Lewis Acid Enables Ketone Phosphorylation: Synthesis of Alkenyl Phosphonates

Article abstract of DOI:10.1002/cjoc.202100083

An efficient Lewis acid enabled ketones phosphonylation to synthesize vinylphosphonates has been developed. This method relays on ketone hydrophosphonylation/α-hydroxy phosphonates unimolecular elimination (E1) dehydration cascade reaction sequence. Vario

Full text of DOI:10.1002/cjoc.202100083

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Title: Lewis Acid Enables Ketone Phosphorylation: Synthesis of Alkenyl
Phosphonates
Authors: Xiao-Hong Wei,* Chun-Yuan Bai, Lian-Biao Zhao, Ping Zhang, Zhen-Hua Li,
Yan-Bin Wang and Qiong Su*
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Cite this paper:Chin. J. Chem.2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
Lewis Acid Enables Ketone Phosphorylation: Synthesis of Alkenyl
Phosphonates
Xiao-Hong Wei,*,a Chun-Yuan Bai, a Lian-Biao Zhao, a Ping Zhang, a Zhen-Hua Li, a Yan-Bin Wang a and Qiong Su*,a
aKey Laboratory for Utility of Environment-Friendly Composite Materials and Biomass in University of Gansu Province, College of Chemical
Engineering, Northwest Minzu University, No. 1, Northwest Xincun, Lanzhou, 730030, P.R. China.
Keywords
Ketone | Phosphorylation | Alkenyl Phosphonates | Lewis Acid | Cascade Reaction
Main observation and conclusion
An efficient Lewis acid enabled ketones phosphonylation to synthesis vinylphosphonates has been developed. This method relays on
ketone hydrophosphonylation/α-hydroxy phosphonates unimolecular elimination (E1) dehydration cascade reaction sequence. Vari-
ous of C-P bond formation product were obtained in moderate to excellent yields with the water as the only byproduct in the reaction.
Comprehensive Graphic Content
*E-mail: weixh12@lzu.edu.cn; hgsq@xbmu.edu.cn
View HTML Article
Supporting Information
Chin. J. Chem. 2021,39, XXX－XXX
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through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1002/cjoc.202100083
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First authoret al.
Report
Background and Originality Content
Results and Discussion
Organophosphonate compounds and their derivatives
play important role in medicinal and material chemistry due
to their unique biological and chemical activities.[1] In partic-
ular, dialkyl phosphonates exhibit a broad spectrum of signif-
icant biological activities (Figure 1).[2] In addition, phospho-
nates have also wide application in synthetic chemistry, for
example, as key reagent in the stereoselective olefination
process via Horner-Wadsworth-Emmons reactions, or serve
as chiral auxiliaries to provide enantioselective control in the
reaction.[3] Among them, vinylphosphonate compounds have
shown exceptional application: they can be easily converted
into chiral phosphonates by well developed asymmetric hy-
drogenation;[4] they are crucial building blocks and important
synthetic intermediates in the construction of functional-
phosphorus compounds,[5] such as aminophosphonic
acids[5a-d] and poly(vinylphosphonates);[5e] As a result, the
development of efficient methods toward vinylphosphonates
compounds have gained significant attention.[6]
Table 1 Optimization of the reaction conditions
Entry
1
Catalyst
AgOTf
Additive
Solvent
DCE
DCE
DCE
CH3CN
CH3Ph
THF
Yield(%)a, b
50%
trace
trace
NR
2
AgTFA
AgNO3
AgOTf
3
4
5
AgOTf
32%
trace
40%
41%
15%
32%
70%
84%
60%
73%
50%
52%
53%
51%
64%
80%
37%
6
AgOTf
7
AgOTf
HOAc
PivOH
TsOH
CF3COOH
Tf2O
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
8
AgOTf
9
AgOTf
10
11
12
13c
14d
15
16
17
18
19
20e
21
AgOTf
AgOTf
AgOTf
AgOTf
HOTf
HOTf
HOTf
HOTf
HOTf
HOTf
HOTf
HOTf
HOTf
HOTf
H
O
O
H
O
P
O
O
H
O
AgOTf
l
C
P
Et
O
)( )
O
H
(
P
N
O
H
C
3
H
O
O
Ni(OTf)2
Al(OTf)3
Fe(OTf)2
Mg(OTf)2
Ti(OiPr)4
AgOTf
O
e
M
O
H
n
or
I hibit
osm om c n ana o ue
id y i
osm om c n
F id y i
F
l
g
Figure 1 Phosphonate antibiotics.
