Electrochemical Dehydrogenative Phosphorylation of Alcohols for the Synthesis of Organophosphinates

Article abstract of DOI:10.1021/acs.joc.8b02882

An eco-friendly and efficient method for the synthesis of organophosphinates via an electrochemical cross-dehydrogenative-coupling reaction between alcohols and secondary phosphine oxides has been developed. This electrochemical reaction was conducted at

Full text of DOI:10.1021/acs.joc.8b02882

Article
pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Electrochemical Dehydrogenative Phosphorylation of Alcohols for
the Synthesis of Organophosphinates
Lingling Deng,† Yang Wang,† Haibo Mei,‡ Yi Pan,† and Jianlin Han*,†,‡
†School of Chemistry and Chemical Engineering, State Key laboratory of Coordination Chemistry, Jiangsu Key Laboratory of
Advanced Organic Materials, Nanjing University, Nanjing 210093, China
‡College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, Jiangsu, China
S
* Supporting Information
ABSTRACT: An eco-friendly and efficient method for the
synthesis of organophosphinates via an electrochemical cross-
dehydrogenative-coupling reaction between alcohols and secondary
phosphine oxides has been developed. This electrochemical
reaction was conducted at room temperature without the addition
of any oxidant, metal catalyst, or additive, which provides a new
strategy for the synthesis of organophosphinates.
Scheme 1. Synthesis of Organophosphinates
INTRODUCTION
■
The organophosphinates belong to an extremely important
type of organic compounds in organic, biological, and
medicinal chemistries, which have been demonstrated to
show high bioactivity. This structural unit is also found to exist
in many natural products.1 Furthermore, they have been
developed as efficient chiral phosphorus ligands in many
asymmetric catalytic reactions.2 Thus, development of a
synthetic method for the preparation of organophosphinates
has become a compelling interest and attracted wide research
attention. The traditional method for the preparation of these
compounds is the direct esterification of alcohols, which relies
on the use of toxic and moisture-sensitive phosphoryl
halides.3,4 In the past few years, direct cross-dehydrogenative
coupling (CDC) reactions between hydrogen phosphoryl
compounds and alcohols have been developed for the synthesis
of these compounds.5 In 2016, the Chen and Han group
reported a synthetic method for the preparation of phosphoryl
compounds via a Fe(acac)2/1,10-phen-catalyzed CDC reaction
of P(O)−H compounds with alcohols at high temperature
(Scheme 1a).6 In 2017, the Li group developed a Cu-catalyzed
oxidative CDC reaction of H-phosphonates with carboxylic
acids at 70 °C with 4 equiv of dicumyl peroxide as the oxidant
(Scheme 1b).7 Although the metal-free methods for the
preparation of phosphoryl compounds via CDC reaction have
also been developed, an additional oxidant, such as SelectFluor
or H2O2, is needed for the transformation (Scheme 1c,d).8
Electrochemical synthesis is a very special type of organic
transformation and has emerged as an active research area in
the past few years.9 Different from the traditional oxidative
reaction, electrosynthesis is regarded as a green transformation,
as it does not require the use of chemical oxidant. Several types
of electroorganic oxidative transformations, such as dehydro-
genation cross-coupling reactions,10 functionalization of
unsaturated C−C bonds,11 cascade cyclization,12 and other
reactions,13 have been developed, which achieved the C−X (X
= C, O, N, S), N−S, N−N, N−P, and S−S bond
formations.10−13
Inspired by recent developments in the area of synthetic
electrochemistry9−13 and challenged by the problems in the
previous systems,6−8 we herein report the first example of
electrochemical cross-dehydrogenative coupling of alcohols
with phosphine oxides for the P(O)−O bond formation
(Scheme 1e). Notably, Torii and co-workers reported a related
work on the electrochemical cross-dehydrogenative coupling of
dialkyl phosphites with amines for the P−N bond formation.14
To the best of our knowledge, the construction of the P−O
bond via the electrochemical method has never been reported.
Received: November 11, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.8b02882
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
This electrochemical reaction was conducted at room
temperature without the use of any oxidant and metal catalyst,
which provides a new strategy for the synthesis of organo-
phosphinates.
reaction yield was found, which indicated 3.0 V voltage was the
best reaction condition. Finally, the addition of additives into
the system was demonstrated to be unsuccessful, and almost
the same level of chemical yield was obtained (entries 19−20).
After obtaining the optimized reaction conditions, we then
investigated the substrate generality of this electrochemical
coupling reaction (Scheme 2). The reaction tolerated a wide
RESULTS AND DISCUSSION
■
Initially, diphenylphosphine oxide 1a and methanol 2a were
selected as the model compounds for the electrochemical CDC
reaction, and the results are summarized in Table 1. The
Scheme 2. Substrate Scope Study of P(O)−H
a,b
Compounds
a
Table 1. Optimization of the Reaction Conditions
b
entry anode/cathode
solvent
electrolyte voltage (V) yield (%)
1
2
3
4
5
6
7
8
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
Pt/Pt
C/Ni
C/C
C/Cu
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
C/Pt
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCM
NH4I
3
3
3
3
3
3
3
3
3
3
3
3
1
1.5
2
2.5
3.5
4
40
nr
LiClO4
Bu4NBr
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
Bu4NI
84
86
56
55
88
50
92
86
76
11
6
12
75
82
84
80
78
84
c
9
10
11
12
13
14
15
16
17
18
19
20
DMF
dioxane
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
a
Reaction conditions: graphite anode (1 cm × 1 cm × 0.3 cm), Pt
cathode (1 cm × 1 cm × 0.2 mm), at 3.0 V cell potential, 1 (0.2
mmol), 2a (1 mL), MeCN (4 mL), Bu4NI (2 equiv) under air at
b
room temperature for 12 h. Isolated yield based on 1.
