Copper-Catalyzed Enaminone C(sp2)-N Bond Phosphonation for Stereoselective Synthesis of Alkenylphosphonates

Article abstract of DOI:10.1021/acs.joc.1c00862

A direct enaminone C-N bond coupling functionalization that generates a new C-P bond using dialkyl phosphonate for the efficient and stereoselective synthesis of (E)-alkenylphosphonates is reported. The reactions toward target products proceed well with a broad scope, disclosing a valuable new synthetic application of enaminones by the interesting C(sp2)-N bond elaboration.

Full text of DOI:10.1021/acs.joc.1c00862

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Note
2
Copper-Catalyzed Enaminone C(sp )−N Bond Phosphonation for
Stereoselective Synthesis of Alkenylphosphonates
Ting Liu, Li Wei, Baoli Zhao, Yunyun Liu,* and Jie-Ping Wan*
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sı Supporting Information
ABSTRACT: A direct enaminone C−N bond coupling function-
alization that generates a new C−P bond using dialkyl
phosphonate for the efficient and stereoselective synthesis of
(E)-alkenylphosphonates is reported. The reactions toward target
products proceed well with a broad scope, disclosing a valuable
new synthetic application of enaminones by the interesting
2
C(sp )−N bond elaboration.
n recent decades, phosphonates and their derivatives have
these reported works, developing new methods allowing the
synthesis of such enone-functionalized phosphonates with high
stereoselectivity and broad synthetic scope by a one-step
operation using readily available substrates is yet highly
desirable.
I
received increasing attention for their significant applica-
1
2
tions in drug discovery, synthetic organic chemistry,
3
4
materials science, and catalysis. Particularly, alkenylphos-
phorous compounds have found valuable applications as
5
additives or flame retardants in polymer science, as key
On the other hand, as one of the most ubiquitously available
chemical bonds in natural and synthesized molecules, the C−N
bond transformation bears huge space in developing novel and
practical new synthetic tactics. However, compared to the
splendid success in equivalent C−H and C−C bond activation
or functionalization chemistry, the research on C−N bond
building blocks in the synthesis of extensively functionalized
6
7
olefins, as well as (hetero)cyclic scaffolds. More notably,
some alkenylphosphonates and related polymers have been
identified to possess important biological activities such as
8a
antiatherogenic activity, cysteine protease inhibitory activi-
ty, etc. The Hirao reaction using Pd-catalyzed coupling of
aryl/vinyl halides and phosphonates could be used for the
8
b
17
activation or functionalization is still in its infancy. In this
context, searching for new synthetic protocols by coupling
stable C−N bonds is of enormous significance for the current
synthetic science.
9
synthesis of alkenylphosphonates. In addition, a few synthetic
tactics, such as Heck coupling of readily available vinyl
1
0
phosphonates, alkenyl C−H/C−H coupling of two vinyl
Enaminones are stable enamine compounds that show a
highly broad application in a massive number of synthetic
11
phosphine oxides, cross-coupling of P(O)H substrates with
1
2
13
18
alkenyl halides, the hydrophosphonylation of alkynes, and
the decarboxylative coupling of alkenyl acids with H-
reactions. The extensive investigation by our and other
research groups disclosed many featured transformation
models on enaminone and their application in the designation
of practical synthetic methods. For example, the alkenyl C−H
1
4
phosphonates have been developed for the synthesis of
alkenylphosphonates. However, the reliance on noble metal
catalysis or the requirement of prior prepared vinyl
phosphonates as starting materials remains as challenges in
alkenylphosphonates synthesis. Particularly, the insufficient
types of synthetic methods have imposed the restriction
accordingly in the diversity of the synthesized alkenylphosph-
onate products. The enone-functionalized phosphonates, for
example, are presently accessible with only rather scarce
methods. One available method for the synthesis of enone
phosphonates is the frustrated Lewis pair-catalyzed addition of
the P−H bond in dialkyl phosphonates to ynones, which
provided the synthesis of alkenylphosphonates with up to 20:1
19
20
functionalization, the CC double bond functionalization,
the CC double bond participated aromatic ring con-
22
21
struction, as well as many other novel reactions involving
multiple bond transformation in enaminones have been
extensively investigated, and notable success has been gained
accordingly over the recent years. The direct coupling
transformation on the CN bond of enaminones forming
other types of new chemical bonds, however, is yet quite
Received: April 14, 2021
Published: June 30, 2021
15
Z/E stereoselectivity. On the other hand, Chen and co-
workers synthesized several E-configurated enone-based
phosphonates via the condensation and subsequent C−P
bond cleavage of α-oxo aldehydes and methylene-bridged bis-
16
phosphonates via the treatment of NaH at 0 °C. In spite of
©
2021 American Chemical Society
https://doi.org/10.1021/acs.joc.1c00862
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Note
underdeveloped. In continuous to our research interest in
exploring divergent organic transformation on enaminones and
their synthetic application, we report herein the first CN
bond coupling for direct new CP bond formation by
employing dialkyl phosphonates as coupling partners with
copper catalysis.
To start the investigation, the reaction of enaminone 1a and
diethyl phosphonate 2a was conducted under a variety of
different conditions (Table 1). First, a series of Cu(I), Cu(II),
higher and lower temperature provided the target product with
lower yield (entries 20 and 21, Table 1). The N,N-diethyl and
N,N-dibenzyl substituted enaminones could also take part in
the transformation, providing 3a, but with a slightly lower yield
(entries 22 and 23, Table 1). When an NH-enaminone
resulting from the transamination of 2a and aniline was used
to react with 2a, the product 3a was not observed. Analysis of
the crude product from this reaction under optimal conditions
indicated that a small amount of Z-isomeric product of 3a was
also formed (see Supporting Information).
