Iodine-mediated oxidative dehydrogenation of β-acylamino ketones for the highly stereoselective synthesis of (Z)-β-keto-enamides

Article abstract of DOI:10.1055/s-0035-1561582

An iodine-mediated oxidative dehydrogenation of β-acylamino ketones has been developed for the synthesis of β-ketoenamides in moderate to good yields. Only Z-isomers are accessed due to the intramolecular H-bonding interaction in the HI-elimination step.

Full text of DOI:10.1055/s-0035-1561582

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Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
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letter
Synlett
H.-H. Chang et al.
Letter
Iodine-Mediated Oxidative Dehydrogenation of β-Acylamino
Ketones for the Highly Stereoselective Synthesis of (Z)-β-Keto-
enamides
Hong-Hong Changa
Fei Hua
Wen-Chao Gao*a
Tao Liua
Xing Lia
Wen-Long Weia
Yan Qiao*b
O
I2 (1.2 equiv)
O
DABCO (3 equiv)
R3
O
HN
R3
O
HN
p-xylene, 60 °C
R1
R2
R1
R2
Z
•
iodine-mediated dehydrogenation
• Z-selective synthesis of β-ketoenamides
•
19 examples, up to 78% yield
1
= Ar, R2 = Ar
= Me, Ph, OEt, OBn
R
R
3
a
College of Chemistry and Chemical Engineering, Taiyuan University
of Technology, Taiyuan 030024, P. R. of China
gaowenchao@tyut.edu.cn
State Key Laboratory of Coal Conversion, Institute of Coal Chemis-
b
try, Chinese Academy of Sciences, Taiyuan 030001, P. R. of China
qiaoy@sxicc.ac.cn
9
b
Received: 14.01.2016
Accepted after revision: 26.02.2016
Published online: 14.03.2016
asymmetric synthesis of chiral 4H-1,3-oxazines,
and
3c
preparation of pyrimidines. However, the successful ex-
DOI: 10.1055/s-0035-1561582; Art ID: st-2016-w0028-l
amples on the stereoselective synthesis of the Z-isomer
without the use of transition-metal catalysts are rare.
10
Abstract An iodine-mediated oxidative dehydrogenation of β-acyl-
amino ketones has been developed for the synthesis of β-ketoenamides
in moderate to good yields. Only Z-isomers are accessed due to the in-
tramolecular H-bonding interaction in the HI-elimination step.
Therefore, from an economical and an environmental point
of view, it is highly desirable to develop a mild and metal-
free method for the stereoselective synthesis of (Z)-β-ke-
toenamides from readily available starting materials.
Recently, molecular iodine has served as an eco-friendly
reagent to achieve numerous oxidative transformations,
Key words molecular iodine, dehydrogenation, β-acylamino ketones,
β-ketoenamide, Z-selectivity
1
1
12
such as aromatization, carbon–carbon (C–C) bond, and
β-Ketoenamides derivatives as versatile building blocks
carbon–heteroatom bond formation.13 During our studies
in organic synthesis have been used widely for the prepara-
tion of a variety of chiral 1,3-amino alcohols, natural prod-
on I -catalyzed C–O bond formation for the synthesis of ox-
azolines and oxazoles (Scheme 1, a), we found that when
2
1
14a
2
3a
ucts, and heterocyclic derivatives, including oxazoles, py-
the reaction base was switched to 1,4-diazabicyc-
lo[2.2.2]octane (DABCO), the stereoselective dehydrogena-
tion of β-acylamino ketones, readily available compounds
3b
3c
3d,f
3g
rimidin-2-ones,
pyrimidines, pyridines,
pyrroles,
3
f
etc. In view of their importance, considerable efforts have
been made for their syntheses. Conventional methods to
access this class of compounds include N-acylation of β-ke-
15
derived from simple ketones, nitriles, and aldehydes, pro-
ceeded to provide β-ketoenamides as single Z-isomers me-
diated by molecular iodine (Scheme 1, b). These significant
differences might be attributable to the distinctive proper-
4
1
toenamines, condensation of 1,3-diketones with amides,
NaOH-catalyzed rearrangement of propargylic hydroxyl-
amines, Brønsted acid catalyzed Meyer–Schuster rear-
3c
ties of DABCO (e.g., pK value, nucleophilicity, or sterical
a
5
rangement of hemiaminals, three-component reaction of
hindrance) differing from DBU and K CO . As our continu-
2
3
14
lithiated alkoxyallenes with nitriles and carboxylic acids,3
f,6
ous studies on iodine-mediated reactions, we herein wish
to report these unexpected results on the stereoselective
oxidative dehydrogenation reaction for the synthesis of (Z)-
β-ketoenamides.