d
e
3
3
range of diarylphosphine oxides bearing electron-donating and
-withdrawing groups at different positions on the phenyl ring
and proceeded smoothly to give the corresponding organo-
phosphinates 3a−l in good to excellent yields (59−92%). For
example, a series of methyl-substituted derivatives 1b−d
reacted with methanol 2a well, and the chemical yields ranged
from 59 to 84%. Notably, the substrate-bearing dimethyl-
substituted phenyl 1e could also work well in this system,
affording the desired product 3e in 73% yield. The electronic
properties of the substituent had almost no noticeable effect on
the reaction efficiency. For example, the substrates with a para-
substituted phenyl group, 2d, 2f−i, either with a strong
electron-withdrawing group (1f,g) or with an electron-
donating group (1i) could be well tolerated in the reaction
resulting in good yields (76−83% yields, 3f−i). Taking into
account the great value of alkyl phosphinates, we were curious
to develop the alkyl phosphine oxides as the substrates for this
reaction. We were pleased that the alkyl phosphine oxides,
such as dibenzylphosphine oxide 1j, dicyclohexylphosphine
oxide 1k, and dicyclopentylphosphine oxide 1l, were also
suitable substrates for this reaction, resulting in the desired
products in 60−82% yields (3j−l). Dibutyl phosphonate 1m
could participate in this reaction, and the desired product was
isolated in 30% yield (3m).
a
Reaction conditions: 1a (0.2 mmol), 2a (1 mL), solvent (4 mL),
electrolyte (2.0 equiv) in an undivided cell at room temperature for
b
c
d
12 h. Isolated yield based on 1a. Argon atmosphere. K2CO3 (2.0
equiv) was added. Et3N (2.0 equiv) was added.
e
reaction occurred when it was carried out in acetonitrile by the
use of platinum-plate anode and cathode with H4NI as an
electrolyte, at 3.0 V cell potential at room temperature under
air for 12 h, affording the corresponding coupling product 3a
in 40% isolated yield (entry 1). Other electrolytes, such as
LiClO4, were tried but did not work for this reaction (entry 2).
The reaction proceeded smoothly with Bu4NBr (entry 3) or
Bu4NI (entry 4) as electrolyte, and the desired product 3a was
obtained in dramatically increased yields (84% and 86%,
respectively). Performing the reaction under an argon
atmosphere did not provide any improvement of the chemical
yield (56%, entry 5). To further improve the yield, several
types of electrodes, such as nickel, graphite and copper plates,
were scanned for this reaction (entries 6−9). The best result
was obtained when the graphite electrode was used for the
anode and the platinum plate was used for the cathode (92%
yield, entry 9). Solvent showed a great effect on this reaction.
The use of dichloromethane, DMF, and 1,4-dioxane (entries
10−12) also afforded the desired product but in lower
chemical yields. Variation of the voltage from 1.0 to 4.0 V
was carried out (entries 13−18), and no improvement on the
Then another part of the substrate scope study with regard
to the alcohols was carried out, and the results are shown in
Scheme 3. Almost all of the examined linear alcohols were
B
DOI: 10.1021/acs.joc.8b02882
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Article
a,b
Scheme 3. Substrate Scope Study of Alcohols
Scheme 4. Large-Scale Synthesis
an efficient and eco-friendly way for the synthesis of
organophosphinates.
The final goal of this study was the mechanism investigation
(Scheme 5). The reaction also proceeded smoothly when a
Scheme 5. Control Experiments
a
Reaction conditions: graphite anode (1 cm × 1 cm × 0.3 cm), Pt
cathode (1 cm × 1 cm × 0.2 mm), at 3.0 V cell potential, 1 (0.2
mmol), 2 (120 equiv), MeCN (4 mL), Bu4NI (2 equiv) under air at
b
room temperature for 12 h. Isolated yield based on 1.
radical inhibitor TEMPO (3.0 equiv) was added to the system
under the standard reaction conditions, and the desired
product 3a was obtained in 80% yield. A similar result was also
found when a radical trapping reagent 1,1-diphenylethylene
was added into the reaction under standard conditions, and the
desired coupling product 3a was isolated in 75% yield. These
results clearly disclose that this is not a radical process.
On the basis of the above results and the previous reports,8b
a possible mechanism has been provided in Scheme 6 for this
suitable substrates and reacted very well with diphenylphos-
phine oxide 1a, affording the corresponding products in
moderate to good chemical yields (36−78%). It should be
mentioned that the isolated yields for the primary alcohols
became lower when the length of alkyl chain increased (4a, 4c,
4e and 4h). A moderate yield (55%, 4h) was obtained when
pentan-1-ol was used as a coupling partner. An obvious steric
effect of this reaction was observed when secondary and
tertiary alcohols were used as substrates. For example, the
reaction of 2-propanol also proceeded, giving the desired
product with only 36% yield (4d). Unfortunately, the reaction
with the tertiary alcohol did not happen at all (4g). Then, three
cyclic alcohols were investigated in this electrochemical
system, and a similar trend was also found from these
reactions. It was obvious that the alcohols bearing larger alkyl
membered ring gave lower chemical yields (4i−k). Two
fluorinated alcohols, 2,2,2-trifluoroethanol and 1,1,1,3,3,3-
hexafluoropropan-2-ol, were also examined in this reaction.
These two fluorinated substrates worked very well in the
coupling reactions, yielding the products 4l,m in moderate
yields. Finally, we tried to use water as a coupling partner in
this electrochemical coupling reaction with diphenylphosphine
oxide. However, the reaction was unsuccessful and failed to
give the desired product after 12 h (4n).
Scheme 6. Possible Mechanism
electrochemical transformation. Initially, iodide anion is
oxidized at the anode to generate iodide.15 Then, electrophilic
iodination of H-phosphite 1 provides the phosphoryl iodide
intermediate A. Subsequently, the nucleophilic substitution
happens between intermediate A and alcohol 2, affording the
final coupling product 3, iodine anion for the next cycle, and
proton. At the same time, the proton is reduced to release
hydrogen gas at the cathode.
