Direct synthesis of ortho-halogenated arylphosphonates via a three-component reaction involving arynes

Article abstract of DOI:10.1021/acs.joc.1c00550

A three-component reaction involving arynes, trialkyl phosphites, and halides has been achieved under mild reaction conditions. This transformation provides a direct synthetic approach to ortho-halogenated arylphosphonates, which could be rapidly converted to diversely ortho-functionalized arylphosphorus com ounds

Full text of DOI:10.1021/acs.joc.1c00550

pubs.acs.org/joc
Note
Direct Synthesis of ortho-Halogenated Arylphosphonates via a
Three-Component Reaction Involving Arynes
Yuanting Huang, Yifan Hu, Yukun Han, Yingcong Ou, Yanping Huo, Xianwei Li, and Qian Chen*
Cite This: J. Org. Chem. 2021, 86, 7010−7018
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A three-component reaction involving arynes,
trialkyl phosphites, and halides has been achieved under mild
reaction conditions. This transformation provides a direct synthetic
approach to ortho-halogenated arylphosphonates, which could be
rapidly converted to diversely ortho-functionalized arylphosphorus
compounds.
rylphosphorus compounds are of great importance for
ligands, high temperatures, or long reaction times are generally
required for the reaction conditions. Thus, the development of
a mild and efficient synthetic protocol for the preparation of
ortho-functionalized arylphosphorus compounds is highly
desirable.
A
organic synthesis,1 material chemistry,2 and medicinal
chemistry.3 In particular, ortho-substituents on the phenyl ring
are useful fragments for phosphine ligands and other
applications.4 For example, dialkylbiaryl phosphines are
known as Buchwald-type phosphine ligands, which become
air stable due to the presence of sterically hindered ortho-
substituents.5 These arylphosphorus compounds can typically
be synthesized via the addition of n-butyllithium to ortho-
functionalized aryl halides followed by quenching with
phosphorus electrophiles (Scheme 1a, up).6 An alternative
Arynes including benzyne have been of particular interest
due to their high reactivity and broad applications in organic
synthesis.9,10 Notably, aryne chemistry has been widely utilized
in constructing aryl C−P bonds under mild reaction
conditions, providing various arylphosphorus compounds
with good efficiency.11 Three-component reactions involving
arynes, which mainly include the initial addition of
nucleophiles to arynes and subsequent trapping of the aryl
anion intermediate with electrophiles, enable the rapid
assembly of 1,2-disubstituted arenes with ample structural
diversification.9,12 However, three-component reactions of
arynes, phosphorus nucleophiles, and other electrophiles
have received less attention, and the employment of
phosphorus nucleophiles and the electrophilic components is
limited to tertiary phosphines and carbonyl compounds.13 It is
noteworthy that Wittig and co-workers have reported a series
of work on the ortho-difunctionalization reaction of arynes and
organophosphorus compounds.14 With the above background
and our recent studies on phosphorylation reactions,15 we
became interested in developing a novel three-component
reaction of arynes, phosphorus nucleophiles, and halogen
electrophiles12a−e for accessing ortho-halogenated arylphos-
phorus compounds, which could be rapidly converted to
diversely ortho-functionalized arylphosphorus compounds.1b−e
To the best of our knowledge, this type of reaction has never
Scheme 1. Synthesis of ortho-Functionalized
Arylphosphorus Compounds
method employs Pd-, Cu-, or Ni-catalyzed Hirao reaction of
these aryl halides with phosphorus nucleophiles (Scheme 1a,
down).7 Noteworthily, the direct ortho-functionalization of
arylphosphorus compounds using the strategy of transition-
metal-catalyzed aryl C−H activation has been well-docu-
mented over the past decade.8 However, previous methods are
often limited by the availability of the starting materials. In
addition, strong bases, transition-metal catalysts, expensive
Received: March 8, 2021
Published: April 21, 2021
https://doi.org/10.1021/acs.joc.1c00550
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 7010−7018
7010

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
been reported. Herein, we describe a direct approach for the
synthesis of ortho-halogenated arylphosphonates through a
three-component reaction of silylaryl triflates as aryne
precursors,16 trialkyl phosphites, and halides under mild
reaction conditions (Scheme 1b).
when the reaction was performed at 80 or 40 °C (entries 11
and 12). In addition, the reaction using CHCl3 or NCS instead
of CCl4 as the chlorine source failed to give the corresponding
4a.
Aryl iodides or bromides are typically employed for the
transition-metal-catalyzed cross-coupling reactions, while aryl
chlorides are usually unreactive under mild reaction con-
ditions.1b−e We then turned to screening of halogen sources to
prepare other halogenated arylphosphonates. As shown in
Table 2, the employment of CBr4, NBS, CCl3Br, or CBr3F
According to our recent studies on P-arylation of dialkyl
phosphites and secondary phosphine oxides with arynes,15a,b
we first examined the three-component reaction of commer-
cially available benzyne precursor 1a, diethyl phosphite or
diphenylphosphine oxide (3.0 equiv), and CCl4 (15 equiv) in
the presence of CsF (3.0 equiv) and 4 Å molecular sieves in
anhydrous CH3CN at 65 °C. Unfortunately, only the direct P-
arylation products formed by the protonation of the aryl anion
intermediates15a were observed probably due to the acidic
hydrogen atoms of R2P(O)H. Inspired by Mhaske’s pioneering
research,17 triethyl phosphite 2a containing no acidic hydrogen
atoms was then employed as the phosphorus nucleophile, and
a range of reaction conditions were investigated as shown in
Table 1. To our delight, the reaction afforded the desired
a
Table 2. Screening of Halogen Sources
entry
3 (equiv)
product (yield)
b
1
CBr4 (3)
NBS (3)
5a (0%)
5a (0%)
5a (0%)
5a (0%)
5a (62%)
6a (35%)
6a (0%)
6a (0%)
a
Table 1. Optimization of the Reaction Conditions
2
3
4
CCl3Br (15)
CBr3F (15)
CHBr3 (15)
CHI3 (3)
NIS (3)
b
5
b
6
7
8
I2 (3)
entry
fluoride
base
solvent
yield of 4a (%)
a
b
Reaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), 3 (3 or 15
1
CsF
CsF
KF
KF
KF
KF
KF
KF
KF
KF
KF
KF
CH3CN
CH3CN
CH3CN
THF
27
39
45
33
30
27
32
56
76
80
48
0
equiv), KF (0.6 mmol), 18-crown-6 (0.6 mmol), K3PO4 (0.2 mmol),
2
3
4
5
6
7
8
4 Å MS (100 mg), CH3CN (2 mL), 65 °C, 24 h. Isolated yield based
b
on 2a. K3PO4 was replaced by DBU.
DCE
failed to give the desired ortho-bromophenylphosphonate 5a
(entries 1−4), while the use of CHBr3 as the bromine source
smoothly afforded 5a in 62% yield in the presence of DBU
instead of K3PO4 (entry 5). Similarly, ortho-iodophenyl-
phosphonate 6a was obtained in 35% yield with the use of
CHI3 as the iodine source (entry 6), and the employment of
NIS or molecular I2 failed to give 6a (entries 7 and 8).
Cs2CO3
K2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
c
9
d
10
11
12
de
,
df
,
a
With the optimized reaction conditions in hand, we then set
out to explore the generality of the three-component reaction.
We first applied the optimized conditions (Table 1, entry 10)
to the synthesis of ortho-chloroarylphosphonates via the
coupling of a variety of aryne precursors 1, trialkyl phosphites
2, and CCl4, and the results were illustrated in Table 3.
Pleasingly, the reactions of benzyne (generated from 1a) with
various trialkyl phosphites 2 and CCl4 led to the formation of
ortho-chloroarylphosphonates 4a−4e in 42−80% isolated
yields. We also tried the reactions with the use of other P(III)
nucleophiles such as dimethyl phenylphosphonite 2f and ethyl
diphenylphosphinite 2g, while both reactions failed to give the
desired 4f and 4g. In addition, 2f and 2g were oxidized to give
dimethyl phenylphosphonate and ethyl diphenylphosphinate,
respectively. The employment of other symmetric arynes
(generated from 1b and 1c) afforded 4h and 4i in good yields.