transition-metal-catalyzed amidation of α,β-unsaturated
7
carbonyl compounds, and rearrangement of β-tetrazolyl-
8
trans-benzalacetophenones. Nevertheless, these methods
often required rigorous conditions, such as exclusion of
moisture and air, high temperature, and utilization of
strong bases or transition metals. More importantly, stereo-
control of the double bond constitutes another issue to be
addressed, particularly in the synthesis of thermodynami-
cally disfavored (Z)-β-ketoenamides to meet special re-
quirements, such as total synthesis of natural products,9a
Initially, β-acylamino ketone 1a was chosen as the mod-
el substrate with the use of DABCO (3 equiv) as the base and
molecular iodine (1.2 equiv) as the oxidant to examine the
feasibility of oxidative dehydrogenation at 60 °C in toluene.
To our delight, the desired product 2a was isolated in 52%
yield, and only the Z-isomer was obtained in this transfor-
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Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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Synlett
H.-H. Chang et al.
Letter
Table 1 Dehydrogenation of 1a: Optimization of Reaction Conditionsa
a) Our previous work
I2 (10 mol%)
O
TBHP (3 equiv)
O
O
O
oxidant (1.2 equiv)
DABCO (3 equiv)
R1
R3
R3
R3
O
2 3
K CO (2 equiv)
O
HN
Me
O
HN
Me
N
R2
solvent, 60 °C
O
HN
R3
Ph
Ph
Ph
Ph
O
I2 (10 mol%)
TBHP (3 equiv)
1
a
2a
R1
R2
O
R1
DBU (2 equiv)
Yield (%)b
Entry
Oxidant
Solvent
N
b) This work
R2
O
I2 (1.2 equiv)
O
1
2
3
4
5
6
7
8
9
I
2
toluene
toluene
MeCN
MeOH
AcOH
EtOAc
THF
52
–c
DABCO (3 equiv)
R3
–
O
HN
O
HN
p-xylene
I
I
I
I
I
I
I
I
I
2
2
2
2
2
2
2
2
2
12
R1
R2
R1
R2
Z
12
Scheme 1 Different transfornations of β-acylamino ketones with the
–c
use of I and bases
2
47
48
25
48
58
60
38
19
10
mation (Table 1, entry 1). A control experiment showed
that no reaction occurred in the absence of iodine (Table 1,
entry 2). It was observed that solvent polarity had a signifi-
cant effect on the reaction efficiency (Table 1, entries 3–11).
For instance, the reaction in polar solvents such as nitrile,
acetate, methanol, and acetic acid gave inferior yields of (Z)-
β-ketoenamide 2a (Table 1, entries 3–6). When ether sol-
vents like THF or DME were used as the solvent, oxazoline
and oxazole derivatives were isolated as the major prod-
ucts. It was observed that benzene and benzene deriva-
tives such as chlorobenzene and p-xylene facilitated this
transformation, and the best result (60% yield) was ob-
tained when p-xylene was used as the solvent (Table 1, en-
tries 9–11). A simple survey of commonly used oxidants in-
dicated that molecular iodine was still the best of choice
DME
chlorobenzene
benzene
1
0
1
1
p-xylene
12
13
NIS
p-xylene
NBS
PIDA
p-xylene
14
p-xylene
a
Reaction conditions: 0.2 mmol of 1a, 0.24 mmol of oxidant, 0.6 mmol of
DABCO, in 2 mL of solvent at 60 °C for 4–6 h.
Isolated yield and only Z-isomer was observed.
