Electrophilic Fluorination of Secondary Phosphine Oxides and Its Application to P-O Bond Construction

Article abstract of DOI:10.1021/acs.joc.6b01932

A novel and efficient electrophilic fluorination of secondary phosphine oxides with Selectfluor has been achieved. This transformation provides direct access to phosphoric fluorides in up to 92% yield under mild conditions. In addition, P-O bond construction via a one-pot coupling process of secondary phosphine oxides with water or alcohols in the presence of Selectfluor leads to the formation of phosphinic acids or phosphinates in up to 96% yield.

Full text of DOI:10.1021/acs.joc.6b01932

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Note
Electrophilic Fluorination of Secondary Phosphine
Oxides and Its Application to P-O Bond Construction
Qian Chen, Jiekun Zeng, Xinxing Yan, Yulin Huang, Chunxiao Wen, Xingguo Liu, and Kun Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01932 • Publication Date (Web): 23 Sep 2016
Downloaded from http://pubs.acs.org on September 25, 2016
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Electrophilic Fluorination of Secondary Phosphine
Oxides and Its Application to P−O Bond Construction
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Qian Chen,* Jiekun Zeng, Xinxing Yan, Yulin Huang, Chunxiao Wen, Xingguo Liu, and Kun Zhang
School of Chemical Engineering and Light Industry, Guangdong University of Technology,
Guangzhou, Guangdong 510006, China
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
ABSTRACT: A novel and efficient electrophilic fluorination of secondary phosphine oxides with
Selectfluor has been achieved. This transformation provides direct access to phosphoric fluorides in up
to 92% yield under mild conditions. In addition, P−O bond construction via a oneꢀpot coupling process
of secondary phosphine oxides with water or alcohols in the presence of Selectfluor leads to the
formation of phosphinic acids or phosphinates in up to 96% yield.
Organophosphorus compounds bearing a P
−F bond have been of general interest due to their
particular applications in enzymatic reactions as mechanistic probes or potent inhibitors.1−5
A
variety of methods for P F bond construction from various phosphoric substrates using special
−
fluorinating reagents have been reported, while harsh reaction conditions, toxic, expensive,
unstable and moistureꢀsensitive reagents, or long reaction times are generally required.6 The
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nucleophilic fluorination of P(O)ꢀH compounds using fluoride ions as fluoride sources are
popularly used for constructing P F bonds (Scheme 1). Kaushik, Dubey and coꢀworkers reported
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a oneꢀpot synthesis of dialkyl fluorophosphates via in situ formation of dialkyl chlorophosphates
from dialkyl phosphites with dichlorodimethylhydantoinꢀKF, trichloroacetonitrileꢀKF or CuCl2ꢀ
CsF as the fluorinating reagent (eq 1).7 Recently, Yang and coꢀworkers developed an efficient
copperꢀpromoted oxidativeꢀfluorination of P(O)ꢀH compounds using NaF as the fluorinating
reagent and DDQ as the oxidant (eq 2).8 However, these methods require the assistance of a
source of chlorine or an additional oxidant with a copper catalyst because the weak
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nucleophilicity of fluoride ions limits access to P F bonds via direct nucleophilic substitution
−
reactions. Thus, the development of a direct protocol for the preparation of phosphoric fluorides
under milder conditions is still a significant issue.