The most widely used approach in the area is met-
al-catalyzed coupling of P(O)H compounds with activated
vinyl substrates, including vinyl boronophosphonates,[7] hal-
ogen,[8] sulfonate,[9] phosphite ester[6i] or α-stannylated vi-
nylphosphonates,[10] and others[11] (Scheme 1). However,
these materials were neither easily available nor environ-
mentally friendly. Recently, Han’s group developed a highly
efficient route to synthesize vinylphosphonate compounds
via palladium-catalyzed addition reaction of P(O)H com-
pounds to alkynes reaction (Scheme 1).[6d, 12] However, only
moderate efficiency was achieved in regio- and ste-
reo-selectivity control from their study. Feng’s
group[13]developed a highly efficient synthesis of α-hydroxy
a Reaction conditions: 1a (0.1 mmol), dimethyl phosphonate (2.5 equiv),
o
b
catalyst (0.1 equiv), additive (1 equiv), solvent (1 mL) , 110 C, air, 15 h.
c
d
Isolated yield by column chromatography. HOTf (0.5 equiv). HOTf (1.5
equiv). e argon conditions
In the initial study, we used the 1-(4-methoxyphenyl)ethanone
1a and dimethyl phosphonate 2a as the model substrates and
firstly tested different silver salts as the Lewis acid catalyst in reac-
tion (Table 1, entries 1-3, see supporting information for details).
To our delight, the desired vinylphosphonate product 3aa was
obtained in 50% yield by using AgOTf as catalyst (Table 1, entry 1).
Meanwhile, different solvents screening indicated that DCE was
the best choice (Table 1, entries 4-6). Next, we believed that the
acid additives should play a key role in the reaction, so we further
screening acid additives. It was found that HOTf was the best
choice, affording the desired product 3aa in 84% yield (Table 1,
entries 7-12). When the reaction temperature was increased to
120 oC or decreased to 100 oC, the yield of 3aa decreased to some
extent (Table 1, entries 13-14). We also applied other Lewis acid in
the reaction, Although all of them can catalyzed the reaction,
AgOTf was still the better catalyst under the condition (Table 1,
entries 15-19). Running the reaction under the argon atmosphere
provided no enhancement to the reaction (Table 1, entry 20).
Finally, the control experiment showed a very low efficient were
achieved in the absence of AgOTf catalyst (Table 1, entry 21). Thus,
the standard reaction conditions was obtained: AgOTf (10 mol%)
as the catalyst, 1.0 equiv HOTf as additive, in 2.0 mL DCE for 0.3
mmol 1-(4-methoxyphenyl)ethanone 1a with 2.5 equiv dimethyl
phosphonate 2a, at 110 oC under an air atmosphere.