16
b
c
Not detected.
the steric hindrance (2m vs. 2n). However, when the phenyl
ring was replaced by a methyl group, no desired β-ketoe-
namide 2q was detected. In addition, different N-protecting
groups of substrates were also tested for this dehydrogena-
tion reaction: for N-benzoyl substrate 1r, the dehydroge-
nated product 2q was only afforded in 35% yield, while 2,4-
diphenyl-5-benzoyl oxazoline generated via C–O bond for-
mation was isolated as the major product; two β-ketocar-
boxamides were also examined for this transformation and
resulted in high yields of the desired products (2s and 2t),
which could be readily transformed to polysubstituted py-
rimidines catalyzed by bases.3c
To understand the mechanism, a control experiment
was subsequently performed. N-Methyl-β-acetylamino ke-
tone 3 was prepared and tried for the present dehydrogena-
tion reaction, while the desired product 4 was not detected
(Scheme 3). This experiment indicated that the N–H bond
on the amide group was essential for the success of dehy-
drogenation. Based on the experimental result and litera-
ture reports,18 a plausible mechanism is proposed in
Scheme 4. After the deprotonation of β-acetylamino ketone
1a in the presence of DABCO, the nitrogen of the acetylami-
no group is firstly iodinated to form the N–I intermediate B,
which leads to the intramolecular α-iodination of the car-
bonyl group to produce intermediate C. Since the intramo-
(
Table 1, entries 12–14). For example, NIS decreased the
yield of 2a to 38%, while NBS and PIDA had much lower effi-
ciency and delivered the yield of 2a in 19% and 10%, respec-
tively.
With the optimal reaction conditions in hand (Table 1,
entry 11), we investigated the generality of the present ste-
1
7
reoselective synthesis of (Z)-β-ketoamides. As shown in
Scheme 2, various substrates bearing electron-withdrawing
or electron-donating groups on the aroyl moiety were well
tolerated to give the corresponding products 2b–e in mod-
erate to good yields (51–69%). Other aromatic systems such
as naphthyl, furyl, and thienyl groups were also proved to
be suitable for this transformation (2f–h). Furthermore, we
also varied different substituents on the aryl rings of β-
acetylamino ketones. For example, when the aryl ring was
replaced by the naphthyl ring, the desired product 2i was
obtained in 64% yield. It was noted that there were obvious
steric and electronic effects for the substituents on the aryl
moiety. For example, strong electron-withdrawing substit-
uents (such as the nitro group) on the aryl ring resulted in
better yields than that containing electron-donating groups
(
2o,p vs. 2j,k); the substrates bearing ortho-substituted
groups led to the lower yield of (Z)-β-ketoenamides due to
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Synlett
H.-H. Chang et al.
Letter
O
O
I2 (1.2 equiv)
DABCO (3 equiv)
R3
O
HN
R3
O
HN
p-xylene, 60 °C
R1
R2
R1
R2
z
1
2
O
O
O
O
O
O
HN
O
HN
O
HN
O
HN
O
HN
Ph
Ph
Ph
Ph
Ph
Br
Me
MeO
Cl
2a, 5 h, 60%
2b, 5h, 60%
2c, 6 h, 69%
2d, 8 h, 56%
2e, 7 h, 51%
O
O
O
O
O
O
HN
O
HN
O
HN
O
HN
O
HN
Ph
Ph
Ph
Ph
Ph
O
S
Me
2f, 6 h, 58%
2g, 5 h, 53%
2h, 5 h, 61%
2i, 7 h, 64%
2j, 8 h, 59%
O
O
O
O
O
O
HN
O
HN
O
HN
O
HN
Cl
O
HN
Ph
Ph
Ph
Ph
Ph
MeO
Br
Cl
NO2
2k, 12 h, 50%
2l, 6 h, 60%
2m, 6 h, 58%
2n, 6 h, 50%
2o, 6 h, 70%
O
O
O
O
O
O
HN
O
HN
O
HN
OEt
O
HN
OBn
NO2
O
HN
Ph
Ph
Ph
2r, 2 h, 35%a
Ph
Ph
2s, 2 h, 75%b
Ph
Ph
2t, 2 h, 78%b
Ph
Me
2p, 6 h, 78%
2q, 0
Scheme 2 Substrate scope for stereoselective dehydrogenation. Unless otherwise indicated, reactions were carried out with 0.2 mmol of 1a, 0.24
a
mmol of I , 0.6 mmol of DABCO, in 2 mL of p-xylene at 60 °C; the isolated yields and reaction times are shown. 2,4-Diphenyl-5-benzoyl oxazoline was
isolated in 60% yield. In 2 mL of THF.