In the work of investigating the synthetic scope, an array of
different enaminones 1 were first employed to react with
phosphonate 2a under the optimized conditions. A broad
substrate tolerance, as shown in Scheme 1, was identified with
23
a
Table 1. Typical Data on Condition Optimization
b
Scheme 1. Scope of Enaminones for the Diethyl
Alkenylphosphonates Synthesis
entry
catalyst
solvent
toluene
additive
T (°C) yield (%)
,
a b
1
2
3
4
5
6
7
8
9
Cu(OTf)2
CuBr2
CuBr
CuCl
FeCl3
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
70
90
80
80
50
36
25
37
29
40
30
33
55
75
61
56
59
36
53
75
47
56
64
32
71
65
60
toluene
toluene
toluene
toluene
DMSO
DMF
1,4-dioxane
CH CN
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
CH CN
p-TSA
AcOH
TFA
3
CH CN
3
CH CN
3
CH CN
Et N
3
3
CH CN
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA
p-TSA
3
c
d
e
f
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
CH CN
3
CH CN
3
CH CN
3
CH CN
3
g
CH CN
3
CH CN
3
CH CN
3
h
i
CH CN
3
CH CN
3
a
b
a
Isolated yields were reported. Although all of the products were
General conditions: 1a (0.2 mmol, R = Me), 2a (0.4 mmol), catalyst
0.04 mmol), additive (0.4 mmol), and solvent (2.0 mL), stirred at 80
C for 12 h under an air atmosphere. Yield of isolated product based
on 1a. With 0.2 mmol 2a. With 0.6 mmol 2a, H NMR on the crude
product indicated that E- and Z-isomers were formed in the ratio of
isolated as pure E-isomers, a small amount of the Z-isomeric
compound was observed in all of the reactions herein before isolation.
(
°
b
c
d
1
e
f
g
≈
5:1. With 0.2 mmol p-TSA. With 0.03 mmol Cu(OTf)2. With
the reactions of enaminones. The conventional enaminones
bearing alkyl-, alkoxyl-, halogen-, trifluoromethyl-, and cyano-
functionalized phenyl structure took part in the synthesis to
provide corresponding alkenylphosphonates with moderate to
good yields (3a−3m). Furthermore, the sensitive amino
substituent (3n) and disubstituted phenyl-based enaminones
(3o and 3p) were also well tolerated. When α-naphthyl and β-
naphthyl functionalized enaminones were utilized, the
products 3q and 3r were provided with 46% and 50% yield,
respectively. Notably, heteroaryl such as furyl- and thiophenyl-
derived enaminones could also smoothly be used for the
synthesis of equivalent products to indicate the expanded
application scope of the method (3s and 3t). However,
aliphatic ketone-derived and pyrrole/pyridine-functionalized
enaminones did not show the target transformation under the
present conditions (Scheme 1).
h
i
0
.05 mmol Cu(OTf)2. R = Et. R = benzyl.
and Fe(III) salts were screened, and we were delighted to find
that the Cu(OTf) catalysis gave among the best result of 50%
2
yield of product 3a (entries 1−5, Table 1). Later, the reaction
was also conducted in different organic media, including
DMSO, DMF, 1,4-dioxane, and MeCN, wherein MeCN
displayed a better effect on the product formation than any
other candidates (entries 6−9, Table 1). In subsequent efforts,
several acids and base additives were individually employed,
and p-toluenesulfonic acid (p-TSA) was found to be capable of
significantly enhancing the product yield (entries 10−13, Table
1
). A control entry without using a copper catalyst provided 3a
with an evidently inferior result (entry 14, Table 1). Later on,
the loading of substrate 2a (entries 15 and 16, Table 1), p-TSA
(
entry 17, Table 1), and Cu(OTf) catalyst (entries 18 and 19,
In a further study, the reactions employing different alkyl
phosphonates 2 were also conducted. Delightfully, phospho-
nates with alkyls of different structural features, including
2
Table 1) was also optimized, respectively. However, no further
improved result was afforded. Finally, the reaction at both
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methyl (3u−3w, Scheme 2), i-propyl (3x, Scheme 2), butyl
sulfonyl hydrazine 6 (Scheme 3D). These results strongly
supported that the enone-functionalized phosphonate products
are highly useful synthetic precursors.
(
3y, Scheme 2), and even benzyl (3z, Scheme 2), were
Scheme 2. Scope of Alkyl Phosphonate for the Synthesis of
Alkenylphosphonates
In order to gain information on the possible reaction
mechanism, a series of control experiments were executed.
First, the standard model reaction was conducted in the
presence of TEMPO and BHT, respectively. No evident
inhibition of these free radical scavengers to the reaction was
observed (eqs 1 and 2), suggesting that the reaction did not
proceed via a free radical process. In addition, employing
,
a b
CD COD as an additive in the reaction led to the formation of
3
deuterium-labeled product 3a-d in equal yield with 3a (eq 3),
proving that proton release and capture had taken place during
the reaction.
a
b
Isolated yields were reported. Although all of the products were
isolated as pure E-isomers, a small amount of Z-isomeric compound
was observed in all of the reactions herein before isolation.
practically transformed into correspondingly diverse alkenyl-
phosphonate products without encountering the impact of the
alkyl property. In addition, the diphenyl phosphonate and
diphenylphosphine oxide were utilized to react with 1a under
the standard conditions, respectively. But the target trans-
formation was not observed in both entries.
Later, to examine the power of large-scale synthesis of this
method, the model reaction was conducted on a 3 mmol scale.
It was found that a 66% yield of 3a was afforded, confirming
the high application potential of the present method in a large
amount of alkenylphosphonate synthesis (Scheme 3A).
Following the information given by these typical control
experiments, the possible mechanism for this reaction is
proposed (Scheme 4). First, the Cu(II) salt couples
Scheme 3. Scale-up Synthesis and Application of the
Alkenylphosphonate Product
Scheme 4. Proposed Reaction Mechanism
enaminone to form complex A via configuration reversion
under the driving force of the Cu−O and Cu−N
24
coordination. The protonation based on its tautomeric
form B is thus facilitated in the presence of Brønsted acid to
form iminium cationic intermediate C by releasing Cu(II). It
should be noted that the acid catalysis without configuration
inversion could also promote the target transformation as
observed in Table 1, albeit with lower efficiency. The addition
of diethyl phosphonate yields another intermediate D. The
adduct E resulting from the incorporation of proton to D then
affords the target product 3 by undergoing elimination of
dimethyl amine.
Moreover, the synthetic derivation on 3a was executed to
illustrate the potential application of the synthesized products.