As another synthetic objective of this study, we tried to
demonstrate the possibility of the large-scale synthesis of this
electrochemical reaction (Scheme 4). The reaction was
conducted with the use of 5 mmol of diphenylphosphine
oxide 1a and methanol. The reaction proceeded smoothly, and
the desired product 3a was obtained in 88% isolated yield after
the reaction time was prolonged to 24 h (Scheme 4a). Also,
87% yield was obtained when the reaction was conducted in 25
mL of acetonitrile (Scheme 4b). This result clearly indicates
the high potential of this electrochemical coupling reaction as
C
DOI: 10.1021/acs.joc.8b02882
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mL of MeCN and 25 mL of CH3OH were added into bottle by
syringe. The reaction mixture was stirred and electrolyzed at a
constant voltage of 3 V (the dual display potentiostat was
operating in constant voltage mode) under room temperature
for 24 h. When the reaction was finished, the solution was
removed with a rotary evaporator. The pure product 3a was
obtained in 88% yield (1.02 g) by flash column chromatog-
raphy on silica gel (petroleum ether/ethyl acetate = 3:1).
Control Experiment with the Addition of TEMPO. The
reaction took place in an oven-dried undivided three-necked
bottle (10 mL) equipped with a stir bar and Bu4NI (0.4
mmol). The bottle was equipped with carbon electrodes (10×
10× 3 mm) as the anode and platinum electrodes (10× 10×
0.2 mm) as the cathode under air. H-Phosphine oxides (0.2
mmol) and TEMPO (3 equiv) were added into bottle. Then 4
mL of MeCN and 1 mL of CH3OH were added into the bottle
by syringe. The reaction mixture was stirred and electrolyzed at
a constant voltage of 3 V (the dual display potentiostat was
operating in constant voltage mode) under room temperature
for 12 h. When the reaction was finished, the solution was
removed with a rotary evaporator. The pure product 3a was
obtained by flash column chromatography on silica gel
(petroleum ether/ethyl acetate = 3:1).
Control Experiment with the Addition of 1,1-
Diphenylethylene. The reaction took place in an oven-
dried undivided three-necked bottle (10 mL) equipped with a
stir bar and Bu4NI (0.4 mmol). The bottle was equipped with
carbon electrodes (10× 10× 3 mm) as the anode and platinum
electrodes (10× 10× 0.2 mm) as the cathode under air. H-
Phosphine oxides (0.2 mmol) were added into the bottle.
Then 4 mL of MeCN, 1 mL of CH3OH, and 1,1-
diphenylethylene (3 equiv) were added into the bottle by
syringe. The reaction mixture was stirred and electrolyzed at a
constant voltage of 3 V (the dual display potentiostat was
operating in constant voltage mode) under room temperature
for 12 h. When the reaction was finished, the solution was
removed with a rotary evaporator. The pure product 3a was
obtained by flash column chromatography on silica gel
(petroleum ether/ethyl acetate = 3:1).
General Procedure for the Electrochemical CDC
Reaction. The reaction took place in an oven-dried undivided
three-necked bottle (10 mL) equipped with a stir bar and
Bu4NI (0.4 mmol). The bottle was equipped with carbon
electrodes (10 × 10 × 3 mm) as the anode and platinum
electrodes (10 × 10 × 0.2 mm) as the cathode under air. H-
Phosphine oxides 1 (0.2 mmol) was added into bottle. Then
MeCN (4 mL) and alcohols 2 (120 equiv) were added into the
bottle by syringe. The reaction mixture was stirred and
electrolyzed at a constant voltage of 3 V (the dual display
potentiostat was operating in constant voltage mode) under
room temperature for 12 h. When the reaction was finished,
the solution was removed on a rotary evaporator. The pure
product 3 or 4 was obtained by flash column chromatography
on silica gel (petroleum ether/ethyl acetate = 3:1).
Methyl diphenylphosphinate (3a): colorless oil, 43 mg
(92% yield); 1H NMR (400 MHz, chloroform-d) δ 7.86−7.78
(m, 4H), 7.56−7.42 (m, 6H), 3.76 (d, J = 11.2 Hz, 3H); 13C
NMR {1H} (101 MHz, chloroform-d) δ 132.2 (d, J = 2.8 Hz),
131.7 (d, J = 10.1 Hz), 131.0 (d, J = 137.8 Hz), 128.6 (d, J =
13.1 Hz), 51.6 (d, J = 6.0 Hz); 31P NMR (162 MHz,
chloroform-d) δ 33.28; HRMS (TOF MS ESI) calcd for
C13H14O2P+ [M + H]+ 233.0726, found 233.0728; IR (cm−1)
CONCLUSION
■
In summary, an electrochemical cross-dehydrogenative-cou-
pling reaction between alcohols and secondary phosphine
oxides has been reported. Using this eco-friendly method, we
were able to synthesize the organophosphinates from readily
available starting materials under oxidant-free conditions. This
work represents the first example on the P−O bond formation
under electrochemical conditions, also provides a new and
green access to organophosphinates.
EXPERIMENTAL SECTION
■
General Procedures for the Synthesis of Phosphine
Oxides 1. All of the phosphine oxides are known compounds,
and the commercially unavailable phosphine oxides were
prepared according to the previous reports.16 Aryl bromide
(16.5 mmol, 3.3 equiv) in THF (10 mL) was added slowly to a
suspension of magnesium turnings (600 mg, 25 mmol, 5.0
equiv) in THF (15 mL) containing a catalytic amount of I2
(cat.) and refluxed for 1 h. A solution of diethyl phosphate
(690 mg, 5.0 mmol, 1.0 equiv) in THF (5 mL) was added
slowly at 0 °C. Then the mixture was warmed to room
temperature and stirred over 3 h. After ammonium chloride
solution quenching, the precipitated solid was removed by
filtration. The filtrate was extracted with ethyl acetate, washed
with sodium chloride solution, and dried over Na2SO4. After
filtration and concentration, the pure product was obtained by
flash column chromatography on silica gel (petroleum ether/
ethyl acetate = 1:1).