We then turned to unsymmetric arynes, and 3-methoxy-
substituted aryne (generated from 1d) reacted cleanly with
triethyl phosphite and CCl4 to generate 4j as a single isomer,
which was in good agreement with the regioselectivity reported
in the literature.18 The employment of unsymmetric 4-
substituted arynes (generated from 1e−1g) bearing different
groups (Me, OMe and OCF3) produced 4k/4k′−4m/4m′ in
55−63% yields with two regioisomers, which further suggested
Reaction conditions: 1a (0.2 mmol), 2a (0.6 mmol), 3a (3 mmol),
fluoride (0.6 mmol), 18-crown-6 (0.6 mmol), base (0.2 mmol), 4 Å
b
MS (100 mg), solvent (2 mL), 65 °C, 24 h. Isolated yield. The
c
reaction was performed without 18-crown-6. 0.3 mmol of 1a and 0.2
d
mmol of 2a were employed. 0.4 mmol of 1a and 0.2 mmol of 2a
e
f
were employed. The reaction was performed at 80 °C. The reaction
was performed at 40 °C.
diethyl ortho-chlorophenylphosphonate 4a in 27% isolated
yield (entry 1), together with the protonated product diethyl
phenylphosphonate17 in 40% yield. With the use of 18-crown-6
(3.0 equiv) and KF instead of CsF, the desired 4a was isolated
in 45% yield (entries 2 and 3). A simple screening of solvents
was then carried out (entries 4 and 5), and CH3CN was
proved to be the optimum solvent. When an inorganic base
was introduced into the reaction (entries 6−8), the yield of 4a
increased to 56% in the presence of K3PO4 probably due to the
neutralization of HCl generated by CCl4 or other acidic
protons with bases (entry 8). Pleasingly, when the reaction was
carried out with excess amounts of benzyne precursor 1a (1.5
or 2.0 equiv), the yield of 4a significantly increased to 76%
(entry 9) or 80% (entry 10). It is noteworthy that only trace
amounts of the protonated product were detected in the
reaction (entry 10). The product yield significantly decreased
7011
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
a
Table 3. Synthesis of ortho-Chloroarylphosphonates
Table 4. Synthesis of ortho-Bromoarylphosphonates and
ortho-Iodophenylphosphonates
a
a
Reaction conditions: 1 (0.4 mmol), 2 (0.2 mmol), 3 (3 mmol of
CHBr3 or 0.6 mmol of CHI3), KF (0.6 mmol), 18-crown-6 (0.6
mmol), DBU (0.2 mmol), 4 Å MS (100 mg), CH3CN (2 mL), 65 °C,
b
24 h. Isolated yield based on 2. The yield includes both major isomer
5i and minor isomer 5i′. The ratio was determined by 31P{1H} NMR.
employed. In addition, silylaryl triflate 1h underwent this
reaction efficiently, delivering 5i/5i′ (4:1) in 51% yield.
Moreover, the reaction of benzyne, triethyl or trimethyl
phosphite, and CHI3 afforded ortho-iodophenylphosphonates
6a and 6b in 35% and 33% yields, respectively.
To show the synthetic utility of our method, a scale-up
experiment and transformation of the resultant product were
conducted (Scheme 2). A gram-scale reaction of 2a (1.33 g,
8.0 mmol) with 1a (16 mmol) and CCl4 (120 mmol) was
conducted under the standard conditions, and the desired 4a
was isolated in 52% yield (1.03 g). The reaction of ortho-
bromophenylphosphonate 5a with PhSnBu3 resulted in the
Scheme 2. Gram-Scale Synthesis and Synthetic Application
a
Reaction conditions: 1 (0.4 mmol), 2 (0.2 mmol), 3a (3 mmol), KF
(0.6 mmol), 18-crown-6 (0.6 mmol), K3PO4 (0.2 mmol), 4 Å MS
(100 mg), CH3CN (2 mL), 65 °C, 24 h. Isolated yield based on 2.
b
The yield includes both major isomer 4 and minor isomer 4′. The
ratio was determined by 31P{1H} NMR.
that an aryne intermediate was involved in the reaction.
Noteworthily, bulky 1,2-didehydronaphthalene (generated
from 1h) was also applicable to the reaction, leading to the
formation of the desired 4n/4n′ (7:1) in 74% yield.
Next, the synthesis of ortho-bromoarylphosphonates and
ortho-iodoarylphosphonates was carried out under the
optimized conditions (Table 2, entry 5 or 6), and the results
were illustrated in Table 4. The coupling of symmetric arynes,
various trialkyl phosphites, and CHBr3 provided ortho-
bromoarylphosphonates 5a−5g in 55−63% isolated yields.
The desired 5h was also obtained in 40% yield as a single
isomer when the unsymmetric aryne precursor 1d was
7012
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
doublet; t = triplet, dd = doublet of doublets, m = multiplet, dt =
double of triplets. The known compounds 4a,20 4b,21 4c,22 4d,23 5a,24
5b,4e 5c,25 5i,26 6a,27 7a,28 7b,29 and 7c30 showed characterization
data in full agreement with previously reported data.
General Procedure for the Synthesis of Compounds 4. To a
solution of 2-(trimethylsilyl)-phenyl triflate 1a (119 mg, 0.4 mmol),
triethyl phosphite 2a (33 mg, 0.2 mmol), and CCl4 3a (462 mg, 3.0
mmol) in acetonitrile (2 mL) were added K3PO4 (42 mg, 0.2 mmol),
KF (35 mg, 0.6 mmol), 18-crown-6 (159 mg, 0.6 mmol), and 4 Å
molecular sieves (100 mg). The mixture was stirred in an oil bath at
65 °C for 24 h. After removal of the solvent, the residue was then
purified by flash column chromatography on silica gel with petroleum
ether/ethyl acetate (4:1) to give the pure product 4a (40 mg, 80%) as
a yellow oil.
General Procedure for the Synthesis of Compounds 5. To a
solution of 2-(trimethylsilyl)-phenyl triflate 1a (119 mg, 0.4 mmol),
triethyl phosphite 2a (33 mg, 0.2 mmol), and CHBr3 3b (756 mg, 3.0
mmol) in acetonitrile (2 mL) were added DBU (31 mg, 0.2 mmol),
KF (35 mg, 0.6 mmol), 18-crown-6 (159 mg, 0.6 mmol), and 4 Å
molecular sieves (100 mg). The mixture was stirred in an oil bath at
65 °C for 24 h. After removal of the solvent, the residue was then
purified by flash column chromatography on silica gel with petroleum
ether/ethyl acetate (4:1) to give the pure product 5a (36 mg, 62%) as
a yellow oil.
Stille coupling, leading to the formation of biarylphosphonate
7a in 65% yield. Furthermore, both the Hiyama coupling of 5a
with PhSi(OEt)3 and the Suzuki coupling of 5a with
PhB(OH)2 smoothly afforded 7a in good yields. We then
turned to the Heck coupling, and the reaction of 5a with
methyl acrylate led to the desired 7b in 70% yield. In addition,
the cyanation of 5a with CuCN gave ortho-cyanophenyl-
phosphonate 7c in 56% yield.
Based on the above experimental results and previous
reports,12,13,17 a plausible main reaction pathway for the
formation of 4a is outlined in Scheme 3. Benzyne, which is
Scheme 3. Proposed Mechanism
General Procedure for the Synthesis of Compounds 6. To a
solution of 2-(trimethylsilyl)-phenyl triflate 1a (119 mg, 0.4 mmol),
triethyl phosphite 2a (33 mg, 0.2 mmol), and CHI3 3c (236 mg, 0.6
mmol) in acetonitrile (2 mL) were added DBU (31 mg, 0.2 mmol),
KF (35 mg, 0.6 mmol), 18-crown-6 (159 mg, 0.6 mmol), and 4 Å
molecular sieves (100 mg). The mixture was stirred in an oil bath at
65 °C for 24 h. After removal of the solvent, the residue was then
purified by flash column chromatography on silica gel with petroleum
ether/ethyl acetate (4:1) to give the pure product 6a (24 mg, 35%) as
a yellow oil.
generated by fluoride-induced elimination of benzyne
precursor 1a, suffers a nucleophilic attack of triethyl phosphite
to produce the 1,3-zwitterionic intermediate 8, which is
trapped by CCl4 to form the intermediate 9. The product 4a is
then obtained via subsequent Michaelis−Arbuzov type of
mechanism19 involving the participation of a fluoride ion or
others. In addition, the formation of 5 and 6 could possibly be
explained by the similar pathway of the formation of 4a.
In conclusion, we have developed a novel three-component
reaction of arynes with the use of a trialkyl phosphite as the
nucleophile and a halide as the electrophile to prepare ortho-
halogenated arylphosphonates in moderate to good yields
under mild reaction conditions. The resultant products could
be further used in organic synthesis and transformed into other
ortho-functionalized arylphosphorus compounds. The good
functional group compatibility and mild reaction conditions
showcase the potential of this approach in chemical synthesis.
Gram-Scale Synthesis. To a solution of 2-(trimethylsilyl)-phenyl
triflate 1a (4.77 g, 16 mmol), triethyl phosphite 2a (1.33 g, 8.0
mmol), and CCl4 3a (18.46 g, 120 mmol) in acetonitrile (80 mL)
were added K3PO4 (1.70 g, 8.0 mmol), KF (1.39 g, 24 mmol), 18-
crown-6 (6.34 g, 24 mmol), and 4 Å molecular sieves (4.0 g). The
mixture was stirred in an oil bath at 65 °C for 48 h. After removal of
the solvent, the residue was then purified by flash column
chromatography on silica gel with petroleum ether/ethyl acetate
(4:1) to give the pure product 4a (1.03 g, 52%) as a yellow oil.