Typically, the hydroamination on the double CC bond of
3
a, provided aminoalkyl functionalized phosphonate 4
(Scheme 3B). The hydrothiolation affording alkylthiolated
phosphonate 5 (confirmed by NOESY NMR analysis, see
Supporting Information) was achieved via a facile operation
In conclusion, we have realized herein the first example on
C−P bond formation by the coupling functionalization of the
C−N bond in tertiary enaminones in the catalytic system of
(Scheme 3C). In addition, the reaction of 3a with phenyl-
sulfonyl hydrazine was also efficiently run to access useful
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Note
combined Cu(OTf) and p-TSA. The method displays a
MHz, CDCl
) δ 192.9 (d, JC−P = 22.0 Hz), 143.3 (d, JC−P = 6.0 Hz),
3
2
1
38.7, 136.5, 131.9 (d, JC−P = 5.0 Hz), 131.7, 129.9, 129.2, 125.7, 62.5
satisfactory application scope to both components and, thus,
offers a highly useful new option for the synthesis enone-
functionalized phosphonates to complement those scarcely
available known methods. More notably, the current results
disclose new synthetic potential of the enaminones by direct
functionalization of the C−N bond to construct new chemical
bond.
3
1
(d, JC−P = 6.0 Hz), 20.8, 16.4 (d, JC−P = 6.0 Hz); P NMR (162
+
MHz, CDCl ) δ 15.8; ESI-HRMS calcd for C H O PNa [M + Na]
3
14 19
4
3
05.0913, found 305.0911.
Diethyl (E)-(3-(4-Methoxyphenyl)-3-oxoprop-1-en-1-yl)-
phosphonate (3e): eluent, v /v = 2:1; colorless oil (44 mg,
7
PET EA
1
4% yield); H NMR (400 MHz, CDCl ) δ 8.03 (d, J = 8.8 Hz, 2H),
3
7.85 (t, J = 21.0 Hz, 1H), 6.98 (q, 3H), 4.17 (q, 4H), 3.90 (s, 3H),
1
3
1
1.37 (t, J = 7.0 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 186.6
3
d, JC−P = 22.0 Hz), 164.3, 140.8, 131.5, 129.3, 128.5, 114.2, 62.7,
EXPERIMENTAL SECTION
3
1
■
5.6, 16.4 (d, JC−P = 6.0 Hz); P NMR (162 MHz, CDCl ) δ 17.4;
3
+
General Experimental Information. All experiments were
carried out under an air atmosphere. The enaminones were
synthesized following the literature process. Other chemicals and
solvents used in the experiments were obtained from commercial
sources and used directly without further treatment. The H, C, and
1
4
19
5
21.0861.
2
5
Dethyl (E)-(3-(3-Methoxyphenyl)-3-oxoprop-1-en-1-yl)-
PET EA
1
13
1
3
31
P NMR spectra were recorded in a 400 MHz apparatus in CDCl .
3
1
31
13
The frequencies for H NMR, P NMR, and C NMR are 400, 162,
and 100 MHz, respectively. The chemical shifts were reported in ppm
with TMS as an internal standard. Melting points were tested in an X-
1
3
1
3
4
A instrument without correcting temperature, and the HRMS data
for all new products were obtained under an ESI model in a mass
spectrometer equipped with a TOF analyzer.
P NMR (162 MHz, CDCl ) δ 16.4; ESI-HRMS calcd for
3
+
Diethyl (E)-(3-(4-Fluorophenyl)-3-oxoprop-1-en-1-yl)-
Genral Procedure for the Synthesis Products 3. In a 20 mL
reaction tube was charged with enaminone 1 (0.2 mmol, 1 equiv),
HPO(OR) 2 (0.4 mmol, 2 equiv), Cu(OTf) (0.04 mmol, 20 mol
PET EA
1
3
2
2
%
), p-TSA (0.4 mmol, 2 equiv), and CH CN (2 mL). The tube was
then sealed with a Teflon cap, and the mixture was stirred at 80 or 100
C for 12 h with oil bath heating. Until completion of the reaction
TLC), the resultant mixture was allowed to cool down to an ambient
temperature and was diluted with ethyl acetate. The liquid was then
transferred into a round-bottom flask for subsequent rotary
evaporation. After removing the solvent at reduced temperature, the
resulting residue was subjected to flash silica gel column
chromatography to provide pure products with the elution of mixed
petroleum ether/ethyl acetate (v/v = 3:1 or 2:1).
3
1
3
1
= 22.0
= 5.0 Hz), 132.7,
= 22.0 Hz),
C−F
= 6.0 Hz); P NMR (162 MHz,
3
C−P
1
4
°
(
= 255.0 Hz), 139.8 (d, J
C−F
C−F
2
3
1
C−P
1
9
3
3
+
1
3
16
4
Diethyl (E)-(3-(4-Chlorophenyl)-3-oxoprop-1-en-1-yl)-
PET EA
1
5
1
Diethyl (E)-(3-Oxo-3-phenylprop-1-en-1-yl)phosphonate (3a):
eluent, vPET/vEA = 3:1; colorless oil (40 mg, 75% yield); H NMR
3
1
1
3
1
(
2
6
400 MHz, CDCl ) δ 8.01 (d, J = 7.4 Hz, 2H), 7.90−7.76 (dd, J =
3
0.8, 16.8 Hz,1 H), 7.63 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H),
.96 (t, J = 17.8 Hz, 1H), 4.18 (m, J = 6.8 Hz, 4H), 1.38 (t, J = 7.0
3
C−P
= 4.0 Hz), 132.4, 130.6, 130.3, 129.3, 62.6, 16.4 (d, JC−P = 5.0
C−P
13
1
31
Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 188.5 (d, J
= 22.0
3
C−P
3
+
Hz), 140.2 (d, JC−P = 6.0 Hz), 136.3, 133.9, 131.8, 130.0, 128.9 (d,
JC−P = 4.0 Hz), 62.5 (d, JC−P = 5.0 Hz), 16.4 (d, JC−P = 5.0 Hz);
13
16
4
3
1
P
Diethyl (E)-(3-(3-Chlorophenyl)-3-oxoprop-1-en-1-yl)-
NMR (162 MHz, CDCl ) δ 16.0.
