Thieme Chemistry Journals Awardees - Where Are They Now? A Cascade Synthesis of 1,2,4-Triazin-3(2 H)-ones Using Nitrogen-Substituted Isocyanates

Article abstract of DOI:10.1055/s-0036-1588099

A cascade synthesis of 1,2,4-triazin-3(2H)-ones is reported from readily accessible α-amino ketones and phenyl carbazate as a masked N-isocyanate precursor. The mild protocol provides a simple route to products with substitution patterns which are difficult to form directly. This also presents the first N-isocyanate cascade requiring the use of acidic conditions, which accelerates formation of the hydrazone intermediate and the cyclization step. This cascade further highlights that high control can be achieved in reactions forming highly reactive N-isocyanate intermediates.

Full text of DOI:10.1055/s-0036-1588099

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
letter
A
M. A. Dahab et al.
Letter
Synlett
Thieme Chemistry Journals Awardees – Where Are They Now?
A Cascade Synthesis of 1,2,4-Triazin-3(2H)-ones Using Nitrogen-
Substituted Isocyanates
Mohammed A. Dahab‡ a
Joshua S. Derasp‡ b
André M.Beauchemin*b
O
O
C
N
H
N
O
H2N
N
N
H
OPh
citric acid
THF, rt
N
R1
R2
N
+
H
O
R3
N
H
N
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
Al-Azhar University, Cairo 11884, Egypt
b Centre for Catalysis Research and Innovation, Department of
Chemistry and Biomolecular Sciences, University of Ottawa,
10 Marie Curie, Ottawa, ON, K1N 6N5, Canada
andre.beauchemin@uottawa.ca
R1
R2
13 examples
up to 88% yield
R1
R2
R3
R3
rare N-isocyanates
‡ These authors contributed equally
Received: 25.10.2016
Accepted after revision: 26.10.2016
Published online: 10.11.2016
DOI: 10.1055/s-0036-1588099; Art ID: st-2016-r0628-l
Abstract A cascade synthesis of 1,2,4-triazin-3(2H)-ones is reported
from readily accessible α-amino ketones and phenyl carbazate as a
masked N-isocyanate precursor. The mild protocol provides a simple
route to products with substitution patterns which are difficult to form
directly. This also presents the first N-isocyanate cascade requiring the
use of acidic conditions, which accelerates formation of the hydrazone
intermediate and the cyclization step. This cascade further highlights
that high control can be achieved in reactions forming highly reactive
N-isocyanate intermediates.
Key words N-isocyanates, cascade reaction, 1,2,4-triazin-3(2H)-one,
α-amine ketone
André Beauchemin was born in Quebec city on August 6, 1974. He
obtained his BSc chemistry from the Université Laval, graduating in
1996 (working with Prof. J. Boukouvalas). He then studied at the Univer-
sité de Montréal under the guidance of Prof. André B. Charette, obtain-
ing his Ph.D. in 2001. His post-doctoral appointment was at Harvard
University, under the guidance of Prof. David A. Evans, working toward
the total synthesis of the marine natural product azaspiracid A. In Au-
gust 2004, André started as an assistant professor at the University of
Ottawa and was promoted to associate professor in 2010 and full pro-
fessor in 2015. From August to December 2013, André was a visiting
professor at ETH Zürich. His research interests include novel approaches
to bioactive nitrogen-containing molecules, ideally using inexpensive
reagents and catalysts. André has received the Thieme Chemistry Jour-
nals Award in 2006.
The development of new, efficient syntheses of nitro-
gen-containing heterocycles is important given their wide-
spread application within the pharmaceutical and agro-
chemical industry.1 1,2,4-Triazinones are important hetero-
cycles displaying a broad range of biological activities as a
result of their analogous structure to pyrimidine bases.2
1,2,4-Triazin-3(2H)-one derivatives have also attracted sig-
nificant interest, especially within the field of medicinal
chemistry.3 This interest can also be illustrated by the de-
velopment of pymetrozine, an antifeedant insecticide cur-
rently being employed in the United States and Europe.4 De-
spite the potential value of 1,2,4-triazin-3(2H)-ones, syn-
thetic approaches to this heterocycle have remained largely
rudimentary, typically requiring multistep syntheses or
forcing conditions.3e,5 Recently, Yu and coworkers reported
a novel cascade synthesis of this motif using phenyl carba-
zate and vinyl azides (Scheme 1).6 This method provided a
variety of 1,2,4-triazin-3(2H)-ones in good yield, but re-
quired the synthesis and thermolysis of vinyl azides. Inter-
estingly in this approach vinyl azides serve as precursors for
2H-azirines, which then react as primary α-aminoketone
equivalents. As a result of this, the reaction does not allow
access to products substituted at the 4-position. In contrast,
we were interested in a complementary approach involving
phenyl carbazate and suitable secondary α-amino ketones.
