Base-promoted selective O-phosphorylation of aryl triflates with P(O)-H compounds

Article abstract of DOI:10.1016/j.tetlet.2020.151971

Compared to previous transition metal-catalyzed C-phosphorylation reactions for constructing C–P bonds, in the absence of transition metal catalysts and ligands, a direct O-phosphorylation of aryl triflates selectively occurred with P(O)-H compounds in the presence of a base via the construction of O–P bonds. This transformation proceeds under simple and mild conditions, and provides a new method for the preparation of valuable organophosphoryl compounds from readily available P(O)-H compounds and triflates.

Full text of DOI:10.1016/j.tetlet.2020.151971

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Base-promoted selective O-phosphorylation of aryl triflates with P(O)-H com‐
pounds
Mingyue Wang, Jia Yang, Shuai Wang, Hong Zhong
PII:
S0040-4039(20)30414-7
DOI:
Reference:
https://doi.org/10.1016/j.tetlet.2020.151971
TETL 151971
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Tetrahedron Letters
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Revised Date:
Accepted Date:
8 March 2020
18 April 2020
21 April 2020
Please cite this article as: Wang, M., Yang, J., Wang, S., Zhong, H., Base-promoted selective O-phosphorylation
of aryl triflates with P(O)-H compounds, Tetrahedron Letters (2020), doi: https://doi.org/10.1016/j.tetlet.
2020.151971
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1
Tetrahedron Letters
journal homepage: www.elsevier.com
Base-promoted selective O-phosphorylation of aryl triflates with P(O)-H
compounds
Mingyue Wang, Jia Yang,* Shuai Wang, Hong Zhong
College of Chemistry and Chemical Engineering, and Hunan Provincial Key Laboratory of Efficient and Clean Utilization of Manganese Resources, Central
South University, Changsha 410083, Hunan, China
 Corresponding author: e-mail: yangjia90@csu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Compared to previous transition metal-catalyzed C-phosphorylation reactions for constructing
C-P bonds, in the absence of transition metal catalysts and ligands, a direct O-phosphorylation
of aryl triflates selectively occurred with P(O)-H compounds in the presence of a base via the
construction of O-P bonds. This transformation proceeds under simple and mild conditions, and
provides a new method for the preparation of valuable organophosphoryl compounds from
readily available P(O)-H compounds and triflates.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Base-promoted
O-phosphorylation
Aryl triflates
P(O)-H compounds
Introduction
triflates can occur and lead to P-O bond construction with P(O)-
H compounds, providing a new method for the synthesis of
Organophosphoryl compounds containing phosphorus-oxygen
bonds are of significant importance in organic synthesis,
materials science, the pharmaceutical industry and biochemistry.1
Traditionally, phosphoryl halides are used as starting materials or
intermediates in the substitution reaction with alcohols for the
synthesis of these compounds; however, in addition to being
toxic, P(O)-X compounds are unstable and thus require a
preparation step.2,3 Recently, cross dehydrogenative coupling
reactions between P(O)-H compounds and alcohols have been
reported for the preparation of these compounds via P-O bond
formation, although these methods require transition-metal
catalysts and the addition of ligands.4 To the best of our
knowledge, efficient and practical methods for the construction
of O-aryl organophosphorus compounds from readily available
and relatively stable P(O)-H compounds are still limited.3-5
useful organophosphoryl compounds (Scheme 1b). Herein, we
report the selective O-phosphorylation reaction of aryl triflates
with P(O)-H compounds under mild conditions.
Previous work
O
P
Z2
O
P
Z2
cat. Ni/ligand
Z1
H
(a)
R O R'
Z1
R
P-C bond formation
R: Ar, Bn, Vinyl
R': Piv, Tf
This work
Ar
O
O
base
Z1
P O Ar
selective O-phosphorylation Z2
Z1
P
Z2
H
(b)
O
Tf
Scheme 1. Base-promoted selective O-phosphorylation of
triflates for organophosphoryl compound synthesis.
The cross coupling reactions of phenol derivatives with P(O)-
H compounds are rarely reported for the construction of P-O
bonds.5 Significant progress has been made in the construction of
P-C bonds via the cross coupling reactions of inert C-O bonds of
phenol derivatives with P-H compounds, using palladium or
nickel catalysts and ligands.6,7 In our previous work, we have
developed several nickel-catalyzed inert C-O/P-H cross-coupling
reactions for P-C bond formation (Scheme 1a).6 As part of our
ongoing work in this area, we serendipitously found that, under
slightly different conditions, selective S-O bond cleavage of aryl
Results and Discussion
We initially explored the model reaction of
diphenylphosphine oxide 2a (0.15 mmol) and phenyl triflate 1a
(0.1 mmol) under Ni-catalyzed conditions. With Ni(COD)2 (5
mol%) and
a base (0.2 mmol), the unexpected phenyl
diphenylphosphinate 3a was formed in 21% yield, in addition to
the typical C-P coupling product (Entry 1). In order to check the
necessity of Ni(COD)2, reactions without the nickel catalyst were
carried out. The reaction of 1a and 2a took place smoothly in the