3
PET EA
1
Diethyl (E)-(3-Oxo-3-(p-tolyl)prop-1-en-1-yl)phosphonate (3b):
eluent, vPET/vEA = 3:1; colorless oil (42 mg, 74% yield); H NMR
3
1
(
1
1
400 MHz, CDCl ) δ 7.92 (d, J = 8.0 Hz, 2H), 7.83 (dd, J = 20.8,
3
1
3
1
6.8 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 6.93 (dd, J = 19.6, 16.8 Hz,
H), 4.15 (p, 4H), 2.44 (s, 3H), 1.37 (t, J = 7.0 Hz, 6 H); C{ H}
1
3
1
3
C−P
NMR (100 MHz, CDCl ) δ 188.0 (d, J
= 22.0 Hz), 145.0, 140.4
= 6.0
3
C−P
C−P
3
1
(
6
d, JC−P = 6.0 Hz), 133.8, 131.2, 129.6, 129.4, 129.1, 62.5 (d, J
.0 Hz), 21.8, 16.4 (d, JC−P = 6.0 Hz); P NMR (162 MHz, CDCl )
=
3
C−P
3
3
1
+
13 16
4
+
δ 16.2; ESI-HRMS calcd for C H O PNa [M + Na] 305.0913,
1
4
19
4
found 305.0913.
Diethyl (E)-(3-(4-Bromophenyl)-3-oxoprop-1-en-1-yl)-
Diethyl (E)-(3-Oxo-3-(m-tolyl)prop-1-en-1-yl)phosphonate (3c):
eluent, vPET/vEA = 3:1; colorless oil (42 mg, 74% yield); H NMR
PET EA
1
1
3
(
(
400 MHz, CDCl ) δ 7.89−7.77 (m, 3H), 7.45−7.28 (m, 2H), 6.94
7.78 (dd, J = 20.8, 16.8 Hz, 1H), 7.66 (d, J = 8.6 Hz, 2H), 6.96 (dd, J
= 18.8, 16.8 Hz, 1H), 4.17 (p, J = 7.8, 7.4 Hz, 4H), 1.37 (t, J = 7.0 Hz,
3
dd, J = 19.2, 16.8 Hz, 1H), 4.21−4.13 (m, 4H), 2.44 (s, 3H), 1.37 (t,
13
1
13
1
J = 7.2 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 188.7 (d, J
6 H); C{ H} NMR (100 MHz, CDCl ) δ 187.5 (d, J
= 22.0 Hz),
3
C−P
3
C−P
22.0 Hz), 140.4 (d, JC−P = 6 Hz), 138.8, 136.3, 134.7, 131.5, 129.6,
139.5 (d, JC−P = 10.0 Hz), 135.0, 132.4, 132.3, 130.6, 130.4, 129.3,
3
1
C−P
62.6 (d, JC−P = 5.0 Hz), 16.4 (d, JC−P = 6.0 Hz); P NMR (162 MHz,
31
+
3
CDCl ) δ 15.6; ESI-HRMS calcd for C H BrO PNa [M + Na]
3
13 16
4
+
14
19
4
368.9862, found 368.9865.
Diethyl (E)-(3-Oxo-3-(o-tolyl)prop-1-en-1-yl)phosphonate (3d):
Diethyl (E)-(3-(4-Iodophenyl)-3-oxoprop-1-en-1-yl)phosphonate
1
1
(3k): eluent, vPET/v = 3:1; colorless oil (46 mg, 58% yield); H
EA
NMR (400 MHz, CDCl ) δ 7.89 (d, J = 8.4 Hz, 2H), 7.75 (p, 3H),
3
3
6.96 (dd, J = 19.2, 17.2 Hz, 1H), 4.18 (p, J = 7.8, 7.4 Hz, 4H), 1.37 (t,
1
13
1
J = 7.2 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 187.8 (d, J
3 C−P
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Note
=
22.0 Hz), 139.5 (d, JC−P = 6.0 Hz), 138.2, 135.5 (d, JC−P = 2.0 Hz),
JC−P = 22.0 Hz), 140.4 (d, JC−P = 6.0 Hz), 135.9, 133.7, 132.5, 131.5,
131.2, 129.8, 129.7, 129.1, 128.9, 127.8, 127.1, 124.1, 62.6 (d, J
1
32.3, 130.5, 130.2, 102.3, 62.6 (d, J = 5.0 Hz), 16.4 (d, JC−P = 6.0
=
C−P
C−P
3
1
31
Hz); P NMR (162 MHz, CDCl ) δ 15.6; ESI-HRMS calcd for
6.0 Hz), 16.4 (d, JC−P = 7.0 Hz); P NMR (162 MHz, CDCl ) δ
3
3
+
+
C H IO Na [M + Na] 416.9723, found 416.9728.
16.1; ESI-HRMS calcd for C H O PNa [M + Na] 341.0913, found
13
16
4
17 19
4
Diethyl (E)-(3-Oxo-3-(4-(trifluoromethyl)phenyl)prop-1-en-1-yl)-
341.0919.
phosphonate (3l): eluent, v /v = 2.5:1; colorless oil (37 mg, 55%
Diethyl (E)-(3-Oxo-3-(thiophen-2-yl)prop-1-en-1-yl)phosphonate
(3s): eluent, vPET/v = 3:1; colorless oil (36 mg, 66% yield); H
PET EA
1
1
yield); H NMR (400 MHz, CDCl ) δ 8.11 (d, J = 8.2 Hz, 2H), 7.78
3
EA
(
1
1
(
1
d, J = 8.0 Hz, 3H), 7.01 (t, J = 17.0 Hz, 1H), 4.19 (t, J = 6.9 Hz, 4H),
NMR (400 MHz, CDCl ) δ 7.89 (d, J = 3.4 Hz, 1H), 7.77 (d, J = 4.8
3
1
3
1
.38 (t, J = 6.9 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 187.8,
Hz, 1H), 7.68 (t, J = 19.2 Hz, 1H), 7.21 (t, 1H), 7.01 (t, J = 17.4 Hz,
3
1
3
1
39.3 (d, JC−P = 5.0 Hz), 138.9, 135.2 (q, J
= 201.0 Hz), 125.9
1H), 4.21−4.13 (m, 4H), 1.37 (t, J = 7.0 Hz, 6 H); C{ H} NMR
C−F
3
1
d,J
= 4.0 Hz), 122.1, 62.6, 16.4; P NMR (162 MHz, CDCl ) δ
(100 MHz, CDCl ) δ 180.2, 144.0, 139.9, 135.9, 133.7, 131.4, 128.7,
C−P
3
3
1
9
31
7.1; F NMR (376 MHz, CDCl ) δ −63.3 (s, 3 F); ESI-HRMS
62.6, 16.4; P NMR (162 MHz, CDCl ) δ 16.2; ESI-HRMS calcd for
3
3
+
+
calcd for C H F O PNa [M + Na] 359.0630, found 359.0630.