Given our previous work in heterocyclic synthesis using N-
isocyanates as reactive intermediates,7 we hypothesized
that a condensation (hydrazone formation)–cyclization ap-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

B
M. A. Dahab et al.
Letter
Synlett
Selected bioactive 1,2,4-triazin-3(2H)-ones
O
Me
O
O
NH
O
Ph
O
HN
N
NH
Ph
Ph
Ph
Me
N
N
N
N
Me
O
N
NH
Me
O
N
N
Me
Me
Me
HN
N
N
HN
N
N
H
HN
Me
O
pymetrozine
insecticide
HIV protease
inhibitor
calcium ion
channel blocker
phosphodiesterase
inhibitor
Yu's Work:
H
N
O
O
N
sealed vial
N3
R1
N
+
H2N
R2
NH
MeCN, 130 °C
N
OPh
R1
R1
R2
H
R2
2H-aziridine
This Work:
O
C
N
H
N
O
O
H
N
N
O
citric acid
THF, rt
+
N
H2N
R1
R2
R1
R2
N
N
OPh
H
H
R3
R3
N
R1
R2
13 examples
up to 88% yield
R3
N-isocyanate
Scheme 1 1,2,4-Triazin-3(2H)-ones and their syntheses using N-isocyanate cascade reactions
Table 1 Optimization of Reaction Conditionsa
proach could occur preferentially to the intermolecular re-
action of the secondary amine with the carbazate,7d and
provide the first example of a cascade in which the hydra-
zone N-isocyanate precursor is formed in situ. Herein, we
report such a N-isocyanate cascade, using secondary α-ami-
no ketones to form 1,2,4-triazin-3(2H)-ones using citric
acid as promoter.
H
N
O
O
O
rt
H
N
+
H2N
N
N
OPh
Ph
Ph
N
H
Ph
Ph
1a
2
3a
Entry Additive (equiv)
Solvent (M)
Time (h) Yield (%)b
As hinted above, all previous examples using hydra-
zones as N-isocyanate precursors for heterocyclic synthesis
involved the preparation of the substrate in a prior step us-
ing condensation chemistry. However, such condensations
can be difficult to achieve, especially with hindered ketones
as substrates.8 Additional difficulties present with this sys-
tem are that both N-isocyanates and α-amino ketones could
form homodimers.9,10 Conceptually, we hypothesized that
catalysis could allow for controlled reactivity, for example,
by base-catalyzed intermolecular addition of the secondary
amine on phenyl carbazate (followed by intramolecular
condensation), or by acid-catalyzed condensation, followed
by intramolecular cyclization on the N-isocyanate interme-
diate. With this in mind we initiated our investigation prob-
ing conditions to form the desired 1,2,4-triazin-3(2H)-one
using phenyl carbazate and 2-anilinoacetophenone as mod-
el system (Table 1). This particular α-amino ketone was
chosen due to its ease of access as well as its reduced ten-
dency to dimerize.