Scheme 1. Overview of the Fluorination of P(O)-H Compounds
Previous work: nucleophilic fluorination
DCDMH
or CCl3CN
or CuCl2
O
P
H
O
P
O
P
F
KF or CsF
(1)
(2)
RO
OR
RO
OR
RO
OR
Cl
R1
HO
P
R2
O
cat. CuBr2
DDQ
O
O
NaF
Cl
Cl
CN
R1
P
R2
R1
P
F
R2
H
CN
R1, R2 = aryl, alkoxyl
O
CuBr2
This work: electrophilic fluorination
O
O
SelectFluor
(3)
R
P
H
R
R
P
F
R
CH3CN, RT
R = aryl, alkyl
Electrophilic fluorinating reagents have attracted much attention due to their great
applications in fluorination reactions.9 For example,
Nꢀfluorobis(benzenesulfonyl)imide (NFSI)
or 1ꢀchloromethylꢀ4ꢀfluorodiazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor)
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provides a convenient entry to siteꢀselective monofluorination.9,10 Most recently, our group
achieved an efficient oxidation protocol for triarylphosphines with Selectfluor to form
triarylphosphine oxides, which were generated via a hydration of unstable fluoroꢀphosphonium
cation intermediates and a subsequent elimination of HF.11 We then became interested in
studying P−F bond construction through direct electrophilic substitution of P(O)ꢀH compounds
with electrophilic fluorinating reagents. We envisioned that the interaction between P(O)ꢀH
compounds and NFSI/Selectfluor might produce phosphoric fluorides via the corresponding
fluoroꢀphosphonium cations. Herein, we report an efficient electrophilic fluorination of
secondary phosphine oxides to afford phosphoric fluorides under mild conditions (eq 3), and a
oneꢀpot coupling process of secondary phosphine oxides with water or alcohols in the presence
of Selectfluor was further investigated.
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To test the hypothesis, we first examined the reaction of diphenylphosphine oxide 1a with
NFSI in CH3CN at room temperature, while only trace amounts of the desired
diphenylphosphinic fluoride 2a was detected. When the reaction temperature was raised to 60 oC,
2a was isolated in only 14% yield. To our delight, when the fluorinating reagent was switched
from NSFI to Selectfluor, the reaction proceeded smoothly at room temperature to lead to the
formation of 2a in 91% yield. We then turned to screen other solvents. The use of THF, ethanol,
or DCM did not give the desired product, and the use of DME afforded 2a in a low yield of only
25%. It is noteworthy that the fluorination reaction in aqueous CH3CN under an air atmosphere
also smoothly gave 2a in high yield.
To investigate the scope of the fluorination protocol, we applied the reaction conditions to a
variety of P(O)ꢀH compounds, and the results are illustrated in Scheme 2. For the reaction of
diarylphosphine oxides with Selectfluor, both electronꢀdonating groups and electronꢀ
withdrawing groups on the aromatic rings were all well tolerated, and the corresponding
fluorides 2a
−
2g were isolated in 62 92% yields. It is noteworthy that the reaction of
−
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sterically hindered di(naphthalenꢀ1ꢀyl)phosphine oxide with bulky Selectfluor also successfully
afforded the desired fluoride 2h in 89% yield although more reaction time (5 h) was required.
When dibenzylphosphine oxides were employed, 2i and 2j were obtained in moderate yields.
Dihexylphosphine oxide gave the desired fluoride 2l in only 32% yield, while
dicyclopentylphosphine oxide failed to produce the corresponding product 2k. We then turned
to the fluorination of phosphite esters. The reaction of diphenyl phosphite with Selectfluor gave
the desired fluoride 2m in a low yield of 20%, and dibenzyl/diethyl phosphite failed to produce
the corresponding products 2n and 2o. The difference in the fluorination between arylphosphine
oxides and alkylphosphine oxides/phosphite esters might be explained by their nucleophilicity
abilities.
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Scheme 2. Fluorination of P(O)-H Compoundsa,b
aReaction conditions: 1 (0.2 mmol), Selectfluor (0.22 mmol) in CH3CN (2 mL) stirring at RT. bIsolated yield.