Scheme 1 Synthesis of vinylphosphonates compounds.
ro os or
a
on o
a ene
lk
ro os or
a
on o
a
ne
lky
Hyd ph ph yl ti
f
Hyd ph ph yl ti
f
R2
H
R2
H
rans on me a
iti t l
rans on me a
t iti t l
t
,
,
,
R1
P O OR3
)(
u
A
Pd Ni
R1
P O OR3
Pd Ni
(
)
2
(
)(
)
2
O
s wor
Thi
:
k
HP OR3
(
)
2
P O OR3
)(
(
)
2
P O OR3
)(
HO
R2
(
)
2
R2
ew s c
L
i A id
ew s
c
L
i
A id
c
R1
R1
rons e
B
t d A id
H2O
-
os or
a
on o e one
f K t
ro os on
a
on o e one
f K t
Ph ph yl ti
Hyd ph ph yl ti
phosphonates via Lewis acid-catalyzed hydrophosphonylation of
ketones with dimethyl phosphonate, which method was highly
tolerable for functionalized ketones (Scheme 1). Herein, we dis-
close a general and efficient method for the synthesis of vi-
nylphosphonate compounds from ketones with dialkyl phosphate,
via ketone hydrophosphonylation/α-hydroxy phosphonates uni-
molecular elimination (E1) dehydration cascade reaction sequence.
The method benefits from using cheap and easily available mate-
rials, and rea lized in an environmentally friendly and atomic
economy way with the water as the only by-product (Scheme 1).
With the optimal reaction conditions in hand, we then
examined the substrate scope of the reaction. The summary of
1-(4-methoxyphenyl)ethanone 1a reacted with different P-sources
as shown in Scheme 2. The catalytic system worked well with
hydrogen phosphonates such as dimethyl phosphonate, diethyl
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Chin. J. Chem. 2021,39, XXX－XXX

Running title
Chin. J. Chem.
phosphonate,
bis(2,2,2-trifluoroethyl)phosphonate
dibutyl
phosphonate
and
ethyl
straight chain aliphatic ketones and conjugated ketones,
could also generate the desired product in moderate to high
yields with highly stereo-selectivity (Scheme 3, entries
(2aa-2ad),
phenylphosphinate 2e to give the desired products in moderate
yield. Clearly, dialkyl phosphonate substrates showed a significant
higher activity compared with the diphenyl phosphate and
phosphine oxides substrates under standard condition (3ag-3ah).
The other reason may be that the electrophilic phosphorus species
formed by diphenylphosphine oxide in the presence of Tf2O or
HOTf, which was inhibited the reaction.[14]
3va-3za). However, the results show that the regioselectivity
of the product competes with the hydrogen phosphorylation
on C=C bond and C=O bond when cyclohex-2-enone was in-
troduced into reaction under the optimized reaction condi-
tions. Unfortunately, only trace product were obtained when
4- phenylbut-3-yn-2-one was introduced to optimized
reaction conditions (Scheme 3, entry 3aaa).
Scheme 2 Substrate scope of P-sources a,b
Scheme 3 Substrate scope of ketones a,b
O
mo
AgOTf 10
(
l
%
)
O
.
e
u v
R2
P O R3R4
HOTf 1 0
q
i
+
(
)
H
PR3R4
mo
l
%
)
(
)
A
T
1
gO
f
0
O
(
O
P
,
DCE 110 o
C
.