2
absence of Ni(COD)2 with a 92% yield of 3a (Entry 2), which
indicates the reaction presumably proceeds via a nucleophilic
substitution process. As expected, in the absence of base, no O-P
bond construction occurred (Entry 3). Besides K3PO4, Cs2CO3
and t-BuOLi were also effective bases for the reaction (Entries 4
and 8); however, K2CO3, Na2CO3 and Na3PO4 only gave trace
amounts of the coupling product (Entries 5-7). Decreasing the
amount of K3PO4 led to a decreased yield of 3a (Entries 9-11).
The yield of 3a was improved to 96% by increasing the amount
of K3PO4 to 2.5 equivalents (Entry 12). Different solvents were
also investigated (Entries 14-18). In addition, decreasing or
increasing the temperature from 100 °C resulted in lower yields
(Entries 19-21).
Table 2. Substrate extension for the base-promoted P-O bond
forming reaction. a
O
P
Z2
O
P
K3PO4
Z1
Z2
O
Tf
Z1
H
O
toluene, 100 o
C
R
R
1
2
3
Entry
Substrate 1
Substrate 2
Product 3 (isolated yield)
OP(O)Ph2
OTf
2a
Ph2P(O)H
R
R
1
2
3
4
5
6
7
1a
2a
2a
2a
2a
2a
2a
2a
3a
, R = 4-H, 96%
, R = 4-H
1b, R = 2-Me
3b, R = 2-Me, 91%
1c
3c
, R = 3-Me
, R = 3-Me, 83%
1d, R = 4-Me
3d, R = 4-Me, 85%
Table 1. Base-promoted O-phosphorylation of phenyl triflate.a
1e
3e
, R = 3-MeO
, R = 3-MeO, 87%
3f
, R = 4-MeO, 75%
1f
, R = 4-MeO
O
P
O
P
catalyst, base
Ph
Ph
1g
1h
3g
3h
, R = 4-n-Bu
, R = 4-n-Bu, 81%
Ph
H
O
Tf
O
toluene, 100 oC
8
, R = 4-t-Bu
, R = 4-CF3
, R = 4-CN
2a
2a
2a
2a
2a
2a
, R = 4-t-Bu, 90%
, R = 4-CF3, 89%
, R = 4-CN, 78%
Ph
1a
3a
2a
1i
1j
3i
3j
9
10
11
12
13
1k
3k
, R = 4-F
, R = 4-F, 95%
3l
, R = 4-Cl, 93%
Catalyst
Base
K3PO4
K3PO4
none
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
Yield 3a (%)b
, R = 4-Cl
1l
5 mol% Ni(COD)2
none
21
1m
3m
3n,
, R = 4-Br
, R = 4-Br, 83%
OP(O)Ph2
OTf
92
ND
72
14
2a
none
none
Cs2CO3
K2CO3
Na2CO3
Na3PO4
t-BuOLi
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
1n
52%
none
ND
O
[P]
OTf
none
ND
15b,c
16b,c
17c,d
18c,d
19c,d
1a
3o
3p
2b
2c
2d
2e
2f
, [P] = (4-Me-Ph)2-P(O), 71%
(4-Me-Ph)2-P(O)H
7
none
1a
1a
1a
1a
(2-MeO-Ph)2-P(O)H
, [P] = (2-MeO-Ph)2-P(O), 75%
none
50
n-Bu2P(O)H
3q
, [P] = n-Bu2P(O), 56%
none
25
Ph(EtO)P(O)H
3r
, [P] = Ph(EtO)P(O), 60%
none
37
(i-PrO)2P(O)H
3s
, [P] = (i-PrO)2P(O), 30%
none
60
aReagents and conditions: aryl triflate 1 (0.2 mmol), P(O)-H compound 2 (0.3
none
96
mmol), base (2.5 equiv.), toluene (2 mL), 100 °C, 20 h. b 120 °C. c 3.0 equiv.
d 130 °C.
none
79
none
82
To our delight, both aromatic and aliphatic phosphine oxides
were applicable to the base-promoted O-phosphorylation of aryl
triflates. In addition to diphenylphosphine oxide 2a, bis-(4-
none
Dioxane
DMF
62
none
85
none
Hexane methylphenyl)-p4h3osphine 2b coupled with phenyl triflate 1a to
give the corresponding product 3o in 71% yield (Table 2, entry
15). Bis-(2-methoxyphenyl) phosphine oxide 2c gave 3p in 75%