Di-o-tolylphosphine oxide (1b):16a white solid; H NMR
1
(400 MHz, chloroform-d) δ 8.20 (d, J = 477.3 Hz, 1H), 7.76−
7.67 (m, 2H), 7.47 (t, J = 7.5 Hz, 2H), 7.33 (t, J = 7.5 Hz,
2H), 7.27−7.22 (m, 2H), 2.38 (s, 6H).
Di-m-tolylphosphine oxide (1c):16a colorless oil; H NMR
1
(400 MHz, chloroform-d) δ 8.01 (d, J = 479.2 Hz, 1H), 7.58−
7.42 (m, 4H), 7.40−7.34 (m, 4H), 2.38 (s, 6H).
Bis(4-(trifluoromethyl)phenyl)phosphine oxide (1f):16b
1
pale yellow oil; H NMR (400 MHz, chloroform-d) δ 8.19
(d, J = 491.3 Hz, 1H), 7.92−7.78 (m, 8H).
Bis(4-fluorophenyl)phosphine oxide (1g):16a colorless oil;
1H NMR (400 MHz, chloroform-d) δ 8.10 (d, J = 485.9 Hz,
1H), 7.78−7.66 (m, 4H), 7.19−7.21 (m, 4H).
Bis(4-chlorophenyl)phosphine oxide (1h):16a white solid;
1H NMR (400 MHz, chloroform-d) δ 8.07 (d, J = 487.0 Hz,
1H), 7.69−7.60 (m, 4H), 7.55−7.46 (m, 4H).
Bis(4-methoxyphenyl)phosphine oxide (2i):16a white solid;
1H NMR (400 MHz, chloroform-d) δ 8.03 (d, J = 477.4 Hz,
1H), 7.65−7.56 (m, 4H), 7.00−7.10 (m, 4H), 3.85 (s, 6H).
Dibenzylphosphine oxide (1j):16b white solid; H NMR
1
(400 MHz, chloroform-d) δ 7.39−7.19 (m, 8H), 6.96 (dp, J =
468.8, 3.3 Hz, 1H), 3.18 (dt, J = 14.5, 3.6 Hz, 4H).
Dicyclohexylphosphine oxide (2k):16a white solid; 1H
NMR (400 MHz, chloroform-d) δ 6.31 (dt, J = 434.3, 2.9
Hz, 1H), 2.14−1.16 (m, 22H).
Dicyclopentylphosphine oxide (1l):16c colorless oil; 1H
NMR (400 MHz, chloroform-d) δ 6.54 (dt, J = 440.2, 3.3 Hz,
1H), 2.18−1.53 (m, 18H).
Large-Scale Synthesis. The reaction took place in an
oven-dried beaker (250 mL) equipped with a stir bar and
Bu4NI (10 mmol). The bottle was equipped with carbon
electrodes (10× 10× 3 mm) as the anode and platinum
electrodes (10× 10× 0.2 mm) as the cathode under air. H-
Phosphine oxide 1 (5 mmol) was added into bottle. Then 100
D
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Article
3057, 3013, 2947, 2920, 2848, 1646, 1591, 1439, 1226, 1182,
1130, 1113, 1035.
165.3 (dd, J = 254.0, 3.5 Hz), 134.2 (dd, J = 11.6, 8.9 Hz),
126.8 (dd, J = 142.0, 3.5 Hz), 116.0 (dd, J = 21.5, 14.4 Hz),
51.6 (d, J = 6.0 Hz); 31P NMR (162 MHz, chloroform-d) δ
31.41; HRMS (TOF MS ESI) calcd for C13H12F2O2P+ [M +
H]+ 269.0537, found 269.0537; IR (cm−1) 3100, 3063, 3037,
2970, 2950, 2850, 1738, 1659, 1592, 1500, 1400, 1365, 1301,
1226, 1160, 1129, 1112, 1033, 1014.
Methyl di-o-tolylphosphinate (3b): colorless oil, 41 mg
(78% yield); 1H NMR (400 MHz, chloroform-d) δ 7.94−7.86
(m, 2H), 7.42 (t, J = 7.5 Hz, 2H), 7.28 (td, J = 7.2, 2.6 Hz,
2H), 7.23−7.17 (m, 2H), 3.75 (d, J = 11.1 Hz, 3H), 2.36 (s,
6H); 13C NMR {1H} (101 MHz, chloroform-d) δ 141.7 (d, J =
11.1 Hz), 133.6 (d, J = 9.9 Hz), 132.3 (d, J = 2.7 Hz), 131.4
(d, J = 12.6 Hz), 129.5 (d, J = 132.5 Hz), 125.5 (d, J = 12.7
Hz), 51.0 (d, J = 5.8 Hz), 21.1 (d, J = 4.2 Hz); 31P NMR (162
MHz, chloroform-d) δ 34.12; HRMS (TOF MS ESI) calcd for
C15H18O2P+ [M + H]+ 261.1039, found 261.1042; IR (cm−1)
3058, 3014, 2947, 2846, 1738, 1595, 1455, 1382, 1279, 1219,
1143, 1078, 1031.
Methyl di-m-tolylphosphinate (3c): colorless oil, 44 mg
(84% yield); 1H NMR (400 MHz, chloroform-d) δ 7.69−7.55
(m, 4H), 7.37−7.30 (m, 4H), 3.75 (d, J = 11.1 Hz, 3H), 2.37
(s, 6H); 13C NMR {1H} (101 MHz, chloroform-d) δ 138.4 (d,
J = 13.1 Hz), 133.0 (d, J = 2.9 Hz), 132.1 (d, J = 10.2 Hz),
130.9 (d, J = 136.4 Hz), 128.7 (d, J = 10.1 Hz), 128.5 (d, J =
13.9 Hz), 51.5 (d, J = 6.0 Hz), 21.4; 31P NMR (162 MHz,
chloroform-d) δ 33.96; HRMS (TOF MS ESI) calcd for
C15H18O2P+ [M + H]+ 261.1039, found 261.1042; IR (cm−1)
3016, 2947, 2923, 2847, 2736, 1738, 1597, 1581, 1479, 1455,
1410, 1378, 1236, 1214, 1120, 1032.