R2
+
e
u v
q
i
e
M
O
Tf2
O
2 5
,
(
E
)
e
H
R1
OC 2C
H
F
M
O
(
)
3
2
R1
P OCH2CF3
( )
2
1
2
D
80 o
C
C
3
1
2
3
n
u
)
2
P O OCH
P O OC2H5
)(
P O
O
)(
B
Cl
(
)(
)
(
)
2
3
2
(
P O OCH CF
)(
P O OCH CF
P O OCH CF
(
)
3
2
2
(
)(
)
2
3
2
(
)(
)
2
3
2
P O OCH CF
P O OCH CF
(
)(
)
(
)(
)
2
3
2
2
3
2
e
e
R
M
O
M
O
e
M
O
R
Cl
,
,
=
=
,
ac
,
e
a
',
,
a
d
86%
,
,
a
,
a
3
83%
j
R
R
3
b
OM
80%
a
3h
aa
=
=
=
=
=
=
=
,
,
c
3
5
3i
8
%
96%
86%
3
3
aa
8
4
%
e
R
R
R
R
R
R
R
OM
3
a
,
86
%
%
%
%
,
c
a
b
H
3
91
,
,
%
r
B
3b 96
,
ca
3
92
3d 88
Cl
,
,
P O Ph
( )
2
P O OC H
n
a
(
)(
)
5
P O B
P O OPh
)(
2
F
P R
O O
( )( )
2
(
)
2
(
)
2
P O OCH CF
P O OCH CF
(
)(
)
2
3
2
,
,
(
)(
)
2
3
2
Ph
ea
H
3
,
99
%
e
e
R1
M
O
M
O
e
M
O
e
O
M
,
a
CF3 3f 94
%
7
,
,
3
,
90%
=
=
=
R1
H
R
e
CH2CF3
=
ma
,
,
c e
,
c
,
c
,
,
,
c
,
,
a
3
l
d
,
81
a
h
r
ace
t
ae
a
a
6
7
%
a
r
ace
3
a
3
k
3
7
6%
3
f
5
N
O2
3g
'
,
40
0%
3
g
t
9
%
,
c
%
R1 OM
R
R
CH2CF3
CH2CH3
ma
3
%
c
,
,
'',
=
=
R1 OM
38
ma
3
e
%
a Reaction conditions: 1 (0.3 mmol), 2 (2.5 equiv), AgOTf (10 mol%), and
P O OCH2CF3
( )( )
2
O
P O OCH CF
P O OCH CF
)(
(
)(
)
2
2
3
(
)
3
2
2
P O OCH CF
b
(
)(
)
2
2
3
HOTf (1.0 equiv) was stirred in DCE (3 mL) at 110°C under air for 15 h.
Yield of the isolated product. c Tf2O (2.5 equiv), 80 °C. d 24 h. e 24 h.
,
c
,
,
c
,
a
7
5%
c
,
c
oa
a
na
3
3
68
3p 99 80
%
%
%
3q
94
%
Ph
We next surveyed the scope of ketone component with
bis (2,2,2-trifluoroethyl) phosphonate 3d (Scheme 3). Only
45% yeild the desired product was obtained when
1-(4-bromophenyl)ethanone was introduced the optimized
condition. We further screened the reaction conditions and
found that when 1.0 equiv of HOTf was replaced by 2.5 equiv
of Tf2O, the yield of the product increased up to 96% yeild
P O OCH CF
)(
(
)
2
2
3
P O OCH CF
P O OCH CF
(
)(
)
(
)(
)
2
3
2
2
3
2
P
E
H
O
OC 2C
F
)
3
2
(
)(
S
e
M
O
,
,
74
,
:
e
,
>
>
d
sa
:
:
ua
3
a
:
ra
3
3
Z
(
E
20 1 72
%
3
t
Z
20 1 71
%
%
68
%
)
(
)
P O OCH CF
(
P O OCH CF
)(
)(
)
2
3
2
(
)
3
2
2
P O OCH CF
(
)(
)
3
2
2
P O OCH CF
)(
(
)
3
2
2
,
,
va
,
wa
75
%
xa
:
)
3
84 4 1
3
80
%
%
3
(
o
and the reaction temperature was decreased to 80 C (see
P O OCH CF
)(
(
)
2
2
3
Cl
supporting information for details). And then we
investagated different substituent on the phenyl ring of
acetophenone, to our delight, both electron-withdrawing or
electron-donating groups were tolerated well under
condition and delivered the desired product in excellent
yields (Scheme 3, entries 3ba-3ia). At the same time, strong
electron withdrawing groups on the phenyl ring of
acetophenone can also obtain excellent yields, such as CF3
Cl
P O OCH CF
)( )
3
2
(
P O OCH CF
)(
2
P O OCH CF
)(
(
)
2
3
2
(
)
2
2
3
,
,
,
a
:
aaa race
3
za
3y 72 10 1
%
(
t
3
47
%
)
a Reaction conditions: 1 (0.3 mmol), 2 (2.5 equiv), AgOTf (10 mol%), and
Tf2O (2.5 equiv) was stirred in DCE (3 mL) at 80°C under air for 15 h. b Yield
of the isolated product. HOTf (1.0 equiv), 110 °C. d HOTf (1.0 equiv), 60 °C.
c
e Al(OTf)3 (10 mol%).