Synthetic Application (The Stille Coupling). A mixture of
diethyl (2-bromophenyl)phosphonate 5a (59 mg, 0.2 mmol),
tributylphenyltin (88 mg, 0.24 mmol), Pd(OAc)2 (1.4 mg, 0.006
mmol), DABCO (1.4 mg, 0.012 mmol), and TBAF (157 mg, 0.6
mmol) in 1,4-dioxane (2 mL) was taken under argon atmosphere in a
sealed tube vial. The mixture was stirred in an oil bath at 100 °C for
24 h. After removal of the solvent, the residue was then purified by
flash column chromatography on silica gel with petroleum ether/ethyl
acetate (4:1) to give the pure product 7a (38 mg, 65%) as a yellow oil.
Synthetic Application (The Hiyama Coupling). A mixture of
diethyl (2-bromophenyl)phosphonate 5a (59 mg, 0.2 mmol),
phenyltriethoxysilane (96 mg, 0.4 mmol), Pd(OAc)2 (1.4 mg, 0.006
mmol), DABCO (1.4 mg, 0.012 mmol), and TBAF (104 mg, 0.4
mmol) in 1,4-dioxane (2 mL) was taken under argon atmosphere in a
sealed tube vial. The mixture was stirred in an oil bath at 80 °C for 24
h. After removal of the solvent, the residue was then purified by flash
column chromatography on silica gel with petroleum ether/ethyl
acetate (4:1) to give the pure product 7a (43 mg, 74%) as a yellow oil.
Synthetic Application (The Suzuki Coupling). A mixture of
diethyl (2-bromophenyl)phosphonate 5a (59 mg, 0.2 mmol),
phenylboronic acid (36 mg, 0.3 mmol), Pd(PPh3)4 (23 mg, 0.02
mmol), and Na2CO3 (42 mg, 0.4 mmol) in toluene/water/ethanol
(5/5/1, 2 mL) was taken under argon atmosphere in a sealed tube
vial. The mixture was stirred in an oil bath at 100 °C for 24 h. The
reaction mixture was then extracted with ethyl acetate (10 mL) for
three times, dried over Na2SO4, and concentrated under reduced
pressure. The residue was then purified by flash column
EXPERIMENTAL SECTION
■
General Details. Unless otherwise stated, commercially available
reagents including dry solvents were used without additional
purification. Acetonitrile was distilled from calcium hydride. THF
was distilled from sodium. Petroleum ether refers to the petroleum
fraction bp 40−90 °C. Commercial reagents were used without
purification unless otherwise noted. Kobayashi’s aryne precursors 1
which were not commercially available were prepared according to
the literature.16 Flash chromatography was performed using the
indicated solvent system on silica gel standard grade (200−300
1
mesh). H NMR spectra were recorded in CDCl3 on a Bruker 400
(400 MHz) spectrometer. 13C{1H} NMR spectra were recorded in
CDCl3 on a Bruker 400 (100 MHz) spectrometer. 31P{1H} NMR
spectra were recorded in CDCl3 on a Bruker 400 (162 MHz)
spectrometer. 19F{1H} NMR spectra were recorded in CDCl3 on a
Bruker 400 (376 MHz) spectrometer. Chemical shifts are reported
1
relative to CDCl3 (δ 7.26 ppm) for H NMR and CDCl3 (δ 77.0
ppm) for 13C{1H} NMR. High-resolution mass spectra (HRMS) were
recorded on a Q-Exactive Orbitrap mass spectrometer (Thermo, CA).
Abbreviations for signal coupling are as follows: s = singlet, d =
7013
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1
chromatography on silica gel with petroleum ether/ethyl acetate (4:1)
to give the pure product 7a (49 mg, 85%) as a yellow oil.
4/1 as the eluent); H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 14.0
Hz, 1H), 7.30 (d, J = 5.1 Hz, 1H), 4.23−4.05 (m, 4H), 2.95−2.88 (m,
4H), 2.15−2.08 (m, 2H), 1.35 (t, J = 7.0 Hz, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 151.1 (d, J = 2.9 Hz), 142.8 (d, J = 14.3 Hz),
134.4 (d, J = 3.6 Hz), 131.7 (d, J = 8.3 Hz), 126.7 (d, J = 11.6 Hz),
124.2 (d, J = 191 Hz), 62.3 (d, J = 5.4 Hz), 33.0, 32.1, 25.4, 16.3 (d, J
= 6.6 Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 16.0; HRMS (ESI-
Orbitrap) m/z: [M + H]+ calcd for C13H1935ClO3P 289.0755, found
289.0750.
Synthetic Application (The Heck Coupling). A mixture of
diethyl (2-bromophenyl)phosphonate 5a (59 mg, 0.2 mmol), methyl
acrylate (35 mg, 0.4 mmol), Pd(PPh3)4 (23 mg, 0.02 mmol), and
Na2CO3 (42 mg, 0.4 mmol) in DMA (2 mL) was taken under argon
atmosphere in a sealed tube vial. The mixture was stirred in an oil
bath at 100 °C for 24 h. After the addition of water (5 mL) to the
reactant, the mixture was then extracted with ethyl acetate (10 mL)
five times, dried over Na2SO4, and concentrated under reduced
pressure. The residue was then purified by flash column
chromatography on silica gel with petroleum ether/ethyl acetate
(4:1) to give the pure product 7b (42 mg, 70%) as a yellow oil.
Synthetic Application (Cyanation). To a solution of diethyl (2-
bromophenyl)phosphonate 5a (59 mg, 0.2 mmol) in DMF (2 mL)
was added CuCN (28 mg, 0.3 mmol). The mixture was stirred in an
oil bath at reflux for 16 h. After the addition of water (5 mL) to the
reactant, the mixture was then extracted with ethyl acetate (10 mL)
five times, dried over Na2SO4, and concentrated under reduced
pressure. The residue was then purified by flash column
chromatography on silica gel with petroleum ether/ethyl acetate
(4:1) to give the pure product 7c (27 mg, 56%) as a yellow oil.
Diethyl (2-Chlorophenyl)phosphonate (4a).20 Yellow oil (40 mg,
80%); Rf = 0.24 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.03−7.97 (m, 1H), 7.47−7.44 (m,
2H), 7.38−7.32 (m, 1H), 4.25−4.08 (m, 4H), 1.35 (t, J = 7.0 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 136.8 (d, J = 3.0 Hz),
135.9 (d, J = 7.8 Hz), 133.5 (d, J = 2.6 Hz), 130.7 (d, J = 10.3 Hz),
127.4 (d, J = 190 Hz), 126.4 (d, J = 13.7 Hz), 62.5 (d, J = 5.5 Hz),
16.3 (d, J = 6.5 Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 14.5.
Dimethyl (2-Chlorophenyl)phosphonate (4b).21 Yellow oil (34
mg, 78%); Rf = 0.22 (petroleum ether/ethyl acetate = 4/1 as the
Diethyl (2-Chloro-4,5-dimethylphenyl)phosphonate (4i). Yellow
oil (34 mg, 61%); Rf = 0.25 (petroleum ether/ethyl acetate = 4/1 as
the eluent); H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 14.3 Hz,
1H), 7.22 (d, J = 5.6 Hz, 1H), 4.22−4.03 (m, 4H), 2.26 (s, 3H), 2.27
(s, 3H), 1.33 (t, J = 7.1 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 143.3 (d, J = 2.8 Hz), 137.0 (d, J = 8.4 Hz), 135.2 (d, J = 13.9 Hz),
133.6 (d, J = 2.9 Hz), 131.6 (d, J = 11.0 Hz), 123.8 (d, J = 192 Hz),
62.3 (d, J = 5.4 Hz), 19.7, 19.0, 16.3 (d, J = 6.6 Hz); 31P{1H} NMR
(162 MHz, CDCl3) δ 15.6; HRMS (ESI-Orbitrap) m/z: [M + H]+
calcd for C12H1935ClO3P 277.0755, found 277.0751.
1
Diethyl (2-Chloro-6-methoxyphenyl)phosphonate (4j). Yellow oil
(29 mg, 53%); Rf = 0.31 (petroleum ether/ethyl acetate = 4/1 as the
eluent); H NMR (400 MHz, CDCl3) δ 7.36−7.32 (m, 1H), 7.07−
1
7.04 (m, 1H), 6.87−6.84 (m, 1H), 4.27−4.13 (m, 4H), 3.88 (d, J =
1.4 Hz, 3H), 1.36 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 163.3 (d, J = 3.0 Hz), 138.1 (d, J = 4.2 Hz), 137.4 (d, J =
9.2 Hz), 118.6 (d, J = 198 Hz), 116.6 (d, J = 11.2 Hz), 112.0 (d, J =
14.5 Hz), 62.3 (d, J = 5.3 Hz), 55.6, 16.3 (d, J = 6.6 Hz); 31P{1H}
NMR (162 MHz, CDCl3) δ 13.0; HRMS (ESI-Orbitrap) m/z: [M +
H]+ calcd for C11H1735ClO4P 279.0548, found 279.0544.
