support. We also thank to Miss. Yu Chang
Chao for her generous support for in ESI mass data analysis.
Supplementary data
3.3. 1-(Benzo[d][1,3]dioxol-5-yl)butan-1-one (4)16
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.10.027.
A pre-dried two-neck round bottom flask was charged with 1,2-
methylenedioxy benzene (2.0 g, 16.37 mmol), 1,2-dichloroethane
(7 mL) and n-butyric anhydride (3.2 mL, 19.6 mmol). The result-
ing mixture was cooled to ꢀ10 ꢁC, to that BF3$Et2O (6.78 g,
1.38 mmol) was added by slow addition over 15 min, while main-
taining the temperature ꢀ5 ꢁC to 0 ꢁC. After the addition, the re-
action mixture was stirred at ꢀ5 ꢁC for 3 h. The reaction was then
quenched with sodium acetate solution, the organic layer was
separated and washed with 5% NaOH (7 mL) followed by water. The
organic layers were concentrated and the crude product was pu-
rified by column chromatography using on silica gel with hexane/
ethyl acetate (10%) as eluent to yielded the desired compound 4
(1.34 g, 85%). 1H NMR (400 MHz, CDCl3), 7.52 (dd, J¼8.1, 1.6 Hz, 1H),
7.40 (d, J¼8.1 Hz, 1H), 6.80 (d, J¼8.1 Hz, 1H), 5.99 (s, 1H), 2.82 (t,
J¼7.3 Hz, 2H), 1.70 (h, J¼7.4 Hz, 2H), 0.95 (t, J¼7.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) 198.4, 151.5, 148.1, 132.0, 124.1, 107.8, 107.7, 101.7,
40.2, 18.0, 13.8; HRMS-ESI-MS (m/z) [MþH]þ: calcd for C11H13O3:
193.0865; found 193.0867.
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