In comparison with phosphinic chlorides/bromides, phosphinic fluorides are neither air nor moisture
sensitive. However, much less attention has been paid to the synthetic utility of phosphinic fluorides12
probably due to the toxicity of fluorides. We then turned to study the reactivity of phosphoric
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fluorides. Diphenylphosphinic fluoride 2a was smoothly hydrolyzed in the presence of Cs2CO3 in
aqueous CH3CN at 60 oC to produce diphenylphosphinic acid 3a in 75% yield.12 Thus, we then tried to
carry out a oneꢀpot coupling reaction of diphenylphosphine oxide 1a with water in the presence of
Selectfluor. To our delight, the reaction gave the desired acid 3a in 96% yield. As a comparison, the
traditional protocol for the preparation of phosphinic acids and phosphinates from P(O)ꢀH compounds
mainly rely on the AthertonꢀTodd reaction,13 which usually requires the use of the toxic
tetrachloromethane as the halogenating reagent and solvent. Thus, this oneꢀpot process via in situ
formation of phosphoric fluorides and subsequent hydrolysis or alcoholysis might provide an alternative
method for P−O bond construction. Water/alcohols and various secondary phosphine oxides were then
applied in the oneꢀpot process, and the results are illustrated in Scheme 3. When water was used as the
nucleophile, electronꢀrich and electronꢀpoor diarylphosphine oxides 1a−1h were all well tolerated for
the oneꢀpot coupling reaction to give the corresponding diarylphosphinic acids 3a−3h in 32−96% yields.
Dibenzylphosphine oxide 1i also efficiently produced the P−O coupling product 3i in 65% yield. When
methanol or ethanol served as the nucleophile, diarylphosphine oxides gave the corresponding methyl or
ethyl diarylphosphinates in moderate to excellent yields. When isopropanol was employed, the desired
3l was obtained in a low yield of 27%. The reaction of 1a with tertiary butanol under the same
conditions did not give the corresponding product 3m, but Nꢀtertꢀbutylacetamide was isolated in
quantitative yield (yield based on Selectfluor). This kind of byproduct was probably generated by the
reaction between alcohols (tertiary or benzylic alcohols) and nitriles, which is well known by the name
‘Ritter reaction’.14 In this case, Selectfluor might activate the hydroxyl group of tertiary butanol to
generate tertꢀbutyl cation followed by the electrophilic addition to acetonitrile. Similarly, benzyl alcohol
and phenol failed to give the corresponding products probably due to the disturbance of Ritter reaction.
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Scheme 3. One-Pot Coupling Reaction of P(O)-H Compounds with Water or Alcoholsa,b
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aReaction conditions: 1 (0.1 mmol), Selectfluor (0.15 mmol) in a mixed solvent of water (1 mL) or alcohols (1 mL) and
CH3CN (1 mL) stirring at 60 oC. bIsolated yield. cBnOH (5 eq) or PhOH (5 eq) was added.
To gain more insight about the mechanism of the fluorination reaction, a control experiment was
conducted for the fluorination of 1a. In the presence of radical scavenger TEMPO (2 eq), fluoride 2a
was isolated in 68% yield, while the possible TEMPO adducts were not found in the reaction mixture.
This result suggests that a singleꢀelectron transfer (SET) process15 is disfavored in this case and the
reaction involves a direct electrophilic fluorination. Thus, a plausible mechanism of the fluorination of
secondary phosphine oxides with Selectfluor is proposed as shown in Scheme 4. The less stable P(III)
form, which exists with the P(V) phosphinylidene 1 through the tautomerization,16 interacts with
Selectfluor to generate the unstable fluoroꢀphosphonium cation 4. Subsequent deprotonation gives the
desired fluoride 2. According to the proposed mechanism, it is reasonable to conclude that
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diarylphosphine oxides possess high reactivity in the fluorination reaction owing to the pꢀπ conjugated
system, which may enhance the nucleophilicity of the corresponding P(III) form. Dialkylphosphine
oxides showed lower reactivity owing to the lack of this conjugated system, and the failure to obtain
fluoride 2k might be explained by the steric hindrance between dicyclopentylphosphine oxides and
bulky Selectfluor. Dibenzyl/diethyl phosphite showed no reactivity mainly due to their low
nucleophilicity, while diphenyl phosphite showed slight reactivity depending on the electronꢀrich
aromatic rings.