Diethyl (2-Chloro-4-methylphenyl)phosphonate (4k). Yellow oil
(16 mg, 31%); Rf = 0.32 (petroleum ether/ethyl acetate = 4/1 as the
eluent); H NMR (400 MHz, CDCl3) δ 7.84 (dd, J = 14.0, 7.8 Hz,
1H), 7.23 (d, J = 5.2 Hz, 1H), 7.12−7.09 (m, 1H), 4.19−4.02 (m,
4H), 2.33 (s, 3H), 1.30 (t, J = 7.1 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 144.6 (d, J = 2.7 Hz), 136.5 (d, J = 3.4 Hz), 135.8 (d,
J = 8.1 Hz), 131.2 (d, J = 10.7 Hz), 127.1 (d, J = 14.0 Hz), 124.0 (d, J
= 193 Hz), 62.3 (d, J = 5.5 Hz), 21.1, 16.2 (d, J = 6.6 Hz); 31P{1H}
NMR (162 MHz, CDCl3) δ 15.2; HRMS (ESI-Orbitrap) m/z: [M +
H]+ calcd for C11H1735ClO3P 263.0598, found 263.0596.
1
1
eluent); H NMR (400 MHz, CDCl3) δ 8.01−7.94 (m, 1H), 7.49−
7.45 (m, 2H), 7.38−7.32 (m, 1H), 3.81 (d, J = 11.4 Hz, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 136.8 (d, J = 3.0 Hz), 137.0 (d,
J = 7.8 Hz), 133.8 (d, J = 2.6 Hz), 130.8 (d, J = 10.4 Hz), 126.4 (d, J
= 13.8 Hz), 126.3 (d, J = 192 Hz), 52.9 (d, J = 5.7 Hz); 31P{1H}
NMR (162 MHz, CDCl3) δ 17.6.
Diisopropyl (2-Chlorophenyl)phosphonate (4c).22 Yellow oil (23
mg, 42%); Rf = 0.30 (petroleum ether/ethyl acetate = 4/1 as the
Diethyl (2-Chloro-5-methylphenyl)phosphonate (4k′). Yellow oil
1
eluent); H NMR (400 MHz, CDCl3) δ 8.06−7.98 (m, 1H), 7.43−
(16 mg, 31%); Rf = 0.35 (petroleum ether/ethyl acetate = 4/1 as the
1
7.40 (m, 2H), 7.34−7.28 (m, 1H), 4.76−4.64 (m, 2H), 1.37 (d, J =
6.2 Hz, 6H), 1.24 (d, J = 6.2 Hz, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 136.7 (d, J = 2.7 Hz), 135.9 (d, J = 8.0 Hz), 133.2 (d, J =
2.7 Hz), 130.6 (d, J = 10.2 Hz), 128.7 (d, J = 190 Hz), 126.2 (d, J =
13.8 Hz), 71.3 (d, J = 5.7 Hz), 24.0 (d, J = 4.3 Hz), 23.6 (d, J = 4.9
Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 12.0.
eluent); H NMR (400 MHz, CDCl3) δ 7.82 (dd, J = 14.6, 2.1 Hz,
1H), 7.32 (dd, J = 8.2, 5.6 Hz, 1H), 7.26−7.25 (m, 1H), 4.24−4.05
(m, 4H), 2.35 (s, 3H), 1.34 (t, J = 7.1 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 136.6 (d, J = 8.3 Hz), 136.4, 134.3 (d, J = 2.7 Hz),
133.6 (d, J = 2.9 Hz), 130.5 (d, J = 10.8 Hz), 126.7 (d, J = 189 Hz),
62.4 (d, J = 5.5 Hz), 20.7, 16.3 (d, J = 6.6 Hz); 31P{1H} NMR (162
MHz, CDCl3) δ 15.0; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd
for C11H1735ClO3P 263.0598, found 263.0596.
Diethyl (2-Chloro-4-methoxyphenyl)phosphonate (4l). Yellow oil
(26 mg, 46%); Rf = 0.33 (petroleum ether/ethyl acetate = 4/1 as the
eluent); H NMR (400 MHz, CDCl3) δ 7.92 (dd, J = 13.7, 8.6 Hz,
1H), 6.98 (dd, J = 4.6, 2.4 Hz, 1H), 6.85 (dt, J = 8.6, 2.5 Hz, 1H),
4.20−4.05 (m, 4H), 3.84 (s, 3H), 1.33 (t, J = 7.0 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 163.3 (d, J = 3.0 Hz), 138.1 (d, J = 4.2
Hz), 137.4 (d, J = 9.2 Hz), 118.6 (d, J = 198 Hz), 116.6 (d, J = 11.2
Hz), 112.0 (d, J = 14.6 Hz), 62.3 (d, J = 5.3 Hz), 55.6, 16.3 (d, J = 6.6
Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 15.5; HRMS (ESI-
Orbitrap) m/z: [M + H]+ calcd for C11H1735ClO4P 279.0548, found
279.0544.
Diethyl (2-Chloro-4-(trifluoromethoxy)phenyl)phosphonate
(4m). Yellow oil (34 mg, 50%); Rf = 0.21 (petroleum ether/ethyl
acetate = 4/1 as the eluent); 1H NMR (400 MHz, CDCl3) δ 8.05 (dd,
J = 13.9, 8.5 Hz, 1H), 7.33−7.31 (m, 1H), 7.21−7.18 (m, 1H), 4.26−
4.08 (m, 4H), 1.35 (t, J = 7.1 Hz, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 152.3 (d, J = 1.9 Hz), 138.3 (d, J = 3.9 Hz), 137.4 (d, J =
9.0 Hz), 126.2 (d, J = 194 Hz), 122.7 (d, J = 11.0 Hz), 120.2 (q, JC−F
= 260 Hz), 118.1 (d, J = 15.2 Hz), 62.8 (d, J = 5.6 Hz), 16.2 (d, J =
6.4 Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 13.0; 19F{1H} NMR
Dibutyl (2-Chlorophenyl)phosphonate (4d).23 Yellow oil (37 mg,
60%); Rf = 0.33 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.04−7.96 (m, 1H), 7.47−7.45 (m,
2H), 7.37−7.32 (m, 1H), 4.18−3.99 (m, 4H), 1.72−1.63 (m, 4H),
1.46−1.36 (m, 4H), 0.91 (t, J = 7.4 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 136.8 (d, J = 2.9 Hz), 136.0 (d, J = 7.9 Hz), 133.5 (d,
J = 2.6 Hz), 130.7 (d, J = 10.3 Hz), 127.4 (d, J = 191 Hz), 126.3 (d, J
= 13.7 Hz), 66.2 (d, J = 5.9 Hz), 32.4 (d, J = 6.6 Hz), 18.7, 13.6;
31P{1H} NMR (162 MHz, CDCl3) δ 14.8.
1
Dihexyl (2-Chlorophenyl)phosphonate (4e). Yellow oil (38 mg,
52%); Rf = 0.35 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.03−7.96 (m, 1H), 7.47−7.43 (m,
2H), 7.36−7.31 (m, 1H), 4.16−3.99 (m, 4H), 1.68 (dt, J = 14.6, 6.7
Hz, 4H), 1.40−1.33 (m, 4H), 1.29−1.25 (m, 8H), 0.86 (t, J = 7.0 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 136.8 (d, J = 3.0 Hz),
135.9 (d, J = 7.9 Hz), 133.5 (d, J = 2.6 Hz), 130.7 (d, J = 10.3 Hz),
127.5 (d, J = 191 Hz), 126.3 (d, J = 13.7 Hz), 66.5 (d, J = 5.9 Hz),
31.3, 30.4 (d, J = 6.6 Hz), 25.2, 22.5, 14.0; 31P{1H} NMR (162 MHz,
CDCl3) δ 14.7; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C18H3135ClO3P 361.1694, found 361.1692.
Diethyl (6-Chloro-2,3-dihydro-1H-inden-5-yl)phosphonate (4h).
Yellow oil (45 mg, 77%); Rf = 0.24 (petroleum ether/ethyl acetate =
7014
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(376 MHz, CDCl3) δ −57.7; HRMS (ESI-Orbitrap) m/z: [M + H]+
CDCl3) δ 16.2; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C13H1979BrO3P 333.0250, found 333.0247.
calcd for C11H1435ClF3O4P 333.0265, found 333.0262.