C H O PSNa [M + Na] 297.0321, found 297.0326.
14
16
3
4
11 15
4
Diethyl (E)-(3-(4-Isocyanophenyl)-3-oxoprop-1-en-1-yl)-
Diethyl (E)-(3-(Furan-2-yl)-3-oxoprop-1-en-1-yl)phosphonate
1
phosphonate (3m): eluent, v /v = 3:1; colorless oil (26 mg,
4
7
4
1
1
1
(3t): eluent, vPET/v = 2:1; colorless oil (28 mg, 54% yield); H
PET EA
EA
1
4% yield); H NMR (400 MHz, CDCl ) δ 8.12 (d, J = 8.2 Hz, 2H),
NMR (400 MHz, CDCl ) δ 7.74−7.64 (m, 2H), 7.42 (d, J = 3.6 Hz,
3
3
.83 (t, J = 8.2 Hz, 3H), 7.00 (t, J = 17.4 Hz, 1H), 4.23−4.14 (m,
1H), 7.03 (dd, J = 19.2, 17.2 Hz, 1H), 6.63 (dd, J = 3.6, 1.6 Hz, 1H),
1
3
1
13
1
H), 1.38 (t, J = 7.0 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ
4.16 (q, 4H), 1.37 (t, J = 7.2 Hz, 6 H); C{ H} NMR (100 MHz,
CDCl ) δ 175.6, 152.5, 147.9, 139.5 (d, J = 7.0 Hz), 131.2, 129.3,
3
87.4, 139.2 (d, JC−P = 8.0 Hz), 133.3, 132.7, 131.4, 129.3, 117.7,
3
C−P
3
1
31
17.1, 62.9, 16.4 (d, JC−P = 5.0 Hz); P NMR (162 MHz, CDCl ) δ
119.9, 112.9, 62.6 (d, JC−P = 5.0 Hz), 16.4 (d, JC−P = 6.0 Hz);
P
3
+
5.4; ESI-HRMS calcd for C H NO PNa [M + Na] 316.0709,
NMR (162 MHz, CDCl ) δ 15.8; ESI-HRMS calcd for C H O PNa
1
4
16
4
3
11 15
5
+
found 316.0708.
[M + Na] 281.0549, found 281.0549.
Diethyl (E)-(3-(4-(Dimethylamino)phenyl)-3-oxoprop-1-en-1-yl)-
Dimethyl (E)-(3-Oxo-3-phenylprop-1-en-1-yl)phosphonate (3u):
eluent, vPET/vEA = 3:1; colorless oil (38 mg, 79% yield); H NMR
1
phosphonate (3n): eluent, v /v = 2:1; colorless oil (27 mg, 43%
PET EA
1
yield); H NMR (400 MHz, CDCl ) δ 7.97 (d, J = 8.8 Hz, 2H), 7.87
(400 MHz, CDCl ) δ 8.01 (d, J = 7.8 Hz, 2H), 7.85 (dd, J = 20.8,
3
3
(
q, 1H), 6.90 (dd, J = 20.4, 16.8 Hz, 1H), 6.69 (d, J = 8.8 Hz, 2H),
17.2 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.52 (t, J = 7.4 Hz, 2H), 6.92
1
3
1
4
.14 (q, J = 7.2 Hz, 4H), 3.10 (s, 6 H), 1.36 (t, J = 7.0 Hz, 6 H);
(t, J = 18.2 Hz, 1H), 3.82 (d, J = 11.0 Hz, 6 H); C{ H} NMR (100
MHz, CDCl ) δ 188.4 (d, J = 22.0 Hz), 141.0 (d, JC−P = 6.0 Hz),
13
1
C{ H} NMR (100 MHz, CDCl ) δ 185.4 (d, J
= 22.0 Hz),
3
C−P
3
C−P
1
53.9, 141.2 (d, JC−P = 6.0 Hz), 131.5, 129.1, 127.3, 124.4, 111.0, 62.3
136.2, 133.9, 130.3, 128.9 (d, J
= 3.0 Hz), 128.4, 52.9 (d, JC−P =
3
C−P
3
1
31
(
d, JC−P = 5.0 Hz), 40.1, 16.4 (d, JC−P = 7.0 Hz); P NMR (162
6.0 Hz); P NMR (162 MHz, CDCl ) δ 18.8; ESI-HRMS calcd for
+
MHz, CDCl ) δ 17.2; ESI-HRMS calcd for C H NO PNa[M +
C H O PNa [M + Na] 263.0444, found 263.0443.
3
15 22
4
11 13
4
+
Na] 334.1179, found 334.1180.
Dethyl (E)-(3-(4-Methoxyphenyl)-3-oxoprop-1-en-1-yl)-
Diethyl (E)-(3-(3,4-Dichlorophenyl)-3-oxoprop-1-en-1-yl)-
phosphonate (3v): eluent, vPET/vEA = 3:1; colorless oil (39 mg,
1
phosphonate (3o): eluent, v /v = 3:1; colorless oil (40 mg,
77% yield); H NMR (400 MHz, CDCl ) δ 7.91 (t, 2H), 7.84 (t,
PET EA
3
1
6
7
1
0% yield); H NMR (400 MHz, CDCl ) δ 8.02 (d, J = 1.4 Hz, 1H),
1H), 7.31 (d, J = 8.0 Hz, 2H), 6.90 (dd, J = 19.6, 17.2 Hz, 1H), 3.81
3
1
3
1
.78 (t, 1H), 7.67 (dd, J = 20.8, 16.8 Hz, 1H), 7.53 (d, J = 8.4 Hz,
H), 6.91 (dd, J = 18.4, 16.8 Hz, 1H), 4.10 (p, J = 6.6 Hz, 4H), 1.30
(d, J = 11.2 Hz, 6 H), 2.44 (s, 3 H); C{ H} NMR (100 MHz,
CDCl ) δ 187.8 (d, J = 22.0 Hz), 145.1, 141.3 (d, JC−P = 6.0 Hz),
3
C−P
1
3
1
(t, J = 7.0 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 185.3 (d,
133.7, 129.7 (d, J
= 6.0 Hz), 129.1, 127.8, 52.8 (d, JC−P = 8.0 Hz),
3
C−P
3
1
JC−P = 22 Hz),137.9 (d, JC−P = 6.0 Hz), 134.8, 132.8, 132.1, 130.3,
21.7; P NMR (162 MHz, CDCl ) δ 19.0; ESI-HRMS calcd for
3
+
1
30.0, 129.8, 126.8, 61.6 (d, JC−P = 5.0 Hz), 15.4 (d, JC−P = 6.0 Hz);
C H O PNa [M + Na] 277.0600, found 277.0606.