1
DBU (0.2)
THF (0.3)
THF (0.3)
THF (0.3)
THF (0.5)
MeCN (0.5)
PhCF3 (0. 5)
MeOH (0.5)
THF (0.1)
THF (1.0)
THF (1.0)
16
16
16
12
12
12
12
12
12
12
degradation
2c
3c
4
none
no reaction
Et3N (0.2)
degradation
citric acid (1.0)
citric acid (1.0)
citric acid (1.0)
citric acid (1.0)
citric acid (1.0)
citric acid (1.0)
none
73
5
60
6
11
7
62
8
27
9
73 (74)d
no reaction
10
a Reaction conditions: phenyl carbazate (2, 1.0 equiv), 1a (1.05 equiv), and
citric acid (1 equiv) in THF (0.5 M) stirred at r.t.
b 1H NMR yield based on 1,3,5 trimethoxybenzene as internal standard.
c Reflux.
d Isolated yield.
was a competent catalyst for simple substitution reactions
of phenyl carbazate.7i Unfortunately, these conditions did
not provide the desired semicarbazide or product but in-
stead resulted in the degradation of the α-amino ketone
and dimerization of the carbazate (Table 1, entry 1). Ther-
Initially, basic conditions were tested using 1,8-diazabi-
cycloundec-7-ene (DBU). Previously, we reported that DBU
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

C
M. A. Dahab et al.
Letter
Synlett
mal conditions were also tested yielding no reaction (entry
2), and in the presence of a mild base produced the same
results observed with DBU ( entry 3). These results suggest-
ed that the nucleophilicity of the aniline is not sufficient to
outcompete phenyl carbazate dimerization and led to a sur-
vey of conditions which would promote the condensation
reaction. This proved fruitful with stoichiometric amounts
of citric acid11 providing the desired product in 73% NMR
yield after stirring for 12 hours at room temperature (entry
4). A solvent scan was performed showing that THF was the
optimal solvent for this cascade reaction (entries 5–7). The
concentration of the reaction was observed to have signifi-
cant effect on the overall reaction with a 0.1 M reaction re-
sulting in a 27% yield (entry 8) while increasing the reaction
concentration from 0.5 to 1 M resulted in no change in yield
(entry 9). A control reaction performed in the absence of
citric acid stressed its importance in this cascade reaction
with neither the condensation product (hydrazone) or de-
sired 1,2,4-triazin-3(2H)-one detected by NMR spectrosco-
py (entry 10). With optimized conditions in hand, we pro-
ceeded to probe the applicability of this reaction (Scheme 2).
The substituent effect on the aniline moiety was evalu-
ated first. Electron-donating substituents on the aniline
ring were well tolerated under the reaction conditions with
p-methyl (3b), 3,5-dimethyl (3c), and p-methoxy (3d) all
providing the 1,2,4-triazin-3(2H)-one in good yields. Elec-
tron-withdrawing groups also afforded the desired product,
as illustrated with p-fluoro-substituted product 3e, and
even the strongly electron-withdrawing ester yielded prod-
uct although heating was necessary to achieve cyclization
(3f). We then surveyed the reactivity of a variety of differ-
ent ketone substituents on the α-amino ketone. Both elec-
tron-rich (3g) and electron-poor (3h) aromatics provided
the product in moderate to good yield. An alkyl substituent
was also a competent reaction partner under the reaction
conditions, despite the increased steric bulk (3i). Finally,
the impact of substitution at the α position was probed. As
expected the presence of a methyl group at this position
had a substantial effect on the reaction: heating was re-
quired to achieve efficient cyclization to form product 3j in
good yield. Cyclic derivatives also proved amenable to the
cascade although these were found to be low-yielding (3k
and 3l). Overall, this methodology provides mild access to
an array of 1,2,4-triazin-3(2H)-ones.
OPh
O
NH
We next sought to probe applicability of this procedure
to the large scale synthesis of 1,2,4-triazin-3(2H)-one 3a.
The reaction was performed on a 1.05 g scale using sub-
strate 1a under standard reaction conditions (Scheme 3).
This led to an 88% isolated yield of the desired product, a
crystalline product that could also be obtained in an unop-
timized 60% yield by crystallization.12
O
C
N
O
N
OPh
H
N
NH2
2
O
N
NH
citric acid
– PhOH
+ PhOH
+
N
N
H
N
R1
R2
O
H
THF, rt
H
N
R1
R2
R1
R2
R3
N
R1
R2
R3
3a–l
R3
R3
1b–l
H
H
N
N
O
O
H
N
N
N
O
H
O
N
N
N
Me
O
N
O
citric acid
THF
Ph
Ph
H
N
+
H2N
N
N
N
H
OPh
Ph
Ph
Ph
Ph
N
Me
Ph
Ph
3a
3b
3c
1a
2
3a
88% (gram scale)
76% (12 h)
77% (12 h)
Me
1.05 g
88%
H
H
N
O
H
N
O
N
N
O
N
Scheme 3 Gram-scale synthesis
N
N
N
Ph
N
Ph
Ph
F
3e
3f
55%a
3d
60% (12 h)
CO2Et
The applicability of this protocol was then explored
with a primary α-aminoketone (Scheme 4), using commer-
cially available 2-aminoacetophenone hydrochloride as the
test substrate. This substrate was not amenable to room-
temperature reactivity, in fact, reflux in ethanol in the pres-
ence of excess of carbazate 2 was required to obtain a high
yield of 3m. This preliminary data suggests the scope of this
protocol could be expanded to include other α-aminoke-
tones.