Diethyl (2-Bromo-4,5-dimethylphenyl)phosphonate (5g). Yellow
oil (33 mg, 52%); Rf = 0.23 (petroleum ether/ethyl acetate = 4/1 as
the eluent); H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 14.3 Hz,
Diethyl (1-Chloronaphthalen-2-yl)phosphonate (4n). Yellow oil
(39 mg, 65%); Rf = 0.25 (petroleum ether/ethyl acetate = 4/1 as the
eluent); H NMR (400 MHz, CDCl3) δ 8.47−8.43 (m, 1H), 8.03
1
1
1H), 7.44 (d, J = 5.3 Hz, 1H), 4.20−4.06 (m, 4H), 2.27 (s, 3H), 2.24
(s, 3H), 1.35 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 143.3 (d, J = 2.9 Hz), 137.5 (d, J = 8.8 Hz), 135.7 (d, J = 14.1 Hz),
135.2 (d, J = 11.8 Hz), 125.9 (d, J = 193 Hz), 121.8 (d, J = 3.8 Hz),
62.3 (d, J = 5.4 Hz), 19.6, 19.0, 16.3 (d, J = 6.6 Hz); 31P{1H} NMR
(162 MHz, CDCl3) δ 15.7; HRMS (ESI-Orbitrap) m/z: [M + H]+
calcd for C12H1979BrO3P 321.0250, found 321.0247.
(dd, J = 12.3, 8.5 Hz, 1H), 7.89−7.82 (m, 2H), 7.68−7.62 (m, 2H),
4.28−4.14 (m, 4H), 1.37 (t, J = 7.1 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 136.6 (d, J = 2.6 Hz), 136.1 (d, J = 2.3 Hz), 131.1 (d,
J = 11.7 Hz), 129.7 (d, J = 7.8 Hz), 128.7, 128.2, 127.8 (d, J = 1.2
Hz), 126.8 (d, J = 13.6 Hz), 125.4 (d, J = 1.0 Hz), 124.7 (d, J = 190
Hz), 62.6 (d, J = 5.5 Hz), 16.3 (d, J = 6.6 Hz); 31P{1H} NMR (162
MHz, CDCl3) δ 15.1; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd
for C14H1735ClO3P 299.0598, found 299.0594.
Diethyl (2-Bromo-3-methoxyphenyl)phosphonate (5h). Yellow
oil (26 mg, 40%); Rf = 0.30 (petroleum ether/ethyl acetate = 4/1 as
Diethyl (2-Bromophenyl)phosphonate (5a).24 Yellow oil (49 mg,
62%); Rf = 0.23 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.01−7.95 (m, 1H), 7.65−7.61 (m,
1H), 7.39−7.32 (m, 2H), 4.22−4.05 (m, 4H), 1.32 (t, J = 7.1 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 136.2 (d, J = 8.3 Hz),
134.2 (d, J = 11.1 Hz), 133.5 (d, J = 2.7 Hz), 129.4 (d, J = 192 Hz),
126.8 (d, J = 13.6 Hz), 125.1 (d, J = 4.0 Hz), 62.5 (d, J = 5.6 Hz),
16.2 (d, J = 6.6 Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 14.8.
Dimethyl (2-Bromophenyl)phosphonate (5b).4e Yellow oil (29
mg, 55%); Rf = 0.20 (petroleum ether/ethyl acetate = 4/1 as the
1
the eluent); H NMR (400 MHz, CDCl3) δ 7.66−7.60 (m, 1H),
7.39−7.34 (m, 1H), 7.07 (dd, J = 8.3, 1.4 Hz, 1H), 4.24−4.07 (m,
4H), 3.92 (s, 3H), 1.35 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 156.5 (d, J = 15.9 Hz), 131.0 (d, J = 190 Hz), 128.1
(d, J = 3.6 Hz), 128.0 (d, J = 5.2 Hz), 115.7 (d, J = 3.0 Hz), 114.9 (d,
J = 4.6 Hz), 62.6 (d, J = 5.6 Hz), 56.6, 16.3 (d, J = 6.7 Hz); 31P{1H}
NMR (162 MHz, CDCl3) δ 14.8; HRMS (ESI-Orbitrap) m/z: [M +
H]+ calcd for C11H1779BrO4P 323.0042, found 323.0039.
Diethyl (1-Bromonaphthalen-2-yl)phosphonate (5i).26 Yellow oil
(28 mg, 41%); Rf = 0.23 (petroleum ether/ethyl acetate = 4/1 as the
1
eluent); H NMR (400 MHz, CDCl3) δ 8.02−7.96 (m, 1H), 7.71−
1
eluent); H NMR (400 MHz, CDCl3) δ 8.50−8.46 (m, 1H), 8.04
7.65 (m, 1H), 7.43−7.37 (m, 2H), 3.82 (d, J = 11.4 Hz, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 136.4 (d, J = 8.3 Hz), 134.4 (d,
J = 11.3 Hz), 133.8 (d, J = 2.8 Hz), 128.4 (d, J = 194 Hz), 127.0 (d, J
= 13.8 Hz), 125.2 (d, J = 4.0 Hz), 53.0 (d, J = 5.6 Hz); 31P{1H} NMR
(162 MHz, CDCl3) δ 17.8.
(dd, J = 12.2, 8.4 Hz, 1H), 7.91−7.84 (m, 2H), 7.67−7.61 (m, 2H),
4.28−4.14 (m, 4H), 1.38 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 136.0 (d, J = 2.3 Hz), 132.6 (d, J = 12.8 Hz), 130.3
(d, J = 8.1 Hz), 128.7, 128.5, 128.2, 128.1 (d, J = 3.6 Hz), 128.1,
127.6 (d, J = 191 Hz), 127.5 (d, J = 13.5 Hz), 62.6 (d, J = 5.5 Hz),
16.3 (d, J = 6.7 Hz); 31P{1H} NMR (162 MHz, CDCl3) 15.5.
Diethyl (2-Iodophenyl)phosphonate (6a).27 Yellow oil (24 mg,
35%); Rf = 0.22 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.04−7.97 (m, 2H), 7.47−7.41 (m,
1H), 7.19−7.15 (m, 1H), 4.23−4.09 (m, 4H), 1.37 (t, J = 7.1 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.6 (d, J = 12.9 Hz),
136.2 (d, J = 9.0 Hz), 133.3 (d, J = 3.1 Hz), 133.1 (d, J = 192 Hz),
127.5 (d, J = 13.9 Hz), 97.4 (d, J = 5.7 Hz), 62.6 (d, J = 5.6 Hz), 16.3
(d, J = 6.8 Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 14.9.
Diisopropyl (2-Bromophenyl)phosphonate (5c).25 Yellow oil (25
mg, 39%); Rf = 0.28 (petroleum ether/ethyl acetate = 4/1 as the
1
eluent); H NMR (400 MHz, CDCl3) δ 8.05−8.00 (m, 1H), 7.62−
7.59 (m, 1H), 7.37−7.28 (m, 2H), 4.73−4.65 (m, 2H), 1.36 (d, J =
6.2 Hz, 6H), 1.23 (d, J = 6.2 Hz, 6H); 13C{1H} NMR (100 MHz,
CDCl3) δ 136.2 (d, J = 8.4 Hz), 134.2 (d, J = 11.1 Hz), 133.2 (d, J =
2.8 Hz), 130.7 (d, J = 192 Hz), 126.7 (d, J = 13.6 Hz), 125.2 (d, J =
3.7 Hz), 71.4 (d, J = 5.7 Hz), 24.0 (d, J = 4.3 Hz), 23.6 (d, J = 4.8
Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 12.2.
Dibutyl (2-Bromophenyl)phosphonate (5d). Yellow oil (35 mg,
50%); Rf = 0.33 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.05−7.97 (m, 1H), 7.68−7.64 (m,
1H), 7.42−7.33 (m, 2H), 4.16−4.00 (m, 4H), 1.71−1.64 (m, 4H),
1.46−1.37 (m, 4H), 0.90 (t, J = 7.4 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 136.3 (d, J = 8.3 Hz), 134.3 (d, J = 11.1 Hz), 133.5
(d, J = 2.7 Hz), 129.5 (d, J = 193 Hz), 126.9 (d, J = 13.5 Hz), 125.2
(d, J = 4.1 Hz), 66.2 (d, J = 5.9 Hz), 32.4 (d, J = 6.8 Hz), 18.7, 13.6;
31P{1H} NMR (162 MHz, CDCl3) δ 15.0; HRMS (ESI-Orbitrap) m/
z: [M + H]+ calcd for C14H2379BrO3P 349.0563, found 349.0557.
Dihexyl (2-Bromophenyl)phosphonate (5e). Yellow oil (49 mg,
61%); Rf = 0.35 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.04−7.98 (m, 1H), 7.68−7.64 (m,
1H), 7.42−7.34 (m, 2H), 4.15−4.00 (m, 4H), 1.69 (dt, J = 14.6, 6.7
Hz, 4H), 1.41−1.34 (m, 4H), 1.29−1.25 (m, 8H), 0.86 (t, J = 6.9 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 136.3 (d, J = 8.1 Hz),
134.3 (d, J = 11.2 Hz), 133.5 (d, J = 2.7 Hz), 129.5 (d, J = 192 Hz),
126.8 (d, J = 13.6 Hz), 125.2 (d, J = 3.8 Hz), 66.6 (d, J = 5.8 Hz),
31.3, 30.4 (d, J = 6.6 Hz), 25.2, 22.5, 14.0; 31P{1H} NMR (162 MHz,
CDCl3) δ 15.0; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C18H3179BrO3P 405.1189, found 405.1184.