12
15
4
3
1
P NMR (162 MHz, CDCl ) δ 15.2; ESI-HRMS calcd for
Dmethyl (E)-(3-(4-Chlorophenyl)-3-oxoprop-1-en-1-yl)-
3
+
phosphonate (3w): eluent, v /v = 3:1; colorless oil (38 mg,
C H Cl O PNa [M + Na] 358.9977, found 358.9979.
PET EA
13
15
2
4
1
6
9% yield); H NMR (400 MHz, CDCl ) δ 7.96 (d, J = 8.2 Hz, 2H),
Diethyl (E)-(3-(Benzo[d][1,3]dioxol-5-yl)-3-oxoprop-1-en-1-yl)-
3
phosphonate (3p): eluent, v /v = 2:1; colorless oil (43 mg,
6
7.79 (t, J = 17.8 Hz, 1H), 7.49 (d, J = 8.2 Hz, 2H), 6.97 (t, J = 16.4
Hz, 1H), 3.82 (d, J = 7.4 Hz, 6 H); C{ H} NMR (100 MHz,
PET EA
1
13
1
9% yield); H NMR (400 MHz, CDCl ) δ 7.78 (dd, J = 20.8, 16.8
3
3
1
Hz, 1H), 7.64 (dd, J = 8.0, 1.6 Hz, 1H), 7.49 (d, J = 1.6 Hz, 1H),
.96−6.87 (m, 2H), 6.08 (s, 2H), 4.16 (p, J = 8.6, 7.8 Hz, 4H), 1.37
CDCl
3
) δ 187.1, 140.6, 140.4, 134.5, 131.3, 130.4, 129.3, 52.9;
P
6
NMR (162 MHz, CDCl
3
) δ 20.7; ESI-HRMS calcd for
PNa [M + Na] 297.0054, found 297.0056.
1
3
1
+
(t, J = 7.0 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 186.3 (d,
C
H
11
12ClO
4
3
JC−P = 22.0 Hz), 152.7, 148.6, 140.2 (d, JC−P = 6.0 Hz), 131.2 (d, JC−P
15.0 Hz), 129.2, 125.8, 108.4 (d, J = 20.0 Hz), 102.1, 62.5 (d,
Diisopropyl (E)-(3-Oxo-3-phenylprop-1-en-1-yl)phosphonate
1
(
3x): eluent, vPET/v = 2:1; colorless oil (37 mg, 63% yield); H
=
EA
C−P
3
1
NMR (400 MHz, CDCl ) δ 8.01 (d, J = 8.6 Hz, 2H), 7.81 (dd, J =
JC−P = 6.0 Hz), 16.4 (d, JC−P = 6 Hz); P NMR (162 MHz, CDCl ) δ
3
3
+
21.0, 17.0 Hz, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H),
1
6.2; ESI-HRMS calcd for C H O PNa [M + Na] 335.0655, found
14 17 6
6
.95 (dd, J = 19.0, 16.8 Hz, 1H), 4.79−4.72 (m, 2H), 1.39 (d, J = 6.2
3
35.0656.
Diethyl (E)-(3-(Naphthalen-2-yl)-3-oxoprop-1-en-1-yl)-
phosphonate (3q): eluent, v /v = 3:1; colorless oil (29 mg,
13 1
Hz, 6 H), 1.35 (d, J = 6.2 Hz, 6 H); C{ H} NMR (100 MHz,
CDCl ) δ 188.7 (d, JC−P = 22.0 Hz), 139.3 (d, JC−P = 6.0 Hz), 136.4,
133.8, 133.3, 131.4, 128.9 (d, JC−P = 3.0 Hz), 71.4 (d, JC−P = 6.0 Hz),
PET EA
3
1
4
8
6
7
2
1
6% yield); H NMR (400 MHz, CDCl ) δ 8.55 (d, J = 8.6 Hz, 1H),
3
3
1
.05 (d, J = 8.2 Hz, 1H), 7.90 (t, J = 6.6 Hz, 2H), 7.71−7.52 (m, 4H),
24.1 (dd, JC−P = 3.0 Hz, 7.0 Hz); P NMR (162 MHz, CDCl
13.5; ESI-HRMS calcd for C15
297.1251.
Dibutyl (E)-(3-Oxo-3-phenylprop-1-en-1-yl)phosphonate (3y):
eluent, vPET/vEA = 3:1; colorless oil (41 mg, 63% yield); H NMR
3
) δ
H O P [M + H] 297.1250, found
22 4
+
.88 (dd, J = 18.8, 17.2 Hz, 1H), 4.19 (q, J = 7.4 Hz, 4H), 1.37 (t, J =
.0 Hz, 6 H); 13C{ H} NMR (100 MHz, CDCl ) δ 192.2 (d, J
1
=
3
C−P
2 Hz), 143.6 (d, JC−P = 5.0 Hz), 134.3, 133.9, 133.6, 132.0, 130.5,
30.2, 129.3, 128.6, 128.3, 126.8, 125.6, 124.4, 62.6 (d, J = 5.0
1
C−P
3
1
Hz), 16.5 (d, JC−P = 5.0 Hz); P NMR (162 MHz, CDCl ) δ 15.8;
(400 MHz, CDCl ) δ 8.02 (d, J = 7.4 Hz, 2H), 7.84 (dd, J = 21.0,
3
3
+
ESI-HRMS calcd for C H O PNa [M + Na] 341.0913, found
16.8 Hz, 1H), 7.67−7.62 (m, 1H), 7.52 (t, J = 7.6 Hz, 2H), 6.95 (dd,
J = 19.2, 17.0 Hz, 1H), 4.11−4.07 (m, 4H), 1.70−1.67 (m, 4H),
1
7
19
4
3
41.0913.