OMe
O
67% (12 h)
H
H
N
N
O
H
N
N
N
O
N
N
N
Ph
NC
Ph
N
tBu
Ph
MeO
3g
3h
3i
53% (12 h)
66% (16 h)
58% (16 h)
H
N
H
H
N
O
N
O
O
N
N
N
N
N
N
Ph
Ph
Ph
Ph
H
O
Me
3j
61%b
O
N
O
EtOH
N
+
H2N
3k
22%c
3l
NH3Cl
N
OPh
80 °C, 24 h
32% (16 h)
Ph
NH
H
Ph
1m
2
3m
77%
Scheme 2 Scope of cascade reaction forming 1,2,4-triazin-3(2H)-ones.
Reagents and conditions: phenyl carbazate (2, 1.0 equiv), 1b–l (1.05
equiv), and citric acid (1.0 equiv) in THF (1.0 M) stirred at r.t. a Stirred at
r.t. for 7 h, followed by reflux for 20 h. b Stirred at r.t. for 12 h, followed
by reflux for 24 h. c Stirred at r.t. for 12 h, followed by reflux for 20 h.
Scheme 4 Reaction of a primary α-aminoketone
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

D
M. A. Dahab et al.
Letter
Synlett
Finally, we turned our attention to the mechanism of
this cascade reaction. In order to support our proposed
mechanism, that is, intermolecular condensation followed
N-isocyanate formation and intramolecular cyclization, we
sought to isolate the α-aminocarbazone intermediate. Sub-
strate 1a was submitted to the standard reaction condi-
tions, and the reaction was interrupted after one hour. This
resulted in the formation and isolation of both the Z (4a)
and the E (4b) isomer of the desired α-aminocarbazone
(Scheme 5, top). Both of these intermediates were submit-
ted to standard reaction conditions to probe their capacity
to form product. Gratifyingly, both isomers were observed
to form the desired 1,2,4-triazin-3(2H)-one, albeit in mod-
est yield, supporting their role as intermediates in the reac-
tion cascade (Scheme 5, bottom). Moreover, this demon-
strates the ease with which E/Z isomerization occurs under
the reaction conditions, as reaction monitoring indicated
that both reactions looked identical by TLC shortly after the
addition of citric acid.
In conclusion, we have developed a new 1,2,4-triazin-
3(2H)-one synthesis through a controlled cascade reaction
between a masked N-isocyanate precursor and α-amino ke-
tones. This strategy provides access to various 1,2,4-triazin-
3(2H)-ones under mild reaction conditions. Moreover, this
work contains the first evidence of an acid-promoted N-iso-
cyanate formation. This provides a novel strategy in N-iso-
cyanate cascade reactions which should be applicable in
the context of other heterocyclic syntheses. This also pres-
ents the first cascade reaction where the masked N-isocya-
nate precursor is formed in situ. The development of other
cascade reactions involving rare heteroatom-substituted
isocyanates is ongoing and will be reported in due course.
Acknowledgment
We thank the University of Ottawa and NSERC for financial support.
M.A.D. thanks the Egyptian Ministry of High Education for a scholar-
ship, and J.S.D. thanks OGS for a scholarship.
O
N
OPh PhO
O
N
O
Supporting Information
O
NH
HN
Ph
H
citric acid
THF, 1 h
+
H2N
N
N
OPh
H
H
Ph
Ph
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588099.