2
b
lecular hydrogen bond fixes a predominant configuration of
intermediate C,7 elimination of HI promoted by DABCO
would give the desired (Z)-β-ketoenamide 2a.
ready availability of starting materials, broad substrate
scope, high stereoselectivity, and mild reaction conditions
make the present oxidative dehydrogenation attractive as a
synthetically feasible approach for the preparation of (Z)-β-
ketoenamides.
O
O
I2 (1.2 equiv)
DABCO (3 equiv)
Me
Me
O
N
Me
O
N
Me
X
p-xylene, 60 °C
6
h
Acknowledgment
We gratefully acknowledge the National Natural Science Foundation
of Shanxi Province (Nos. 2015021037 and 2015011023) and the proj-
ect supported by Special/Youth Foundation of Taiyuan University of
Technology (2014QN011).
3
4, not detected
Scheme 3 Control experiment for dehydrogenation
In summary, a mild and metal-free method for the de-
hydrogenation of β-acylamino ketones mediated by molec-
ular iodine has been developed. In each case, only the (Z)-β-
ketoenamide was obtained, and the high stereoselectivity
of dehydrogenation was mainly attributed to the intramo-
lecular H-bond interaction in the HI-elimination step. The
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561582.
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtogI
i
f
rm oaitn
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Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

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H.-H. Chang et al.
Letter
O
O
HN
Me
DABCO
O
O
I2
OH
O
H+
– I–
–
N
Me
N
I
Me
1a
A
B
O
O
H
N
O
HN
Me
DABCO
HI
I
Me
–
Z
H
O
2a
C
Scheme 4 Proposed mechanism for stereoslective dehydrogenation
References and Notes
(9) (a) Lin, S.; Yang, Z.-Q.; Kwok, K. H. B.; Koldobskiy, M.; Crews, C.
M.; Danyshefsky, S. J. J. Am. Chem. Soc. 2004, 126, 6347.
(1) (a) Huang, K.; Zhang, X.; Geng, H.; Li, S.-K.; Zhang, X. ACS Catal.
(b) Sugiura, M.; Kumahara, M.; Nakajima, M. Chem. Commun.
2012, 2, 1343. (b) Geng, H.; Huang, K.; Sun, T.; Li, W.; Zhang, X.;
2009, 3585.
Zhou, L.; Wu, W.; Zhang, X. J. Org. Chem. 2011, 76, 332. (c) Geng,
H.; Zhang, W.; Chen, J.; Hou, G.; Zhou, L.; Zou, Y.; Wu, W.;
Zhang, X. Angew. Chem. Int. Ed. 2009, 48, 6052.
(
10) For metal-catalyzed stereoselective synthesis of (Z)-enamides,
see ref. 6. For the formation of (Z)-enamides relying on base-
promoted rearrangement of propargylic hydroxylamines, see
ref. 3c. For the oxidation of α-amido esters to (Z)-enamides
using Dess–Martin periodinate, see: Nicolaou, K. C.; Mathison,
C. J. N. Angew. Chem. Int. Ed. 2005, 44, 5992.
(
2) (a) Davyt, D.; Entz, W.; Fernandez, R.; Mariezcurrena, R.;
Mombru, A. W.; Saldana, J.; Dominguez, L.; Coll, J.; Manta, E.
J. Nat. Prod. 1998, 61, 1560. (b) Yet, L. Chem. Rev. 2003, 103,
4283.
(11) Mphahlele, M. J. Molecules 2009, 14, 5308.
(
3) (a) Zheng, M.; Huang, L.; Huang, H.; Li, X.; Wu, W.; Jiang, H. Org.
Lett. 2014, 16, 5906. (b) James, C. A.; DeRoy, P.; Duplessis, M.;
Edwards, P. J.; Halmos, T.; Minville, J.; Morency, L.; Morin, S.;
Simoneau, B.; Tremblay, M.; Bethell, R.; Cordingley, M.; Duan, J.;
Lamorte, L.; Pelletier, A.; Rajotte, D.; Salois, P.; Tremblay, S.;
Sturino, C. F. Bioorg. Med. Chem. Lett. 2013, 23, 2781. (c) Gayon,
E.; Szymczyk, M.; Gérard, H.; Vrancken, E.; Campagne, J.-M.