Methyl di-p-tolylphosphinate (3d): colorless oil, 31 mg
(59% yield); 1H NMR (400 MHz, chloroform-d) δ 7.69 (dd, J
= 12.0, 8.0 Hz, 4H), 7.28−7.23 (m, 4H), 3.73 (d, J = 11.1 Hz,
3H), 2.38 (s, 6H); 13C NMR {1H} (101 MHz, chloroform-d)
δ 142.7 (d, J = 2.7 Hz), 131.6 (d, J = 10.5 Hz), 129.3 (d, J =
13.5 Hz), 127.9 (d, J = 139.9 Hz), 51.4 (d, J = 6.0 Hz), 21.6.
31P NMR (162 MHz, chloroform-d) δ 34.32; HRMS (TOF
MS ESI) calcd for C15H18O2P+ [M + H]+ 261.1039, found
261.1042; IR (cm−1) 3023, 2947, 2923, 2868, 2846, 2732,
1924, 1814, 1726, 1603, 1503, 1451, 1401, 1380, 1310, 1228,
1209, 1185, 1128, 1111, 1034, 1018.
Methyl bis(4-chlorophenyl)phosphinate (3h): yellow oil,
1
49 mg (81% yield); H NMR (400 MHz, chloroform-d) δ
7.76−7.70 (m, 4H), 7.48−7.43 (m, 4H), 3.77 (d, J = 11.2 Hz,
3H); 13C NMR {1H} (101 MHz, chloroform-d) δ 139.1 (d, J =
3.6 Hz), 133.0 (d, J = 11.0 Hz), 129.2 (d, J = 141.4 Hz), 129.1
(d, J = 13.9 Hz), 51.7 (d, J = 6.0 Hz); 31P NMR (162 MHz,
chloroform-d) δ 31.23; HRMS (TOF MS ESI) calcd for
C13H12Cl2O2P+ [M + H]+ 300.9946, found 300.9944; IR
(cm−1): 3082, 3052, 3021, 2948, 2847, 1738, 1585, 1482,
1391, 1231, 1130, 1087, 1034, 1013.
Methyl bis(4-methoxyphenyl)phosphinate (3i): colorless
oil, 48 mg (82% yield); 1H NMR (400 MHz, chloroform-d) δ
7.76−7.69 (m, 4H), 6.95 (dq, J = 9.3, 2.5 Hz, 4H), 3.82 (s,
6H), 3.72 (d, J = 11.2 Hz, 3H); 13C NMR {1H} (101 MHz,
chloroform-d) δ 162.6 (d, J = 3.1 Hz), 133.5 (d, J = 11.4 Hz),
122.6 (d, J = 144.7 Hz), 114.1 (d, J = 14.1 Hz), 55.3, 51.3 (d, J
= 5.9 Hz); 31P NMR (162 MHz, chloroform-d) δ 34.14;
HRMS (TOF MS ESI) calcd for C15H18O4P+ [M + H]+
293.0937, found 293.0941; IR (cm−1) 3068, 3005, 2970, 2947,
2841, 1738, 1598, 1571, 1505, 1462, 1442, 1409, 1365, 1296,
1256, 1218, 1179, 1130, 1116, 1028.
Methyl dibenzylphosphinate (3j): white solid; mp 68−73
°C, 31 mg (60% yield); 1H NMR (400 MHz, chloroform-d) δ
7.35−7.20 (m, 10H), 3.56 (d, J = 10.5 Hz, 3H), 3.08 (d, J =
16.3 Hz, 4H); 13C NMR {1H} (101 MHz, chloroform-d) δ
131.3 (d, J = 7.6 Hz), 129.9 (d, J = 5.8 Hz), 128.7 (d, J = 2.6
Hz), 127.0 (d, J = 3.1 Hz), 51.9 (d, J = 7.0 Hz), 35.6 (d, J =
86.9 Hz); 31P NMR (162 MHz, chloroform-d) δ 49.22; HRMS
(TOF MS ESI) calcd for C15H18O2P+ [M + H]+ 261.1039,
found 261.1042; IR (cm−1) 3086, 3062, 3029, 3005, 2970,
2950, 2907, 2848, 1738, 1602, 1496, 1455, 1403, 1365, 1229,
1217, 1130, 1039.
Methyl dicyclohexylphosphinate (3k): colorless oil, 40 mg
(82% yield); 1H NMR (400 MHz, chloroform-d) δ 3.72 (d, J =
9.8 Hz, 3H), 2.01−1.14 (m, 22H); 13C NMR {1H} (101 MHz,
chloroform-d) δ 52.0 (d, J = 7.0 Hz), 36.0 (d, J = 88.5 Hz),
26.3 (d, J = 13.6 Hz), 25.9 (d, J = 1.1 Hz), 25.3 (dd, J = 5.5,
3.4 Hz); 31P NMR (162 MHz, chloroform-d) δ 59.90; HRMS
(TOF MS ESI) calcd for C13H26O2P+ [M + H]+ 245.1665,
found 245.1672; IR (cm−1) 2929, 2853, 1738, 1449, 1365,
1277, 1223, 1191, 1120, 1051, 1036.
Methyl bis(3,5-dimethylphenyl)phosphinate (3e): color-
1
less oil, 42 mg (73% yield); H NMR (400 MHz, chloroform-
d) δ 7.42 (d, J = 12.5 Hz, 4H), 7.14 (s, 2H), 3.74 (d, J = 11.1
Hz, 3H), 2.33 (s, 12H); 13C NMR {1H} (101 MHz,
chloroform-d) δ 138.2 (d, J = 13.7 Hz), 133.9 (d, J = 2.9
Hz), 130.8 (d, J = 135.6 Hz), 129.2 (d, J = 10.1 Hz), 51.4 (d, J
= 6.1 Hz), 21.2; 31P NMR (162 MHz, chloroform-d) δ 34.49;
HRMS (TOF MS ESI) calcd for C17H22O2P+ [M + H]+
289.1352, found 289.1353; IR (cm−1) 3029, 2998, 2946, 2919,
2860, 2734, 1805, 1736, 1601, 1456, 1422, 1379, 1277, 1224,
1131, 1034, 994.