In order to demonstrate the utility of our reaction, firstly, we
tested a large-scale experiment with 5 mmol 3p was used under
the standard reaction conditions, to our delight, 1.46 g of the cor-
responding product 3pa was obtained in the reaction without
siginificant decrease in the yield (A, Scheme 4). In addition, 3aa
was obtained in 75% yield from 1a with trimethyl phosphate un-
der the optimal reaction conditions. Meanwhile, we also demon-
strated that the products of our system could be easily converted
into other derivatives. For example, compound 4aa and
3ma′′could be easily obtained in 93% yield through facile reduc-
tion of the 3aa.[9b] At the same time, inhibitor 5ma′′ is an im-
portant non-steriod anti-flammatory precursors of drug, which
and NO2 (Scheme 3, entries 3fa
the substitution have a minimal effect on the outcome of the
reaction, 3ia 3ka were obtained in a similar yield compared
-3ga). Also, the steric effect of
-
with parent substrate. In addition, 1-acetonaphthone and
2-acetonaphthone could also provide the vinylphosphonate
product 3la-3ma in 67%-90% yields. However, the corre-
sponding products 3ma′-3ma′′ were obtained in moderate
yields when 1-(6-methoxynaphthalen-2-yl)ethanone was
introduced under reaction condition. Furthermore,
chroman-4-one was introduced to the optimization of
reaction conditions and corresponding vinylphosphonate 3ha
was obtained in an excellent yield (94% yield). At the same
time, other benzene fused cyclic ketones 1o-1q could also
reacted with bis (2,2,2-trifluoroethyl) phosphonate to deliver
the desired product in moderate to excellent yields (Scheme
3, entries 3oa-3qa). Moreover, we found that heteroaromatic
ketone can be successfully converted into corresponding
was
synthesized
from
easily
available
material,
1-(6-methoxynaphthalen-2-yl)ethanone 2m (B, Scheme 4).2f
Moreover, α-arylphosphonates derivatives are widely used be-
cause of their interesting biological properties. It has been proven
that Fosmidomycin analogue 5ab' could result in marked increase
in the antimalarial activities (B, Scheme 4). We found that 3ab′ can
be successfully converted into corresponding product Fosmido-
mycin analogue 5ab' in 92% yield.[15]
product 3ra at a much lower temperature. To our delight,
compared
with
HOTf
as
additive,
when
1-(4-methoxyphenyl)-2-phenylethanone 1s
,
1,2- diphe-
nylethanone 1t and 3,4-dihydronaphthalen-2(1H)-one 1u
were applied under Tf2O reaction conditions, the desired
product 3sa, 3ta and 3ua were obtained in 71%-74% yields
with a highly chemo-selective in the system. What’s more,
others substituted aliphatic ketones, such as cyclic ketones,
Chin. J. Chem. 2021,39, XXX－XXX
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First authoret al.
Report
Scheme 4 Gram-scale reaction and application.
AgOTf system, which was detected by insitu HRMS (see supporting
16c]
information),[16b,
then intermediate A was added to
-
:
A
ram ca e eac on
G
S
l
R
ti
O
1-(4-methoxyphenyl)ethanone 1a to generate intermediate B.