Dimethyl (2-Iodophenyl)phosphonate (6b). Yellow oil (21 mg,
33%); Rf = 0.20 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.06−7.94 (m, 2H), 7.48−7.43 (m,
1H), 7.21−7.17 (m, 1H), 3.81 (d, J = 11.3 Hz, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 141.6 (d, J = 13.0 Hz), 136.3 (d, J = 9.0 Hz),
133.6 (d, J = 3.0 Hz), 132.1 (d, J = 194 Hz), 127.6 (d, J = 13.7 Hz),
97.2 (d, J = 6.0 Hz), 53.0 (d, J = 5.8 Hz); 31P{1H} NMR (162 MHz,
CDCl3) δ 17.9; HRMS (ESI-Orbitrap) m/z: [M + H]+ calcd for
C8H11IO3P 312.9485, found 312.9482.
Diethyl [1,1′-Biphenyl]-2-ylphosphonate (7a).28 Yellow oil (the
Stille coupling: 38 mg, 65%; the Hiyama coupling: 43 mg, 74%; the
Suzuki coupling: 49 mg, 85%); Rf = 0.25 (petroleum ether/ethyl
1
acetate = 4/1 as the eluent); H NMR (400 MHz, CDCl3) δ 8.08−
8.00 (m, 1H), 7.58−7.52 (m, 1H), 7.47−7.30 (m, 7H), 3.98−3.77
(m, 4H), 1.12 (t, J = 7.0 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 146.0 (d, J = 9.8 Hz), 141.3 (d, J = 4.2 Hz), 133.7 (d, J = 9.7 Hz),
131.8 (d, J = 2.9 Hz), 131.2 (d, J = 14.1 Hz), 129.2, 127.4, 127.3,
126.9 (d, J = 187 Hz), 126.7 (d, J = 14.6 Hz), 61.7 (d, J = 6.0 Hz),
16.0 (d, J = 6.8 Hz); 31P{1H} NMR (162 MHz, CDCl3) δ 18.1.
Methyl (E)-3-(2-(Diethoxyphosphoryl)phenyl)acrylate (7b).29
Yellow oil (42 mg, 70%); Rf = 0.21 (petroleum ether/ethyl acetate
= 4/1 as the eluent); 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 15.9
Hz, 1H), 8.06−8.00 (m, 1H), 7.70−7.66 (m, 1H), 7.58−7.54 (m,
1H), 7.48−7.43 (m, 1H), 6.37 (d, J = 15.9 Hz, 1H), 4.25−4.05 (m,
4H), 3.82 (s, 3H), 1.32 (t, J = 7.1 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 166.8, 143.2 (d, J = 4.7 Hz), 137.7 (d, J = 8.8 Hz),
134.4 (d, J = 9.5 Hz), 132.7 (d, J = 2.8 Hz), 129.2 (d, J = 14.7 Hz),
128.0 (d, J = 184 Hz), 127.1 (d, J = 13.3 Hz), 120.7, 62.4 (d, J = 5.7
Hz), 51.8, 16.2 (d, J = 6.2 Hz); 31P{1H} NMR (162 MHz, CDCl3) δ
17.4.
Diethyl (6-Bromo-2,3-dihydro-1H-inden-5-yl)phosphonate (5f).
Yellow oil (35 mg, 53%); Rf = 0.22 (petroleum ether/ethyl acetate =
1
4/1 as the eluent); H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 13.9
Hz, 1H), 7.51 (d, J = 4.7 Hz, 1H), 4.20−4.06 (m, 4H), 2.92 (t, J = 8.4
Hz, 2H), 2.88 (t, J = 7.7 Hz, 2H), 2.14−2.06 (m, 2H), 1.35 (t, J = 7.1
Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.3 (d, J = 2.9 Hz),
143.4 (d, J = 14.3 Hz), 132.2 (d, J = 8.7 Hz), 130.3 (d, J = 12.5 Hz),
126.2 (d, J = 192 Hz), 122.5 (d, J = 4.8 Hz), 62.4 (d, J = 5.4 Hz),
32.8, 32.1, 25.3, 16.3 (d, J = 6.7 Hz); 31P{1H} NMR (162 MHz,
7015
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Diethyl (2-Cyanophenyl)phosphonate (7c).30 Yellow oil (27 mg,
56%); Rf = 0.20 (petroleum ether/ethyl acetate = 4/1 as the eluent);
1H NMR (400 MHz, CDCl3) δ 8.17−8.08 (m, 1H), 7.83−7.80 (m,
1H), 7.73−7.62 (m, 2H), 4.34−4.15 (m, 4H), 1.39 (t, J = 7.1 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 134.6 (d, J = 3.2 Hz),
134.5 (d, J = 16.4 Hz), 132.4 (d, J = 2.7 Hz), 132.3 (d, J = 188 Hz),
132.2 (d, J = 14.1 Hz), 117.1 (d, J = 5.8 Hz), 114.6 (d, J = 4.9 Hz),
63.2 (d, J = 6.0 Hz), 16.2 (d, J = 6.3 Hz); 31P{1H} NMR (162 MHz,
CDCl3) δ 12.6.
in Asymmetric Catalysis: Synthesis and Application; Wiley-VCH:
Weinheim, 2008. (d) Kamer, P. C. J.; van Leeuwen, P. W. N. M.
Phosphorus(III) Ligands in Homogeneous Catalysis: Design and
Synthesis; Wiley-VCH: Chichester, U.K., 2012. (e) McClure, C. K.
Phosphorus in Organic Chemistry; Wiley-VCH: Weinheim, 2012.
(2) Gagnon, K. J.; Perry, H. P.; Clearfield, A. Conventional and
Unconventional Metal−Organic Frameworks Based on Phosphonate
Ligands: MOFs and UMOFs. Chem. Rev. 2012, 112, 1034−1054.
(3) (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. J. Med. Chem. 2002, 45, 919−929. (b) Wydysh, E. A.;
Medghalchi, S. M.; Vadlamudi, A.; Townsend, C. A. Design and
Synthesis of Small Molecule Glycerol 3-Phosphate Acyltransferase
Inhibitors. J. Med. Chem. 2009, 52, 3317−3327. (c) Tsukada, T.;
Takahashi, M.; Takemoto, T.; Kanno, O.; Yamane, T.; Kawamura, S.;
Nishi, T. Synthesis, SAR, and X-ray structure of tricyclic compounds
as potent FBPase inhibitors. Bioorg. Med. Chem. Lett. 2009, 19, 5909−
5912.
(4) (a) Haddad, A. Z.; Kumar, D.; Sampson, K. O.; Matzner, A. M.;
Mashuta, M. S.; Grapperhaus, C. A. Proposed Ligand-Centered
Electrocatalytic Hydrogen Evolution and Hydrogen Oxidation at a
Noninnocent Mononuclear Metal−Thiolate. J. Am. Chem. Soc. 2015,
137, 9238−9241. (b) Daifuku, S. L.; Kneebone, J. L.; Snyder, B. E. R.;
Neidig, M. L. Iron(II) Active Species in Iron−Bisphosphine Catalyzed
Kumada and Suzuki−Miyaura Cross-Couplings of Phenyl Nucleo-
philes and Secondary Alkyl Halides. J. Am. Chem. Soc. 2015, 137,
11432−11444. (c) Zhang, J.; Ding, D.; Wei, Y.; Xu, H. Extremely
condensing triplet states of DPEPO-type hosts through constitutional
isomerization for high-efficiency deep-blue thermally activated
delayed fluorescence diodes. Chem. Sci. 2016, 7, 2870−2882.
(d) Han, C.; Zhang, Z.; Ding, D.; Xu, H. Dipole-Dipole Interaction
Management for Efficient Blue Thermally Activated Delayed
Fluorescence Diodes. Chem. 2018, 4, 2154−2167. (e) Xu, F.; Duke,
O. M.; Rojas, D.; Eichelberger, H. M.; Kim, R. S.; Clark, T. B.;
Watson, D. A. Arylphosphonate-Directed Ortho C−H Borylation:
Rapid Entry into Highly-Substituted Phosphoarenes. J. Am. Chem. Soc.
2020, 142, 11988−11992.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00550.
1
Copies of H, 13C{1H} and 31P{1H} NMR spectra for
compounds 4, 5, 6, and 7 (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Qian Chen − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, P. R. China; orcid.org/0000-0002-0818-6028;
Email: qianchen@gdut.edu.cn
Authors
Yuanting Huang − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, P. R. China
Yifan Hu − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, P. R. China
Yukun Han − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, P. R. China
Yingcong Ou − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, P. R. China
(5) (a) Martin, R.; Buchwald, S. L. Palladium-Catalyzed Suzuki−
Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phos-
phine Ligands. Acc. Chem. Res. 2008, 41, 1461−1473. (b) Surry, D. S.;
Buchwald, S. L. Biaryl Phosphane Ligands in Palladium-Catalyzed
Amination. Angew. Chem., Int. Ed. 2008, 47, 6338−6361. (c) Surry, D.