Methyl bis(4-(trifluoromethyl)phenyl)phosphinate (3f):
colorless oil, 56 mg (76% yield); 1H NMR (400 MHz,
chloroform-d) δ 7.97 (dd, J = 12.0, 8.0 Hz, 4H), 7.75 (dd, J =
8.2, 2.7 Hz, 4H), 3.84 (d, J = 11.2 Hz, 3H); 13C NMR {1H}
(101 MHz, chloroform-d) δ 134.6 (d, J = 138.0 Hz), 134.4
(dd, J = 32.9, 3.0 Hz), 132.2 (d, J = 10.5 Hz), 125.7 (dq, J =
Methyl dicyclopentylphosphinate (3l): colorless oil, 33 mg
(75% yield); 1H NMR (400 MHz, chloroform-d) δ 3.74 (d, J =
9.8 Hz, 3H), 2.18−2.02 (m, 2H), 1.96−1.53 (m, 16H); 13C
NMR {1H} (101 MHz, chloroform-d) δ 51.9 (d, J = 6.9 Hz),
37.1 (d, J = 92.9 Hz), 26.8−26.5 (m), 26.4 (dd, J = 10.3, 2.4
Hz); 31P NMR (162 MHz, chloroform-d) δ 63.18; HRMS
(TOF MS ESI) calcd for C11H22O2P+ [M + H]+ 217.1352,
found 217.1355; IR (cm−1) 2955, 2870, 2620, 1718, 1634,
1618, 1452, 1365, 1262, 1201, 1039.
Dibutyl methyl phosphate (3m): white solid; mp 66−69
°C, 14 mg (30% yield); 1H NMR (400 MHz, chloroform-d) δ
4.05 (q, J = 6.7 Hz, 4H), 3.76 (d, J = 11.1 Hz, 3H), 1.71−1.63
(m, 4H), 1.48−1.36 (m, 4H), 0.94 (t, J = 7.4 Hz, 6H); 13C
NMR {1H} (101 MHz, chloroform-d) δ 67.5 (d, J = 6.0 Hz),
54.1 (d, J = 6.0 Hz), 32.3 (d, J = 6.8 Hz), 18.7, 13.6; 31P NMR
13.3, 3.7 Hz), 123.4 (q, J = 273.7 Hz), 52.0 (d, J = 6.1 Hz); 31
P
NMR (162 MHz, chloroform-d) δ 29.35; HRMS (TOF MS
ESI) calcd for C15H12F6O2P+ [M + H]+ 369.0474, found
369.0473; IR (cm−1): 3046, 2954, 2853, 1938, 1738, 1679,
1614, 1505, 1461, 1401, 1324, 1238, 1171, 1131, 1107, 1063,
1036, 1017.
Methyl bis(4-fluorophenyl)phosphinate (3g): colorless oil,
1
45 mg (83% yield); H NMR (400 MHz, chloroform-d) δ
7.86−7.77 (m, 4H), 7.16 (tq, J = 9.3, 2.5 Hz, 4H), 3.77 (d, J =
11.2 Hz, 3H); 13C NMR {1H} (101 MHz, chloroform-d) δ
E
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The Journal of Organic Chemistry
Article
(162 MHz, chloroform-d) δ 0.37; HRMS (TOF MS ESI) calcd
for C9H22O4P+ [M + H]+ 225.1250, found 225.1249; IR
(cm−1) 2960, 2875, 1738, 1464, 1365, 1281, 1230, 1217, 1120,
1030.
Hz), 70.7 (d, J = 6.3 Hz), 29.3 (d, J = 6.9 Hz), 18.9; 31P NMR
(162 MHz, chloroform-d) δ 30.96; HRMS (TOF MS ESI)
calcd for C16H20O2P+ [M + H]+ 275.1195, found 275.1195; IR
(cm−1) 3077, 3015, 2961, 2875, 1738, 1592, 1470, 1367, 1228,
1130, 1071.
Pentyl diphenylphosphinate (4h): colorless oil, 32 mg
(55% yield); 1H NMR (400 MHz, chloroform-d) δ 7.84−7.76
(m, 4H), 7.53−7.40 (m, 6H), 4.01 (q, J = 6.7 Hz, 2H), 1.76−
1.67 (m, 2H), 1.42−1.23 (m, 4H), 0.87 (t, J = 7.1 Hz, 3H);
13C NMR {1H} (101 MHz, chloroform-d) δ 132.1 (d, J = 2.8
Hz), 131.6 (d, J = 138.4 Hz), 131.6 (d, J = 10.1 Hz), 128.5 (d,
J = 13.1 Hz), 65.0 (d, J = 6.1 Hz), 30.2 (d, J = 6.6 Hz), 27.7,
22.2, 14.0; 31P NMR (162 MHz, chloroform-d) δ 31.20;
HRMS (TOF MS ESI) calcd for C17H22O2P+ [M + H]+
289.1352, found 289.1351; IR (cm−1) 3077, 3058, 2956, 2931,
1738, 1592, 1466, 1378, 1229, 1113, 1071.
Ethyl diphenylphosphinate (4a): colorless oil, 38 mg (78%
1
yield); H NMR (400 MHz, chloroform-d) δ 7.86−7.78 (m,
4H), 7.54−7.41 (m, 6H), 4.11 (p, J = 7.1 Hz, 2H), 1.37 (t, J =
7.0 Hz, 3H); 13C NMR {1H} (101 MHz, chloroform-d) δ
132.1 (d, J = 2.7 Hz), 131.6 (d, J = 137.4 Hz), 131.6 (d, J =
10.1 Hz), 128.5 (d, J = 13.1 Hz), 61.1 (d, J = 5.8 Hz), 16.5 (d,
J = 6.6 Hz); 31P NMR (162 MHz, chloroform-d) δ 31.38;
HRMS (TOF MS ESI) calcd for C14H16O2P+ [M + H]+
247.0882, found 247.0883; IR (cm−1) 3077, 3058, 2982, 2855,
1737, 1678, 1592, 1485, 1392, 1227, 1130, 1114, 1034.