Subsequently intermediate C was obtained following facile disso-
ciation in the presence of H+,[16a, 16d, 16e] which was also detected
by insitu HRMS (see supporting information). Finally, the product
3aa was obtained through the unimolecular elimination (E1) de-
hydration of C (Scheme 6).
mo
AgOTf 10
l
%
)
P O OCH CF
)(
(
(
)
2
2
3
O
.
e
u v
q
i
HOTf 1 2
(
)
+
H
P OCH CF
DCE 110 o
C
,
(
)
3
2
2
.
,
,
7
a
mmo
l
)
3p 1 4
6 g 8%
3p
5
(
:
B
ca on
Appli ti
O
mo
l
%
AgOTf 10
(
)
.
e
u v
P O OCH
HOTf 1 2
q
i
(
)(
)
3
2
(
)
+
P OCH
(
DCE 110 o
C
,
)
3
3
e
M
O
e
M
O
,
aa
3
a
1
75
%
Conclusions
P O OCH
)(
(
)
a
P O OCH
( )(
P O OCH
OH
3
2
)
(
)(
)
3
3
2
(
)
b
( )
e
In summary, we have achieved first example of synthesis of
vinylphosphonate from ketones and dialkyl phosphite. Mechanis-
tically, the reaction goes through a Lewis acid promoted ketone
hydrophosphonylation/α-hydroxy phosphonates unimolecular
elimination (E1) dehydration cascade reaction sequence relying on
the advantages of starting from cheap and easily available sub-
strates, as well as producing water as the only byproduct. A series
of vinylphosphonate derivates were synthesized in moderate to
excellent yields.
M
O
e
e
M
O
M
O
,
b
90%
,
a
4
aa
aa
3
4
93%
a
b
( )
P O OEt
P O OEt
OH
(
)
(
)(
)
(
)(
)
2
P O OEt
)(
(
)
2
e
e
O
M
O
M
e
M
O
''
ma
''
,
''
,
ma
3
ma
n
4
90%
5
I
80%
or
.
,
,
CH3OH 70 o
u v
q
i
)
,
hibit
a
b
mo
e
10 Pd/C
%
OH 1 05
9
e
l
HCOONH4 7 5
(
C
%
(
(
)
)
(
)
.
,
,
a
u v
i
N
q
C2H5OH 80 o
C
(
)
OH
HO
P
O
O
s e
t
p
s
6
P O OCH CH
)(
(
)
3
2
2
N
OH
H
3
C
'
b
a
3
',
b
y
a
5
92%
i
osm om c n ana o ue
F
id
l
g
Experimental
To investigate the mechanism of this transformation, the con-
General procedure for the synthesis of vinylphosphonates
General procedure A: An oven-dried 10 mL screw-capped vial
containing 1a (0.3 mmol, 1.0 equiv), AgOTf (0.03 mmol, 0.1 equiv),
and DCE (3 mL) was added via syringe, dimethyl phosphate (0.75
mmol, 2.5 equiv), HOTf (0.3 mmol, 1.0 equiv), and then heated to
110 oC in an oil bath until the starting material has disappeared for
15 hours (monitored by TLC). And then the solvent was removed
in vacuo and residue was purified was purified by column chro-
matography on a short silica gel column using EA/PE as eluent to
afford the desired product 3.
trol experiments were carried out. First, when 2.0 equiv of
2,6-di-tert-butyl-4-methylphenol (BHT) was added in standard
reaction conditions, only 28% of the desired product 3aa was ob-
served (84 % under standard condition), this demonstrated that
the radical process might not be involved in this system (Scheme
5).
Subsequently,
when
dimethyl
(1-hydroxy-1-(4-methoxyphenyl)ethyl) phosphonate 5aa was in-
troduced under standard condition, the desired product 3aa was
detected in 50% yield. This result suggests that dimethyl
(1-hydroxy-1-(4-methoxyphenyl)ethyl) phosphonate 5aa may be
the key intermediate in the reaction (Scheme 5).