S.; Buchwald, S. L. Dialkylbiaryl phosphines in Pd-catalyzed
amination: a user’s guide. Chem. Sci. 2011, 2, 27−50.
Yanping Huo − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, P. R. China
Xianwei Li − School of Chemical Engineering and Light
Industry, Guangdong University of Technology, Guangzhou
510006, P. R. China; orcid.org/0000-0002-4014-6712
(6) (a) Imamoto, T.; Tamura, K.; Zhang, Z.; Horiuchi, Y.; Sugiya,
M.; Yoshida, K.; Yanagisawa, A.; Gridnev, I. D. Rigid P-Chiral
Phosphine Ligands with tert-Butylmethylphosphino Groups for
Rhodium-Catalyzed Asymmetric Hydrogenation of Functionalized
Alkenes. J. Am. Chem. Soc. 2012, 134, 1754−1769. (b) Ota, Y.; Ito, S.;
Kuroda, J.-I.; Okumura, Y.; Nozaki, K. Quantification of the Steric
Influence of Alkylphosphine−Sulfonate Ligands on Polymerization,
Leading to High-Molecular-Weight Copolymers of Ethylene and
Polar Monomers. J. Am. Chem. Soc. 2014, 136, 11898−11901.
(7) (a) Jablonkai, E.; Keglevich, G. P-C Bond Formation by
Coupling Reactions Utilizing > P(O)H Species as the Reagents. Curr.
Org. Synth. 2014, 11, 429−453. (b) Jablonkai, E.; Keglevich, G.
Advances and New Variations of the Hirao Reaction. Org. Prep.
Proced. Int. 2014, 46, 281−316.
(8) For selected examples of transition-metal-catalyzed C−H
activation of arylphosphorus compounds, see: (a) Nguyen, T. T.;
Grigorjeva, L.; Daugulis, O. Cobalt-Catalyzed, Aminoquinoline-
Directed Functionalization of Phosphinic Amide sp2 C−H Bonds.
ACS Catal. 2016, 6, 551−554. (b) Unoh, Y.; Yokoyama, Y.; Satoh, T.;
Hirano, K.; Miura, M. Regioselective Synthesis of Benzo[b]phosphole
Derivatives via Direct ortho-Alkenylation and Cyclization of
Arylthiophosphinamides. Org. Lett. 2016, 18, 5436−5439. (c) Liu,
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00550
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the 100 Young Talents Programme of Guangdong
University of Technology (No. 220413506), the Science and
Technology Planning Project of Guangdong Province (Nos.
2017A010103044 and 2019A050510042), and the National
Undergraduate Training Program for Innovation and En-
trepreneurship (No. D202011292349499886) for financial
support.
REFERENCES
■
(1) (a) Tang, W.; Zhang, X. New Chiral Phosphorus Ligands for
Enantioselective Hydrogenation. Chem. Rev. 2003, 103, 3029−3070.
(b) Grushin, V. V. Mixed Phosphine−Phosphine Oxide Ligands.
Chem. Rev. 2004, 104, 1629−1662. (c) Börner, A. Phosphorus Ligands
7016
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Z.; Wu, J.-Q.; Yang, S.-D. Ir(III)-Catalyzed Direct C−H Function-
alization of Arylphosphine Oxides: A Strategy for MOP-Type Ligands
Synthesis. Org. Lett. 2017, 19, 5434−5437. (d) Fukuda, K.; Iwasawa,
N.; Takaya, J. Ruthenium-Catalyzed ortho C−H Borylation of
Arylphosphines. Angew. Chem., Int. Ed. 2019, 58, 2850−2853.
(e) Sun, S.-Z.; Shang, M.; Xu, H.; Cheng, T.-J.; Li, M.-H.; Dai, H.-
X. Copper mediated C(sp2)−H amination and hydroxylation of
phosphinamides. Chem. Commun. 2020, 56, 1444−1447.
(9) For recent reviews, see: (a) Bhojgude, S. S.; Bhunia, A.; Biju, A.
T. Employing Arynes in Diels−Alder Reactions and Transition-Metal-
Free Multicomponent Coupling and Arylation Reactions. Acc. Chem.
Res. 2016, 49, 1658−1670. (b) Shi, J.; Li, Y.; Li, Y. Aryne
multifunctionalization with benzdiyne and benztriyne equivalents.
Chem. Soc. Rev. 2017, 46, 1707−1719. (c) Takikawa, H.; Nishii, A.;
Sakai, T.; Suzuki, K. Aryne-based strategy in the total synthesis of
naturally occurring polycyclic compounds. Chem. Soc. Rev. 2018, 47,
8030−8056. (d) He, J.; Qiu, D.; Li, Y. Strategies toward Aryne
Multifunctionalization via 1,2-Benzdiyne and Benzyne. Acc. Chem. Res.
2020, 53, 508−519. (e) Werz, D. B.; Biju, A. T. Uncovering the
Neglected Similarities of Arynes and Donor−Acceptor Cyclo-
propanes. Angew. Chem., Int. Ed. 2020, 59, 3385−3398. (f) Ghorai,
S.; Lee, D. Aryne-Based Multicomponent Coupling Reactions. Synlett
2020, 31, 750.
(10) For recent examples, see: (a) Xu, H.; He, J.; Shi, J.; Tan, L.;
Qiu, D.; Luo, X.; Li, Y. Domino Aryne Annulation via a
Nucleophilic−Ene Process. J. Am. Chem. Soc. 2018, 140, 3555−
3559. (b) Zuo, Z.; Wang, H.; Diao, Y.; Ge, Y.; Liu, J.; Luan, X.
Palladium-Catalyzed Aryne Insertion/Arene Dearomatization Domi-
no Reaction: A Highly Chemoselective Route to Spirofluorenes. ACS
Catal. 2018, 8, 11029−11034. (c) Mesgar, M.; Nguyen-Le, J.;
Daugulis, O. New Hindered Amide Base for Aryne Insertion into Si−
P, Si−S, Si−N, and C−C Bonds. J. Am. Chem. Soc. 2018, 140, 13703−
13710. (d) Xiao, X.; Hoye, T. R. One-Pot, Three-Aryne Cascade
Strategy for Naphthalene Formation from 1,3-Diynes and 1,2-
Benzdiyne Equivalents. J. Am. Chem. Soc. 2019, 141, 9813−9818.
(e) Matsuzawa, T.; Hosoya, T.; Yoshida, S. One-step synthesis of
benzo[b]thiophenes by aryne reaction with alkynyl sulfides. Chem. Sci.
2020, 11, 9691−9696.
(11) For recent reviews, see: (a) Huang, Y.; Chen, Q. Recent
Progress in P- and S-Arylation Reactions of Arynes. Youji Huaxue
2020, 40, 4087−4100 (in Chinese). (b) Neog, K.; Gogoi, P. Recent
advances in the synthesis of organophosphorus compounds via
Kobayashi’s aryne precursor: a review. Org. Biomol. Chem. 2020, 18,
9549−9561. (c) Chen, J.; Fan, R.; Liu, Z.; Tan, J. Reactions of
Organophosphorus Compounds with Arynes: Reactivity and Mech-
anism. Adv. Synth. Catal. 2021, 363, 657−667.
(d) Xie, P.; Yang, S.; Guo, Y.; Cai, Z.; Dai, B.; He, L. Multicomponent
Reaction of Phosphines, Benzynes, and CO2: Facile Synthesis of
Stable Zwitterionic Phosphonium Inner Salts. J. Org. Chem. 2020, 85,
8872−8880.
̈
(14) (a) Wittig, G.; Benz, E. Uber das Verhalten von Dehydrobenzol
gegenu
̈
ber nucleophilen und elektrophilen Reagenzien. Chem. Ber.
1959, 92, 1999−2013. (b) Wittig, G.; Matzura, H. Quaternierung von
Triarylphosphinen mit Dehydroaromaten. Liebigs Ann. Chem. 1970,
732, 97−106. (c) Wittig, G.; Braun, H. Optisch aktive, vierfach
ungleich ligierte Tetraarylphosphonium-Salze. Liebigs Ann. Chem.
1971, 751, 27−31.
(15) (a) Chen, Q.; Yan, X.; Du, Z.; Zhang, K.; Wen, C. P-Arylation
of Dialkyl Phosphites and Secondary Phosphine Oxides with Arynes.
J. Org. Chem. 2016, 81, 276−281. (b) Chen, Q.; Yan, X.; Wen, C.;
Zeng, J.; Huang, Y.; Liu, X.; Zhang, K. Copper-Catalyzed Addition of
H−P(O) Bonds to Arynes. J. Org. Chem. 2016, 81, 9476−9482.