Ethyl bis(3,5-dimethylphenyl)phosphinate (4b): white
1
solid; mp 74−79 °C, 44 mg (73% yield); H NMR (400
MHz, chloroform-d) δ 7.43 (d, J = 12.4 Hz, 4H), 7.12 (s, 2H),
4.13−4.04 (m, 2H), 2.33 (s, 12H), 1.37 (t, J = 7.0 Hz, 3H);
13C NMR {1H} (101 MHz, chloroform-d) δ 138.2 (d, J = 13.7
Hz), 133.8 (d, J = 2.9 Hz), 131.5 (d, J = 135.4 Hz), 129.1 (d, J
Cyclopropylmethyl diphenylphosphinate (4i): colorless oil,
1
31 mg (56% yield); H NMR (400 MHz, chloroform-d) δ
7.87−7.79 (m, 4H), 7.55−7.41 (m, 6H), 3.89 (t, J = 7.4 Hz,
2H), 1.23−1.14 (m, 1H), 0.58−0.52 (m, 2H), 0.29−0.24 (m,
2H); 13C NMR {1H} (101 MHz, chloroform-d) δ 132.1 (d, J =
2.8 Hz), 131.8 (d, J = 137.4 Hz), 131.7 (d, J = 10.1 Hz), 128.5
(d, J = 13.1 Hz), 69.9 (d, J = 5.8 Hz), 11.5 (d, J = 7.2 Hz), 3.6;
31P NMR (162 MHz, chloroform-d) δ 31.13; HRMS (TOF
MS ESI) calcd for C16H18O2P+ [M + H]+ 273.1039, found
273.1037; IR (cm−1) 3058, 3010, 2945, 2885, 1737, 1592,
1485, 1365, 1280, 1130, 1071.
Cyclopentyl diphenylphosphinate (4j): white solid; mp
108−113 °C, 29 mg (51% yield); 1H NMR (400 MHz,
chloroform-d) δ 7.85−7.76 (m, 4H), 7.54−7.40 (m, 6H),
4.92−4.85 (m, 1H), 1.96−1.87 (m, 2H), 1.85−1.73 (m, 4H),
1.64−1.53 (m, 2H); 13C NMR {1H} (101 MHz, chloroform-d)
δ 132.3 (d, J = 137.4 Hz), 132.0 (d, J = 2.8 Hz), 131.6 (d, J =
10.1 Hz), 128.4 (d, J = 13.1 Hz), 78.9 (d, J = 6.3 Hz), 34.3 (d,
J = 4.2 Hz), 23.1; 31P NMR (162 MHz, chloroform-d) δ 30.07;
HRMS (TOF MS ESI) calcd for C17H20O2P+ [M + H]+
287.1195, found 287.1193; IR (cm−1) 3077, 3014, 2963, 2872,
1737, 1592, 1484, 1366, 1220, 1168, 1114, 1073.
= 10.1 Hz), 61.0 (d, J = 5.8 Hz), 21.3, 16.6 (d, J = 6.5 Hz); 31
P
NMR (162 MHz, chloroform-d) δ 32.62; HRMS (TOF MS
ESI) calcd for C18H24O2P+ [M + H]+ 303.1508, found
303.1513; IR (cm−1) 3030, 2979, 2921, 2861, 1738, 1601,
1443, 1276, 1163, 1097, 993.
Propyl diphenylphosphinate (4c): white solid; mp 80−84
°C, 37 mg (70% yield); 1H NMR (400 MHz, chloroform-d) δ
7.86−7.78 (m, 4H), 7.54−7.41 (m, 6H), 3.99 (q, J = 6.7 Hz,
2H), 1.81−1.70 (m, 2H), 1.01−0.95 (m, 2H); 13C NMR {1H}
(101 MHz, chloroform-d) δ 132.1 (d, J = 2.8 Hz), 131.7 (d, J =
137.4 Hz), 131.6 (d, J = 10.1 Hz), 128.5 (d, J = 13.1 Hz), 66.5
(d, J = 6.1 Hz), 23.9 (d, J = 6.7 Hz), 10.2; 31P NMR (162
MHz, chloroform-d) δ 31.14; HRMS (TOF MS ESI) calcd for
C15H18O2P+ [M + H]+ 261.1039, found 261.1039; IR (cm−1)
3058, 3015, 2969, 1738, 1592, 1484, 1365, 1227, 1113, 1058.
Isopropyl diphenylphosphinate (4d): white solid; mp 86−
1
89 °C, 19 mg (36% yield); H NMR (400 MHz, chloroform-
d) δ 7.86−7.78 (m, 4H), 7.53−7.40 (m, 6H), 4.74−4.62 (m,
1H), 1.35 (d, J = 6.1 Hz, 6H); 13C NMR {1H} (101 MHz,
chloroform-d) δ 132.4 (d, J = 138.4 Hz), 131.9 (d, J = 2.7 Hz),
131.6 (d, J = 10.0 Hz), 128.4 (d, J = 13.0 Hz), 70.2 (d, J = 6.0
Hz), 24.3 (d, J = 4.1 Hz); 31P NMR (162 MHz, chloroform-d)
δ 29.80; HRMS (TOF MS ESI) calcd for C15H18O2P+ [M +
H]+ 261.1039, found 261.1038; IR (cm−1) 3058, 3015, 2972,
2929, 1738, 1592, 1465, 1440, 1386, 1219, 1178, 1118, 1100,
1002.