Diethyl (E)-(3-(Naphthalen-2-yl)-3-oxoprop-1-en-1-yl)-
phosphonate (3r): eluent, v /v = 3:1; colorless oil (32 mg,
1
3
1.45−1.41 (m, 4H), 0.95 (t, 6 H); C NMR (100 MHz, CDCl
) δ
3
188.6 (d, J
= 22.0 Hz), 140.1 (d, J
= 6.0 Hz), 136.3, 133.9,
PET EA
C−P
C−P
1
5
0% yield); H NMR (400 MHz, CDCl ) δ 8.56 (s, 1H), 8.09−7.98
131.7, 129.9, 128.9 (d, JC−P = 4.0 Hz), 66.2 (d, J
JC−P = 7 Hz), 18.7, 13.6 (d, JC−P = 4 Hz); P NMR (162 MHz,
= 6 Hz), 32.5 (d,
C−P
3
3
1
(m, 3H), 7.91 (dd, J = 17.0, 8.4 Hz, 2H), 7.61 (dt, J = 21.8, 7.2 Hz,
+
2
H), 7.02 (dd, J = 19.4, 17.0 Hz, 1H), 4.21 (q, J = 7.2 Hz, 4H), 1.39
CDCl ) δ 15.9; ESI-HRMS calcd for C H O P [M + H] 325.1563,
3
17 26
4
1
3
1
(t, J = 7.0 Hz, 6 H); C{ H} NMR (100 MHz, CDCl ) δ 188.1 (d,
found 325.1567.
3
9
865
https://doi.org/10.1021/acs.joc.1c00862
J. Org. Chem. 2021, 86, 9861−9868

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1
Dibenzyl (E)-(3-Oxo-3-phenylprop-1-en-1-yl)phosphonate (3z):
eluent, vPET/vEA = 3:1; colorless oil (44 mg, 56% yield); H NMR
mg, 50% yield); H NMR (400 MHz, CDCl ): δ 7.92 (d, J = 8.0 Hz,
3
1
2H), 7.75 (s, 1H), 7.65 (t, J = 7.4 Hz, 1H), 7.57 (d, J = 7.8 Hz, 2H),
7.54−7.50 (m, 3H), 7.06 (t, 2H), 5.57 (t, J = 17.2 Hz, 1H), 4.06 (t,
4H), 1.73 (s, 1H), 1.30 (t, J = 7.0 Hz, 6 H); C{ H} NMR (100
MHz, CDCl ) δ 186.0, 146.0, 145.9, 138.1, 133.5, 130.6, 130.1, 129.2,
128.5, 127.9, 127.8, 62.2, 16.4; P NMR (162 MHz, CDCl
ESI-HRMS calcd for C19
445.0958.
(
1
1
400 MHz, CDCl ) δ 7.88 (d, J = 7.6 Hz, 2H), 7.70 (t, 1H), 7.60 (t,
3
1
3
1
H), 7.47 (t, J = 7.6 Hz, 2H), 7.37−7.34 (m, 10 H), 6.89 (dd, J =
1
3
1
9.8, 17.0 Hz, 1H), 5.11−5.06 (m, 4 H); C{ H} NMR (100 MHz,
3
3
1
CDCl ) δ 188.4 (d, J
= 23.0 Hz), 140.2 (d, J = 7.0 Hz), 136.2,
3
) δ 17.0;
H N O PSNa [M + Na] 445.0958, found
23 2 5
3
C−P
C−P
+
1
1
1
35.7 (d, JC−P = 6.0 Hz), 135.6 (d, JC−P = 6.0 Hz), 133.9, 131.3,
29.5, 128.9 (d, JC−P = 7.0 Hz), 128.7 (d, JC−P = 2.0 Hz), 128.5,
3
1
28.2, 128.1, 68.1 (d, JC−P = 5.0 Hz), 67.4 (d, JC−P = 6.0 Hz);
P
NMR (162 MHz, CDCl ) δ 17.0; ESI-HRMS calcd for C H O P
ASSOCIATED CONTENT
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00862.
3
23 22
4
■
+
[
M + H] 393.1250, found 393.1260.
Experimental Procedure for the Synthesis of Compound 4.
*
In a 15 mL test tube was charged with alkenylphosphate 3a (0.1
mmol, 1 equiv), morpholine (0.2 mmol, 2 equiv), and dry CH CN (2
3
mL). The mixture was then stirred at room temperature for 4 h with
oil bath heating. Upon completion (TLC), the reaction mixture was
diluted with ethyl acetate and transferred to a round-bottom flask.
The liquid was then transferred into a round-bottom flask for
subsequent rotary evaporation. After removing the solvent at reduced
pressure, the resulting residue was purified by silica gel column
chromatography by using mixed petroleum ether and ethyl acetate (v/
v = 1:1) as an eluent to provide the pure product.