(c) Chen, Q.; Zeng, J.; Yan, X.; Huang, Y.; Wen, C.; Liu, X.; Zhang,
K. Electrophilic Fluorination of Secondary Phosphine Oxides and Its
Application to P−O Bond Construction. J. Org. Chem. 2016, 81,
10043−10048. (d) Chen, Q.; Wen, C.; Wang, X.; Yu, G.; Ou, Y.;
Huo, Y.; Zhang, K. DDQ-Promoted Allylic C−H Phosphorylation of
1,3-Diarylpropenes. Adv. Synth. Catal. 2018, 360, 3590−3594.
(e) Chen, Q.; Wang, X.; Yu, G.; Wen, C.; Huo, Y. DDQ-mediated
direct C(sp3)−H phosphorylation of xanthene derivatives. Org. Chem.
Front. 2018, 5, 2652−2656. (f) Wang, X.; Ou, Y.; Peng, Z.; Yu, G.;
Huang, Y.; Li, X.; Huo, Y.; Chen, Q. TBHP/NH4I-Mediated Direct
N−H Phosphorylation of Imines and Imidates. J. Org. Chem. 2019,
84, 14949−14956. (g) Ou, Y.; Huang, Y.; He, Z.; Yu, G.; Huo, Y.; Li,
X.; Gao, Y.; Chen, Q. A phosphoryl radical-initiated Atherton−Todd-
type reaction under open air. Chem. Commun. 2020, 56, 1357−1360.
(h) Ou, Y.; Huang, Y.; Liu, Y.; Huo, Y.; Gao, Y.; Li, X.; Chen, Q.
Iron-Catalyzed and Air-Mediated C(sp3)−H Phosphorylation of 1,3-
Dicarbonyl Compounds Involving C−C Bond Cleavage. Adv. Synth.
Catal. 2020, 362, 5783−5787.
(16) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Fluoride-Induced
1,2-Elimination of o-Trimethylsilylphenyl Triflate to Benzyne Under
Mild Conditions. Chem. Lett. 1983, 12, 1211−1214.
(17) Dhokale, R. A.; Mhaske, S. B. P-Arylation: Arynes to Aryl-
Phosphonates, -Phosphinates, and -Phosphine Oxides. Org. Lett.
2013, 15, 2218−2221.
(18) Liu, Z.; Larock, R. C. Facile O-Arylation of Phenols and
Carboxylic Acids. Org. Lett. 2004, 6, 99−102.
(19) (a) Arbusow, B. A. Michaelis-Arbusow-und Perkow-Reaktio-
nen. Pure Appl. Chem. 1964, 9, 307−336. (b) Bhattacharya, A. K.;
Thyagarajan, G. The Michaelis−Arbuzov Rearrangement. Chem. Rev.
1981, 81, 415−430.
(12) For recent examples, see: (a) Yoshida, H.; Asatsu, Y.; Mimura,
Y.; Ito, Y.; Ohshita, J.; Takaki, K. Three-Component Coupling of
Arynes and Organic Bromides. Angew. Chem., Int. Ed. 2011, 50,
9676−9679. (b) Ross, S. P.; Hoye, T. R. Multiheterocyclic Motifs via
Three-Component Reactions of Benzynes, Cyclic Amines, and Protic
Nucleophiles. Org. Lett. 2018, 20, 100−103. (c) Zheng, T.; Tan, J.;
Fan, R.; Su, S.; Liu, B.; Tan, C.; Xu, K. Diverse ring opening of
thietanes and other cyclic sulfides: an electrophilic aryne activation
approach. Chem. Commun. 2018, 54, 1303−1306. (d) Gaykar, R. N.;
Guin, A.; Bhattacharjee, S.; Biju, A. T. Three-Component Amino-
selenation of Arynes. Org. Lett. 2019, 21, 9613−9617. (e) Li, S.-J.;
Han, L.; Tian, S.-K. 1,2-Aminohalogenation of arynes with amines and
organohalides. Chem. Commun. 2019, 55, 11255−11258.
(13) (a) Bhunia, A.; Kaicharla, T.; Porwal, D.; Gonnade, R. G.; Biju,
A. T. Multicomponent reactions involving phosphines, arynes and
aldehydes. Chem. Commun. 2014, 50, 11389−11392. (b) Bhunia, A.;
Roy, T.; Gonnade, R. G.; Biju, A. T. Rapid Access to Benzoxaphosp-
holes and Their Spiro Analogues by a Three-Component Coupling
Involving Arynes, Phosphines, and Activated Ketones. Org. Lett. 2014,
16, 5132−5135. (c) Bhattacharjee, S.; Raju, A.; Gaykar, R. N.;
Gonnade, R. G.; Roy, T.; Biju, A. T. Rapid Synthesis of Zwitterionic
Phosphonium Benzoates by a Three-Component Coupling Involving
Phosphines, Arynes and CO2. Chem. - Asian J. 2020, 15, 2203−2207.
(20) Xu, W.; Hu, G.; Xu, P.; Gao, Y.; Yin, Y.; Zhao, Y. Palladium-
Catalyzed C−P Cross-Coupling of Arylhydrazines with H-Phospho-
nates via C−N Bond Cleavage. Adv. Synth. Catal. 2014, 356, 2948−
2954.
(21) Ishikawa, S.; Manabe, K. Synthesis of hydroxylated oligoarene-
type phosphines by a repetitive two-step method. Tetrahedron 2010,
66, 297−303.
(22) Xu, K.; Yang, F.; Zhang, G.; Wu, Y. Palladacycle-catalyzed
phosphonation of aryl halides in neat water. Green Chem. 2013, 15,
1055−1060.
(23) Lu, X.; Zhu, J. Palladium-catalyzed reaction of aryl
polyfluoroalkanesulfonates with O, O-dialkyl phosphonates. Synthesis
1987, 1987, 726−727.
(24) Bonnaventure, I.; Charette, A. B. Probing the Importance of the
Hemilabile Site of Bis(phosphine) Monoxide Ligands in the Copper-
Catalyzed Addition of Diethylzinc to N-Phosphinoylimines: Discov-
ery of New Effective Chiral Ligands. J. Org. Chem. 2008, 73, 6330−
6340.
(25) Wilders, A. M.; Contrella, N. D.; Sampson, J. R.; Zheng, M.;
Jordan, R. F. Allosteric Effects in Ethylene Polymerization Catalysis.
Enhancement of Performance of Phosphine-Phosphinate and
Phosphine-Phosphonate Palladium Alkyl Catalysts by Remote
Binding of B(C6F5)3. Organometallics 2017, 36, 4990−5002.
7017
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
(26) Feng, J.; Li, B.; He, Y.; Gu, Z. Enantioselective Synthesis of
Atropisomeric Vinyl Arene Compounds by Palladium Catalysis: A
Carbene Strategy. Angew. Chem., Int. Ed. 2016, 55, 2186−2190.
(27) Kawahata, N. H.; Yang, M. H.; Luke, G. P.; Shakespeare, W. C.;
Sundaramoorthi, R.; Wang, Y.; Johnson, D.; Merry, T.; Violette, S.;
Guan, W.; Bartlett, C.; Smith, J.; Hatada, M.; Lu, X.; Dalgarno, D. C.;
Eyermann, C. J.; Bohacek, R. S.; Sawyer, T. K. A novel
phosphotyrosine mimetic 4′-carboxymethyloxy-3′-phosphonopheny-
lalanine (cpp): exploitation in the design of nonpeptide inhibitors of
pp60Src SH2 domain. Bioorg. Med. Chem. Lett. 2001, 11, 2319−2323.
(28) (a) Kendall, A. J.; Salazar, C. A.; Martino, P. F.; Tyler, D. R.
Direct Conversion of Phosphonates to Phosphine Oxides: An
Improved Synthetic Route to Phosphines Including the First
Synthesis of Methyl JohnPhos. Organometallics 2014, 33, 6171−
6178. (b) Zhang, L.; Zhang, Z.; Zhang, J.; Li, K.; Mo, F. Oxidant-free
oxidation of C−H bonds by cathodic hydrogen evolution: a
phosphonic Kolbe oxidation/cyclization process. Green Chem. 2018,
20, 3916−3920.
(29) Peng, A.-Y.; Chen, B.-T.; Wang, Z.; Wang, B.; Mo, X.-B.; Wang,
Y.-Y.; Chen, P.-J. Pd(0)/iodide salt-mediated Heck reaction of aryl
nonaflates: Application to the synthesis of 2-(1-alkenyl)-
phenylphosphonates. J. Fluorine Chem. 2011, 132, 982−986.
(30) (a) Shaikh, R. S.; Dusel, S. J. S.; König, B. Visible-Light Photo-
̈
Arbuzov Reaction of Aryl Bromides and Trialkyl Phosphites Yielding
Aryl Phosphonates. ACS Catal. 2016, 6, 8410−8414. (b) Ghosh, I.;
Shaikh, R. S.; König, B. Sensitization-Initiated Electron Transfer for
Photoredox Catalysis. Angew. Chem., Int. Ed. 2017, 56, 8544−8549.
7018
https://doi.org/10.1021/acs.joc.1c00550
J. Org. Chem. 2021, 86, 7010−7018