General procedure B: An oven-dried 10 mL screw-capped vial
containing 1a (0.3 mmol, 1.0 equiv), AgOTf (0.03 mmol, 0.1 equiv),
and DCE (3 mL) was added via syringe, bis (2,2,2-trifluoroethyl)
phosphonate (0.75 mmol, 2.5 equiv), Tf2O (0.75 mmol, 2.5 equiv),
Scheme 5 Mechanism of the control experiments.
o
and then heated to 80 C in an oil bath until the starting material
O
mo
AgOTf 10
(
l
%
)
.
e
u v
has disappeared for 15 hours (monitored by TLC). And then the
solvent was removed in vacuo and residue was purified was puri-
fied by column chromatography on a short silica gel column using
EA/PE as eluent to afford the desired product 3.
HOTf 1 0
q
i
O
(
)
P O OCH
( )(
,
DCE 110 o
C
)
3
2
+
H
P OCH
(
)
3
2
e
O
M
x e u v
q
i
)
e
BHT
M
O
(
aa
3
e
e
e
a
1
a
2
.
,
,
,
:
u v
BHT 0 5
q
q
q
i
41
45
28
%
%
%
.
u v
1 0
i
.
u v
2 0
i
OH
mo
AgOTf 10
(
l
%
)
Supporting Information
.
P O OCH
e
u v
q
i
)
P O OCH
)(
(
)(
)
HOTf 1 0
3
2
(
)
3
2
(
,
,
5 h
DCE 110 o
C
e
M
O
e
M
O
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2021xxxxx.
,
aa
aa
5
3
5
0%
Scheme 6 Proposed mechanism.
Acknowledgement
OTf
O
a
1
O
O
This work was financially supported by the National Natural
Science Foundation of China (Nos.21762038 and 21968032), the
Fundamental Research Funds for the Central Universities
(31920190077 and 31920190015), the Innovation and
Entrepreneurship Talent Project of Lanzhou (2019-RC-21), the
Scientific Research Foundation of Northwest University for
Nationalities (xbmuyjrc 201603), and the Organic Chemistry
Innovation Groups. The authors thank Dr. Gang-Wei Wang for
helpful discussions.
AgOTf
H
P OCH
(
)
3 2
TfO
P
OC
H
(
)
3 2
P O OCH
HOTf
(
)(
)
3 2
a
2
e
A
S
M O
B
HRM
E I
S
(
H+
)
.
M H + 258 9644
+
[
]
OH
HOTf
-
P O OCH
)
(
)(
3 2
P O OCH
)(
(
)
3 2
H2O
e
M O
e
M O
aa
3
C
HRM
E I
S
)
S
(
.
M H + 261 0894
+
[
]
References
A plausible mechanism is proposed on the basis of our control
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www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021,39, XXX－XXX

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A
(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2021
Manuscript revised: XXXX, 2021
[11] Chen, H.-X.; Huang, L.-J.; Liu, J.-B.; Weng, J.; Lu, G. Synthesis of
Terminal
Vinylphosphonates
Via
Dbu-Promoted
Tandem
Manuscript accepted: XXXX, 2021
Accepted manuscript online: XXXX, 2021
Version of record online: XXXX, 2021
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Radical Hydrophosphorylation of Alkynes with R2P(O)H Generating
www.cjc.wiley-vch.de
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021,39, XXX－XXX

Running title
Chin. J. Chem.
Entry for the Table of Contents
Lewis Acid Enables Ketone Phosphorylation: Synthesis of Alkenyl Phosphonates
Xiao-Hong Wei,*,a Chun-Yuan Bai, a Lian-Biao Zhao, a Ping Zhang, a Zhen-Hua Li, a Yan-Bin Wang a and Qiong Su*,a
Chin. J. Chem.2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX
P
R3R4
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Tf Tf
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A Lewis acid catalyzed cascade reaction of ketone phosphorylation has been developed that enables synthesis of vinylphosphonate derivates in mod-
erate to excellent yields.
Chin. J. Chem. 2021,39, XXX－XXX
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de