J. Org. Chem. 2012, 77, 9205. (d) Wu, J.; Xu, W.; Yu, Z.-X.; Wang,
J. J. Am. Chem. Soc. 2015, 137, 9489. (e) Yamamoto, S.; Okamoto,
K.; Murakoso, M.; Kuninobu, Y.; Takai, K. Org. Lett. 2012, 14,
(
12) (a) Zuo, Z.; Xie, W.; Ma, D. J. Am. Chem. Soc. 2010, 132, 13226.
(b) Zuo, Z.; Ma, D. Angew. Chem. Int. Ed. 2011, 50, 12008. (c) Zi,
W.; Xie, W.; Ma, D. J. Am. Chem. Soc. 2012, 134, 9126. (d) Teng,
M.; Zi, W.; Ma, D. Angew. Chem. Int. Ed. 2014, 53, 1814.
(
13) For selected reviews, see: (a) Zhao, J.; Gao, W.; Chang, H.; Li, X.;
Liu, Q.; Wei, W. Chin. J. Org. Chem. 2014, 34, 1941. (b) Hu, F.;
Gao, W.; Chang, H.; Li, X.; Wei, W. Chin. J. Org. Chem. 2015, 35,
1848. (c) Finkbeiner, P.; Nachtsheim, B. J. Synthesis 2013, 45,
979. For selected examples, see: (d) Tian, X.; Song, L.; Li, E.;
Wang, Q.; Yu, W.; Chang, J. RSC Adv. 2015, 5, 62194.
3
(
6
182. (f) Dash, J.; Reissig, H.-U. Chem. Eur. J. 2009, 15, 6811.
g) Fürstner, A.; Weintritt, H.; Hupperts, A. J. Org. Chem. 1995,
0, 6637.
4) (a) Hommes, P.; Berlin, S.; Reissig, H.-U. Synthesis 2013, 3288.
b) Shabana, R.; Rasmussen, J. B.; Lawesson, S.-O. Tetrahedron
981, 37, 1819.
5) (a) Kang, Y.-W.; Cho, Y.-J.; Han, S.-J.; Jang, H.-Y. Org. Lett. 2016,
(
14) (a) Gao, W.-C.; Hu, F.; Huo, Y.-M.; Chang, H.-H.; Li, X.; Wei, W.-L.
Org. Lett. 2015, 17, 3914. (b) Gao, W.-C.; Zhao, J.-J.; Hu, F.;
Chang, H.-H.; Li, X.; Wei, W.-L. RSC Adv. 2015, 5, 25222. (c) Gao,
W.-C.; Zhao, J.-J.; Hu, F.; Chang, H.-H.; Li, X.; Wei, W.-L. RSC Adv.
(
(
(
(
1
2014, 4, 49329. (d) Gao, W.-C.; Jiang, S.; Wang, R.-L.; Zhang, C.
Chem. Commun. 2013, 49, 4890.
(
(
(
15) (a) Khan, A. T.; Parvin, T.; Choudhury, L. H. Tetrahedron 2007,
18, 272. (b) Kim, S. M.; Lee, D.; Hong, S. H. Org. Lett. 2014, 16,
63, 5593. (b) Xu, L.-W.; Xia, C.-G.; Hu, X.-X. Chem. Commun.
6168.
2003, 2570.
6) (a) Lechel, T.; Dash, J.; Eidamshaus, C.; Brüdgam, I.; Lentz, D.;
Reissig, H.-U. Org. Biomol. Chem. 2010, 8, 3007. (b) Bera, M. K.;
Reissig, H.-U. Synthesis 2010, 2129. (c) Eidamshaus, C.; Kumar,
R.; Bera, M. K.; Reissig, H.-U. Beilstein J. Org. Chem. 2011, 7, 962.
7) (a) Panda, N.; Jena, A. K.; Raghavender, M. ACS Catal. 2012, 2,
16) For the corresponding structures of oxazoline and oxazole
derivatives, see ref. 13a. For the screening of bases and results of
catalytic reaction studies, see Supporting Information.