yield (Entry 16). Meanwhile, aliphatic n-Bu2P(O)H 2d (Entry 17)
reacted with 1a to produce the desired product 3q in 56% yield.
none
CH2Cl2
Toluene
Toluene
Toluene
40
none
83
none
67
none
41
Moreover, hydrogen phosphinate 2e reacted with 1a to give 3r in
a
Reagents and conditions: phenyl triflate 1a (0.1 mmol), Ph2P(O)H 2a (0.15
60% yield (Entry 18), and phosphonate ester 3r was obtained in
30% yield from the reaction between diisopropyl phosphite 2f
and phenyl triflate 1a (Entry 19).
b
mmol), base (0.2 mmol), solvent (1 mL), 100 °C, 20 h. GC yield using
c
d
e
tridecane as an internal standard. 0.5 equiv. base. 1.0 equiv. base. 1.5
equiv. base. f 2.5 equiv. base. g 3.0 equiv. base. h 120 °C. i 80 °C. j 60 °C.
The reaction mixtures were monitored by 31P NMR and 19F
NMR spectroscopy to study the reaction mechanism (Fig. 1). As
indicated by 31P NMR spectroscopy, O-phosphorylation product
3a (δ 27.94 ppm) was mainly obtained, while no signals of
Ph2P(O)K were observed (Fig. 1a, b, Fig. S1). When t-BuOK was
used to promote the reaction of phenyl triflate 1a and
diphenylphosphine oxide 2a, 3a was also observed by 31P NMR
spectroscopy (Fig. S2). Since diphenylphosphine oxide can react
with t-BuOK at room temperature to produce Ph2P(O)K (δ 86.03
ppm) quantitatively (Fig. S2), we speculated that the phosphorus
anion was an intermediate of this base-promoted selective O-
phosphorylation reaction of triflates. Similar transformations
have been reported in the literature.8 As shown in Figure 1c, a
new signal appeared at δ -88.23 ppm in the 19F NMR spectra,
indicating that CF3S(O)OK is a byproduct of this reaction.9a Only
trace amounts of CF3S(O)OK was detected due to the limited
solubility in toluene (Fig. 1c), while in THF, CF3S(O)OK was
more easily observed in the spectrum (Fig. 1d). 9b
With the optimized reaction condition in hand, we further
investigated the substrate scope. As shown in Table 2, a variety
of aryl triflates 1 were coupled with P(O)-H compounds 2 to
produce the corresponding products in moderate to high yields.
The coupling products were formed in 75-91% yield using aryl
triflates bearing electron-donating groups, such as methyl (2-, 3-
and 4-position) (Table 2, entries 2-4) and methoxy (3 and 4-
position, entries 5 and 6), on the benzene ring. Additionally,
triflates with t-Bu or n-Bu groups on the benzene ring were
coupled with diphenylphosphine oxide 2a to give the
corresponding products in 81% and 90% yield, respectively
(Entries
7
and 8). In addition, electron-withdrawing
trifluoromethyl and cyano groups, gave the products 3i and 3j in
high yields (Entries 9 and 10). Also, triflates bearing halide (F, Cl,
Br) substituents reacted smoothly with 2a, affording products 3k-
m in 83-95% yield (Entries 11-13). Naphthyl triflate 1n was also
tolerated and gave the expected product in 52% yield (Entry 14).