H
N
N
Ph
Ph
Ph
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
1a
2
4a
21%
4b
9%
O
N
OPh
PhO
O
N
References and Notes
H
N
O
citric acid
THF, 6 h
H
N
NH
HN
Ph
4a 37%
4b 47%
or
Ph
(1) (a) Trost, B. M. Science 1983, 219, 245. (b) Vitaku, E.; Smith, D.
T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257.
N
H
N
Ph
Ph
N
Ph
Ph
3a
(2) For selected publications on 1,2,4-triazinone bioactivity, see:
(a) Abdel-Halim, A. M.; el-Gendy, Z.; Abdel-Rahman, R. M. Phar-
mazie 1995, 50, 726. (b) Bhatia, P. A.; Brooks, C. D. W.; Basha, A.;
Ratajczyk, J. D.; Gunn, B. P.; Bouska, J. B.; Lanni, C.; Young, P. R.;
Bell, R. L.; Carter, G. W. J. Med. Chem. 1996, 39, 3938.
(c) Schmitz, W. D.; Brenner, A. B.; Bronson, J. J.; Ditta, J. L.;
Griffin, C. R.; Li, Y.-W.; Lodge, N. J.; Molski, T. F.; Olson, R. E.;
Zhuo, X.; Macor, J. E. Bioorg. Med. Chem. Lett. 2010, 20, 3579.
(d) Sztanke, K.; Tuzimski, T.; Sztanke, M.; Rzymowska, J.;
Pasternak, K. Bioorg. Med. Chem. 2011, 19, 5103. (e) Saad, H. A.;
Moustafa, A. H. Molecules 2011, 16, 5682.
(3) For selected publications on 1,2,4-triazin-3(2H)-one bioactivity,
see: (a) Kristinsson, H. US 4931439, 1990. (b) Martin, M.;
Nadler, G.; Zimmermann, R. US 4933336, 1990. (c) Coates, W. J.
US 4906628, 1990. (d) Betebenner, D. A.; Chen, X.; Condon, S. L.;
Cooper, A. J.; Dickman, D. A.; Hannick, S. M.; Herrin, T. R.;
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D. W.; Oliver, P. A.; Patel, K. M.; Plata, D. J.; Sham, H. L.; Stengel,
P. J.; Stoner, E. J.; Tien, J.-H. J. EP1 170289A2, 2002. (e) Nagato,
S.; Kawano, K.; Ito, K.; Norimine, Y.; Ueno, K.; Hanada, T.;
Amino, H.; Ogo, M.; Hatakeyama, S.; Ueno, M.; Groom, A. J.;
Rivers, L.; Smith, T. US 2003225081, 2003. (f) Grauert, M.;
Bakker, R.; Breitfelder, S.; Buettner, F.; Eickelmann, P.; Fox, T.;
Grundl, M.; Lehmann-Lintz, T.; Rist, W. WO 2011138427, 2011.
(g) Oi, N.; Tokunaga, M.; Suzuki, M.; Nagai, Y.; Nakatani, Y.;
Yamamoto, N.; Maeda, J.; Minamimoto, T.; Zhang, M.-R.;
Suhara, T.; Higuchi, M. J. Med. Chem. 2015, 58, 8444. (h) Yang, Y.;
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391. (i) Liang, C.; Pan, S.; Yang, S.; Wang, J. WO 2016023877,
2016.
4a
4b
Scheme 5 Isolation of intermediates and control experiments
The effect of citric acid on the cyclization was also in-
vestigated (Scheme 6). It was initially assumed that acid
only benefited the initial condensation given the lack of for-
mation of 4a and 4b in the absence of acid. Moreover, given
our previous work using base catalysis to achieve N-isocya-
nate formation, it would be possible that acid impedes N-
isocyanate formation. Unexpectedly, submitting both 4a
and 4b to the standard reaction conditions without citric
acid yielded starting material with no detectable product
formed. To our knowledge, this represents the first evi-
dence of acid-promoted cyclization of a blocked (masked)
N-isocyanate.
O
N
OPh PhO
or
O
N
H
N
O
no acid
N
NH
HN
Ph
4a: no reaction
4b: no reaction
N
H
H
THF, 6 h
Ph
Ph
N
N
Ph
Ph
Ph
3a
4a
4b
Scheme 6 Control experiments without acid
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

E
M. A. Dahab et al.
Letter
Synlett
(4) European Food Safety Authority EFSA Journal 2014, 12, 3817.