17) General Procedure for Iodine-Mediated Oxidative Dehydro-
genation
(
539. (b) Lee, J. M.; Ahn, D.-S.; Jung, D. Y.; Lee, J.; Do, Y.; Kim, S.
A 10 mL oven-dried reaction vessel was charged with 1a (53
mg, 0.2 mmol), DABCO (67 mg, 0.6 mmol), and iodine (61 mg,
K.; Chang, S. J. Am. Chem. Soc. 2006, 128, 12954. (c) Gogoi, J.;
Gogoi, P.; Boruah, R. C. Eur. J. Org. Chem. 2014, 3483. (d) Panda,
N.; Mothkuri, R. J. Org. Chem. 2012, 77, 9407. (e) Ding, R.; Zhang,
Q.-C.; Xu, Y.-H.; Loh, T.-P. Chem. Commun. 2014, 50, 11661.
8) (a) Cherton, J.-C.; Desbene, P.-L.; Bazinet, M.; Lanson, M.;
Convert, O.; Basselier, J.-J. Can. J. Chem. 1985, 63, 86.
0.24 mmol) in p-xylene (2.0 mL). The resulting solution was
stirred at 60 °C for 5 h. After the reaction was complete, sat.
Na S O aq solution (10 mL) was added to quench the reaction,
2
2
3
(
and the mixture was extracted by EtOAc (3 × 10 mL). The
organic layer was separated and dried over anhydrous Na SO .
2
4
(b) Cherton, J.-C.; Bazinet, M.; Bolze, M.-M.; Lanson, M.;
After the removal of the solvent in vacuo, the residue was puri-
fied by flash column chromatography with PE–EtOAc (9:1) to
give 2a.
Desbene, P.-L. Can. J. Chem. 1985, 63, 2601.
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H.-H. Chang et al.
Letter
(
Z)-N-(3-Oxo-1,3-diphenylprop-1-en-1-yl)acetamide (2a)
(d, 2 H, J = 7.2 Hz), 7.57–7.41 (m, 8 H), 6.28 (s, 1 H), 4.13 (q, 2 H,
13
Yield 27 mg (60%); reaction time 5 h; white solid; mp 60–62 °C;
R = 0.35 (PE–EtOAc = 4:1). H NMR (400 MHz, CDCl ): δ = 12.27
J = 7.2 Hz), 1.26 (t, 3 H, J = 7.2 Hz). C NMR (100 MHz, CDCl ):
3
1
δ = 191.2, 157.0, 152.9, 138.7, 136.0, 132.5, 129.8, 128.6, 128.0,
f
3
(
7
s, 1 H), 7.98–7.95 (m, 2 H), 7.57 (tt, 1 H, J = 4.8, 0.8 Hz), 7.50–
127.8, 127.5, 103.5, 61.9, 14.2. ESI-HRMS: m/z calcd for
13
+
.46 (m, 4 H), 7.45–7.40 (m, 3 H), 6.33 (s, 1 H), 2.25 (s, 3 H).
C
C18H17NO Na [M + Na] : 318.1101; found: 318.1104.
3
NMR (100 MHz, CDCl ): δ = 191.7, 168.9, 156.3, 138.6, 136.2,
(19) (a) Minakata, S.; Morino, Y.; Oderaotoshi, Y.; Komatsu, M. Org.
Lett. 2006, 8, 3335. (b) Minakata, S.; Morino, Y.; Ide, T.;
Oderaotoshi, Y.; Komatsu, M. Chem. Commun. 2007, 3279.
3
1
32.7, 129.8, 128.7, 128.1, 127.8, 127.4, 104.8, 25.1. ESI-HRMS:
+
m/z calcd for C17H16NO [M + H] : 266.1176; found: 266.1179.
2
(18) (Z)-Ethyl (3-Oxo-1,3-diphenylprop-1-en-1-yl)carbamate (2s)
Yield 44 mg (75%); reaction time 2 h; yellow oil; R = 0.51 (PE–
f
1
EtOAc = 9:1). H NMR (400 MHz, CDCl ): δ = 11.95 (s, 1 H), 7.97
3
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E