3
Appendix A. Supplementary Data
The following are the supplementary data to this article:
Supplementary data 1.
References and notes
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Figure 1. Experiments monitored by NMR spectroscopy: 31P
NMR spectra of the reaction mixtures with reaction times of 2 h
(a) and 20 h (b); 19F NMR spectra of the reaction using toluene (c)
and THF (d) as the solvent, respectively.
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Referring to the experimental results and previous studies in
the literature,5,8 a reasonable mechanism was proposed. As shown
in Scheme 2, P(O)-H compound 2 initially reacts with potassium
phosphate to generate the corresponding phosphorus anion A,
and then undergo nucleophilic attack by A at sulfur to form
intermediate B. Intramolecular migration of phenoxide in adduct
B could produce intermediate C. In the presence of a base,
trifluoromethanesulfinate eliminates from intermediate C to form
potassium trifluoromethanesulfinate and the corresponding
product 3.
O O
O O
Ar O S CF3
K3PO4
-H
Ar O S CF3
O
P
Z2
O
P
1
Z1
H
P
Z1
Z1
O
Z2
Z2
B
2
A
O
K3PO4
SO2CF3
Ar O P Z1
Z2
Ar O P Z1
Z2
O
Y.; Mei, H.; Pan, Y.; Han, J. J. Org. Chem. 2019, 84, 949–956.
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Organometallic Chem. 2016, 820, 120–124.
3
KOS(O)CF3
C
Scheme 2. Proposed reaction mechanism.
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In summary, we have developed a simple and efficient method
for the preparation of O-aryl organophosphorus compounds via
the base-promoted selective O-phosphorylation of aryl triflates
with P(O)-H compounds. This method avoids the use of
transition metal catalysts and ligands, and the starting materials
are readily available. A variety of aryl triflates and hydrogen
phosphoryl compounds can be employed as substrates in this
coupling reaction, making this a practical method for the
synthesis of valuable organophosphoryl compounds.
6401.
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Fluorine Chem. 2007, 128, 851–856. (b) Smyth, L. A.; Phillips, E. M.;
Chan, V. S.; Napolitano, J. G.; Henery, R.; Shekhar, S. J. Org. Chem.
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Declaration of interests
Acknowledgments
Financial support from the National Natural Science
Foundation of China (No. 21902185), the Natural Science
Foundation of Hunan Province (No. 2019JJ50748), and the
Fundamental Research Funds for the Central Universities of
Central South University are gratefully acknowledged.
√
☐ The authors declare that they have no known
competing financial interests or personal
relationships that could have appeared to influence
the work reported in this paper.

4
☐The authors declare the following financial
interests/personal relationships which may be
considered as potential competing interests:
Graphical Abstract
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template box below.
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Highlights:
 A new method for the construction of P-O
bond from P(O)-H compounds is disclosed.
Base-promoted selective O-phosphorylation
of aryl triflates with P(O)-H compounds
Leave this area blank for abstract info.
Mingyue Wang, Jia Yang,* Shuai Wang, Hong Zhong
Previous work:
This work:
selective O-phosphorylation
P-C bond formation
O
O
O
Z1 P Ar
Z2
cat Ni/ligand
base
Z1 P O Ar
Z1 P H
Z2
Ar O Tf
toluene, T, 20 h
Z2
Z1, Z2 = aryl, alkyl, alkoxyl
30-96% yield
 This selective O-phosphorylation of triflates
proceeds smoothly with a lone base.
 Various O-aryl phosphorus compounds can be
prepared in good to high yields.