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(c) Polonovski, M.; Pesson, M.; Rajzman, P. C. R. Hebd. Seances
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Ueno, K.; Hanada, T.; Amino, H.; Ogo, M.; Hatakeyama, S.; Ueno,
M.; Groom, A. J.; Rivers, L.; Smith, T. WO 200222587, 2001.
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(r) Verardo, G.; Geatti, P.; Merli, M.; Strazzolini, P. Eur. J. Org.
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(12) Recrystallization resulted in a 60% yield of the desired com-
pound while the remaining 28% was obtained through column
purification. See Supporting Information for details.
(13) General Procedure for the Cascade Reaction
In a dry microwave vial equipped with a stir bar, the α-amino
ketone (1.05 equiv) was added to phenyl carbazate (1.0 equiv)
and citric acid (1.0 equiv). The vial was then sealed and purged
with argon followed by the addition of purified THF (1.0 M). The
resulting solution was left stirring at r.t. for 12–16 h. The reac-
tion mixture was concentrated under reduced pressure, diluted
with a sat. NaHCO3 solution (20 mL), and extracted with EtOAc
(3 × 10 mL). The organic layers were combined, dried over
NaSO4, filtered, and concentrated under reduced pressure. The
crude products were purified by column chromatography or
through recrystallization in MeOH.
(14) 4,6-Diphenyl-4,5-dihydro-1,2,4-triazin-3(2H)-one (3a)
Synthesized according to the general procedure using α-amino
ketone 1a (0.133 g, 0.630 mmol), phenyl carbazate (0.0912 g,
0.600 mmol), and citric acid (0.115 g, 0.600 mmol), then puri-
fied THF (0.6 mL, 1.0 M) was added under argon. The resulting
solution was left stirring at r.t. for 12 h. The title compound was
purified by column chromatography (5% EtOAc–CH2Cl2) to yield
a white solid (0.186 g, 74%). TLC: Rf = 0.23 in 5% EtOAc–CH2Cl2.
1H NMR (400 MHz, CDCl3): δ = 8.09 (s, 1 H), 7.68 (ddd, J = 4.4,
2.5, 1.4 Hz, 2 H), 7.44 (t, J = 2.7 Hz, 2 H), 7.42 (dd, J = 2.7, 1.6 Hz,
4 H), 7.40 (d, J = 3.1 Hz, 1 H), 7.31–7.26 (m, 1 H), 4.74 (s, 2 H).
13C NMR (101 MHz, CDCl3): δ = 151.5, 143.3, 140.4, 133.4, 130.0,
129.2, 128.8, 126.6, 125.3, 124.5, 47.7. IR (ATR diamond): 3216,
3097, 1662, 1625, 1593, 1195, 772 cm–1. HRMS (EI): m/z calcd
for C15H13N3O [M]+: 251.1053; found: 251.1056.
(15) Procedure for the Primary α-Amino Ketone: 6-Phenyl-4,5-
dihydro-1,2,4-triazin-3(2H)-one (3m)
In a dry microwave vial equipped with a stir bar, 2-aminoace-
tophenone hydrochloride (0.103 g, 0.600 mmol) was added to a
solution of phenyl carbazate (0.273 g, 1.80 mmol) in EtOH (1.20
mL, 0.50 M) and refluxed under argon for 24 h. The reaction
mixture was concentrated under reduced pressure, and dry
loaded onto silica gel. The title compound was purified by
column chromatography (100% EtOAc to 5% MeOH–CH2Cl2) to
yield a white solid (0.0813 g, 77%). TLC: Rf = 0.27 in 5% EtOAc–
1
CH2Cl2. H NMR (400 MHz, DMSO-d6): δ = 9.90 (d, J = 1.8 Hz, 1
H), 7.63–7.61 (m, 2 H), 7.40–7.34 (m, 3 H), 7.22 (s, 1 H), 4.60 (d,
J = 1.8 Hz, 2 H). 13C NMR (101 MHz, DMSO-d6): δ = 152.4, 141.9,
134.6, 129.7, 129.0, 125.5, 40.5.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E