Experimental procedures, characterization data, and
NMR spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
Yunyun Liu − College of Chemistry and Chemical Engineering,
Jiangxi Normal University, Nanchang 330022, People’s
Republic of China; orcid.org/0000-0002-5553-1672;
Email: chemliuyunyun@jxnu.edu.cn
Jie-Ping Wan − College of Chemistry and Chemical
Engineering, Jiangxi Normal University, Nanchang 330022,
People’s Republic of China; orcid.org/0000-0002-9367-
8384; Email: wanjieping@jxnu.edu.cn
Diethyl (2-Morpholino-3-oxo-3-phenylpropyl)phosphonate (4):
1
eluent, vPET/vEA = 2:1; colorless oil (29 mg, 82% yield); H NMR
(
400 MHz, CDCl ) δ: 7.98 (d, J = 7.4 Hz, 2H), 7.59 (t, J = 7.4 Hz,
3
1
2
3
H), 7.49 (t, J = 7.6 Hz, 2H), 4.25- 4.18 (m, 2H), 4.11−4.04 (m,
H), 3.86−3.78 (m, 1H), 3.62−3.55 (m, 4H), 3.46−3.38 (m, 1H),
.28−3.20 (m, 1H), 2.87−2.81 (m, 2H), 2.79−2.73 (m, 2H), 1.36 (t,
1
3
1
J = 7.0 Hz, 3H), 1.25 (t, J = 7.2 Hz, 3 H); C{ H} NMR (100 MHz,
CDCl ) δ 197.7 (d, J
= 12.0 Hz), 136.8, 133.4, 128.7, 128.1, 67.5,
3
C−P
Authors
6
2.9 (d, JC−P = 12.0 Hz), 61.5 (d, JC−P = 7.0 Hz), 58.7, 57.2, 50.8 (d,
JC−P = 6.0 Hz), 34.5 (d, JC−P = 8.0 Hz), 16.6 (d, JC−P = 26.0 Hz);
3
1
Ting Liu − College of Chemistry and Chemical Engineering,
Jiangxi Normal University, Nanchang 330022, People’s
Republic of China
Li Wei − College of Chemistry and Chemical Engineering,
Jiangxi Normal University, Nanchang 330022, People’s
Republic of China
Baoli Zhao − College of Chemistry and Chemical Engineering,
Jiangxi Normal University, Nanchang 330022, People’s
Republic of China; Zhejiang Key Laboratory of Alternative
Technologies for Fine Chemicals Process, Shaoxing University,
Shaoxing 312000, People’s Republic of China
P
NMR (162 MHz, CDCl ) δ 25.4; ESI-HRMS calcd for
3
+
C H NO PNa [M + Na] 378.1441, found 378.1441.
17
26
5
Experimental Procedure for the Synthesis of Compound 5.
In a 15 mL reaction tube was equipped with alkenylphosphate 3a (0.1
mmol, 1 equiv), octanethiol (0.1 mmol, 1 equiv), K CO (0.1 mmol,
2
3
1
equiv), and CH Cl (2 mL). The mixture was then stirred at room
2 2
temperature for 4 h. Upon completion (TLC), the reaction mixture
diluted with ethyl acetate and transferred into a round-bottom flask.
After removing the solvent at reduced temperature, the resulting
mixture was purified by silica gel column chromatography with the
election of mixed petroleum ether and ethyl acetate (v/v = 1:1).
Diethyl (2-(Octylthio)-3-oxo-3-phenylpropyl)phosphonate (5):
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00862
1
eluent, vPET/vEA = 1:1; colorless oil (30 mg, 72% yield); H NMR
(
(
2
1
(
400 MHz, CDCl ) δ 8.00−7.96 (m, 2H), 7.61−7.56 (m, 1H), 7.48
3
t, J = 7.6 Hz, 2H), 4.25−4.17 (m, 4H), 3.61−3.34 (m, 3H), 2.88−
Notes
.73 (m, 2H), 1.63−1.55 (m, 2H), 1.34 (td, J = 7.2, 1.4 Hz, 8 H),
13 1
The authors declare no competing financial interest.
.27 (d, J = 16.0 Hz, 8 H), 0.87 (t, J = 7.0 Hz, 3 H); C{ H} NMR
= 13.0 Hz), 136.6 (d, JC−P = 1.0
100 MHz, CDCl ) δ 196.2 (d, J
3
C−P
ACKNOWLEDGMENTS
Hz), 133.4, 128.7 (d, JC−P = 2.0 Hz), 128.2, 77.3, 63.2 (dd, JC−P
=
■
1
2
1
0.0 Hz), 39.7 (d, JC−P = 1.0 Hz), 35.2, 33.7 (d, JC−P = 5.0 Hz), 31.8,
The work is financially supported by the National Natural
Science Foundation of China (21861019) and the Natural
Science Foundation of Jiangxi Province (20202ACBL203006).
9.2 (d, J
= 3.0 Hz), 28.8, 22.6, 16.5 (dd, JC−P = 6.0 Hz, 4 Hz),
C−P
4.1; 31P NMR (162 MHz, CDCl ) δ 26.1; ESI-HRMS calcd for
3
+
C H O PSNa [M + Na] 437.1886, found 437.1886.
21
35
4
Experimental Procedure for the Synthesis of Sulfonyl
REFERENCES
Hydrazine 6. In a 10 mL reaction tube was charged with
alkenylphosphate 3a (0.1 mmol, 1 equiv), benzenesulfonyl hydrazine
(
■
(1) (a) Sawa, M.; Kiyoi, T.; Kurokawa, K.; Kumihara, H.;
Yamamoto, M.; Miyasaka, T.; Ito, Y.; Hirayama, R.; Inoue, T.; Kirii,
Y.; Nishiwaki, E.; Ohmoto, H.; Maeda, Y.; Ishibushi, E.; Inoue, Y.;
Yoshino, K.; Kondo, H. New type of metalloproteinase inhibitor:
design and synthesis of new phosphonamide-based hydroxamic acids.
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D.; Wang, Y.; Grzegorzewicz, A. E.; Scherman, M. S.; Napper, A. D.;
McCammon, J. A.; Lee, R. E.; Diamond, S. L.; McNeil, M.
Identification of triazinoindol-benzimidazolones as nanomolar inhib-
itors of the Mycobacterium tuberculosis enzyme TDP-6-deoxy-d-xylo-
4-hexopyranosid-4-ulose 3,5-epimerase (RmlC). Bioorg. Med. Chem.
2010, 18, 896−908. (c) Kumar, T. S.; Zhou, S.; Joshi, B. V.;
Balasubramanian, R.; Yang, T.; Liang, B. T.; Jacobson, K. A. Structure-
0.15 mmol, 1.5 equiv), and DMSO (2 mL). The mixture was then
stirred at 70 °C for 5 h with oil bath heating. Upon completion
TLC), 5 mL water and 5 mL ethyl acetate were added to the tube.
(
The heterogeneous mixture was extracted with ethyl acetate (3 × 10
mL). The combined organic phase was dried over anhydrous Na SO .
2
4
After filtration, the acquired solution was collected, and the solvent
was removed at reduced pressure. The residue obtained therein was
subjected to flash silica gel column chromatography to provide pure
products with the elution of mixed petroleum ether/ethyl acetate (v/v
=
2:1)
Diethyl (1E,3Z)-3-Phenyl-3-(2-(phenylsulfonyl)hydrazono)prop-
1
-en-1-yl)phosphonate (6): eluent, v /v = 2:1; colorless oil (21
PET EA
9
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