2,2,2-Trifluoroethyl diphenylphosphinate (4l): white solid;
1
mp 89−94 °C, 39 mg (65% yield); H NMR (400 MHz,
chloroform-d) δ 7.85−7.78 (m, 4H), 7.59−7.44 (m, 6H), 4.33
(qd, J = 8.1, 6.7 Hz, 2H); 13C NMR {1H} (101 MHz,
chloroform-d) δ 132.9 (d, J = 2.9 Hz), 131.6 (d, J = 10.6 Hz),
129.8 (d, J = 137.3 Hz), 128.8 (d, J = 13.5 Hz), 123.0 (qd, J =
278.6, 10.4 Hz), 60.9 (qd, J = 37.7, 4.7 Hz); 31P NMR (162
MHz, chloroform-d) δ 35.19; HRMS (TOF MS ESI) calcd for
C14H13F3O2P+ [M + H]+ 301.0600, found 301.0600; IR
(cm−1) 3061, 3016, 2970, 2855, 1738, 1593, 1486, 1440, 1366,
1286, 1132, 1080.
Butyl diphenylphosphinate (4e): colorless oil, 36 mg (65%
1
yield); H NMR (400 MHz, chloroform-d) δ 7.85−7.78 (m,
4H), 7.54−7.41 (m, 6H), 4.03 (q, J = 6.6 Hz, 2H), 1.75−1.67
(m, 2H), 1.49−1.38 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H); 13C
NMR {1H} (101 MHz, chloroform-d) δ 132.1 (d, J = 2.6 Hz),
131.7 (d, J = 137.4 Hz), 131.6 (d, J = 10.0 Hz), 128.5 (d, J =
13.1 Hz), 64.7 (d, J = 6.0 Hz), 32.6 (d, J = 6.6 Hz), 18.9, 13.6;
31P NMR (162 MHz, chloroform-d) δ 31.14; HRMS (TOF
MS ESI) calcd for C16H20O2P+ [M + H]+ 275.1195, found
275.1195; IR (cm−1) 3016, 2970, 2874, 1739, 1591, 1441,
1365, 1218, 1114, 1063, 985.
1,1,1,3,3,3-Hexafluoropropan-2-yl diphenylphosphinate
1
(4m): white solid; mp 58−63 °C, 26 mg (35% yield); H
NMR (400 MHz, chloroform-d) δ 7.82−7.74 (m, 4H), 7.63−
7.46 (m, 6H), 5.49−5.34 (m, 1H); 13C NMR {1H} (101 MHz,
chloroform-d) δ 133.2 (d, J = 2.9 Hz), 131.5 (d, J = 11.2 Hz),
129.6 (d, J = 137.2 Hz), 128.7 (d, J = 13.9 Hz), 120.7(q, J =
282.8 Hz), 69.2−67.7 (m); 31P NMR (162 MHz, chloroform-
d) δ 39.90; HRMS (TOF MS ESI) calcd for C15H11F6NaO2P+
[M+ Na]+ 391.0293, found 391.0293; IR (cm−1) 3063, 3017,
2946, 2856, 1738, 1594, 1486, 1440, 1382, 1293, 1199, 1133,
1109.
Isobutyl diphenylphosphinate (4f): white solid; mp 64−68
°C, 32 mg (59% yield); 1H NMR (400 MHz, chloroform-d) δ
7.85−7.78 (m, 4H), 7.55−7.42 (m, 6H), 3.79 (t, J = 6.3 Hz,
2H), 2.07−1.96 (m, 1H), 0.97 (d, J = 6.7 Hz, 6H); 13C NMR
{1H} (101 MHz, chloroform-d) δ 132.1 (d, J = 2.8 Hz), 131.6
(d, J = 137.4 Hz), 131.6 (d, J = 10.1 Hz), 128.5 (d, J = 13.1
F
DOI: 10.1021/acs.joc.8b02882
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The Journal of Organic Chemistry
Article
(8) (a) 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. (b) Dhineshkumar, J.; Prabhu, K. R. Cross-Hetero-
Dehydrogenative Coupling Reaction of Phosphites: a Catalytic Metal-
Free Phosphorylation of Amines and Alcohols. Org. Lett. 2013, 15,
6062.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.8b02882.
■
S
Full spectroscopic data for compounds 3 and 4; copies
1
of H NMR and 13C NMR spectra (PDF)
(9) For selected recent reviews, see: (a) Meyer, T. H.; Oliveira, J. C.
A.; Sau, S. C.; Ang, N. W. J.; Ackermann, L. Electrooxidative Allene
Annulations by Mild Cobalt-Catalyzed C−H Activation. ACS Catal.
2018, 8, 9140. (b) Yoshida, J. i.; Kataoka, K.; Horcajada, R.; Nagaki,
A. Modern Strategies in Electroorganic Synthesis. Chem. Rev. 2008,
108, 2265. (c) Moeller, K. D. Using Physical Organic Chemistry to
Shape the Course of Electrochemical Reactions. Chem. Rev. 2018,
118, 4817. (d) Sperry, J. B.; Wright, D. L. The Application of
Cathodic Reductions and Anodic Oxidations in the Synthesis of
Complex Molecules. Chem. Soc. Rev. 2006, 35, 605. (e) Yan, M.;
Kawamata, Y.; Baran, P. S. Synthetic Organic Electrochemical
Methods Since 2000: on the Verge of a Renaissance. Chem. Rev.
2017, 117, 13230. (f) Yoshida, J. i.; Shimizu, A.; Hayashi, R.
Electrogenerated Cationic Reactive Intermediates: The Pool Method
and Further Advances. Chem. Rev. 2018, 118, 4702. (g) Jiang, Y.; Xu,
K.; Zeng, C. Use of Electrochemistry in the Synthesis of Heterocyclic
Structures. Chem. Rev. 2018, 118, 4485. (h) Tang, S.; Liu, Y.; Lei, A.
Electrochemical Oxidative Cross-Coupling with Hydrogen Evolution:
A Green and Sustainable Way for Bond Formation. Chem. 2018, 4,
AUTHOR INFORMATION
Corresponding Author
*E-mail: hanjl@nju.edu.cn, hanjl@njfu.edu.cn.
ORCID
Jianlin Han: 0000-0002-3817-0764
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 21761132021).
Support from the Changzhou Jin-Feng-Huang program (for
Han) is also acknowledged.
̈
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