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Scheme 4. Plausible Mechanism of the Fluorination Reaction
In summary, we have developed a direct electrophilic fluorination of readily available
secondary phosphine oxides with Selectfluor, which provides a highly efficient protocol for the
synthesis of phosphoric fluorides under mild conditions. To the best of our knowledge, this
finding is the first example of electrophilic fluorination of P(O)ꢀH compounds. In addition, this
fluorination has been successfully applied to the oneꢀpot coupling process of secondary
phosphine oxides with water or alcohols, which provides a simple method for P O bond
−
construction. This property of Selectfluor should lead to new and useful applications in
organophosphorus chemistry.
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Experimental Section
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General Details. All reactions were carried out using ovenꢀdried glassware and standard
syringe/septa techniques. Commercial reagents were used without purification unless otherwise noted.
Secondary phosphine oxides which were not commercially available were prepared according to the
literature.17 Petroleum ether refers to the petroleum fraction bp 40−60 °C. Flash chromatography was
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1
performed using the indicated solvent system on silica gel standard grade 60 (230−400 mesh). H NMR
spectra were recorded on a 400 MHz spectrometer. 13C NMR spectra were recorded on a 100 MHz
spectrometer. 31P NMR spectra were recorded on a 162 MHz spectrometer. 19F NMR spectra were
recorded on a 376 MHz spectrometer. Chemical shifts are reported relative to CDCl3 (δ 7.26 ppm) or d6ꢀ
DMSO (δ 2.50 ppm) for 1H NMR and CDCl3 (δ 77.16 ppm) or d6ꢀDMSO (δ 39.52 ppm) for 13C NMR.
Highꢀresolution mass spectra (HRMS) were recorded on ESIꢀTOF. The known compounds 2a8, 2b8, 2e8,
2m18, 3a19, 3c17b, 3f20, 3g21, 3i22, 3j23, 3k24, 3l23, 3p17b, 3r20, and 3t25 showed characterization data in
full agreement with previously reported data.
General Procedure for the Fluorination Reaction. To a solution of diphenylphosphine oxide 1a (40
mg, 0.2 mmol) in acetonitrile (2 mL) was added Selectfluor (78 mg, 0.22 mmol). The mixture was
stirred for 1 h at room temperature. After removal of the solvent, the residue was then purified by flash
column chromatography on silica gel with petroleum ether/ethyl acetate (2:1) to give product 2a (40 mg,
91%).
General Procedure for the Synthesis of Phosphinic Acids. To a solution of diphenylphosphine
oxide 1a (20 mg, 0.1 mmol) in 2 mL of CH3CN/H2O (v/v = 1/1) was added Selectfluor (53 mg, 0.15
mmol). The mixture was stirred at 60 °C for 12 h. After removal of the solvent, the residue was then
isolated by precipitation in chloroform to give product 3a (21 mg, 96%).
General Procedure for the Synthesis of Phosphinates. To a solution of diphenylphosphine oxide
1a (20 mg, 0.1 mmol) in 2 mL of CH3CN/MeOH (v/v = 1/1) was added Selectfluor (53 mg, 0.15
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mmol). The mixture was stirred at 60 °C for 12 h. After removal of the solvent, the residue was then
purified by flash column chromatography on silica gel with petroleum ether/ethyl acetate (2:1) to give
product 3j (22 mg, 95%).
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Diphenylphosphinic Fluoride (2a). Pale yellow oil (40 mg, 91%):8 1H NMR (400 MHz, CDCl3) δ
7.86−7.77 (m, 4H), 7.63−7.57 (m, 2H), 7.53−7.46 (m, 4H); 31P NMR (162 MHz, CDCl3) δ 40.90 (d, J =
1020 Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ75.15 (d, J = 1020 Hz); 13C NMR (100 MHz, CDCl3) δ 133.4
(d, J = 2.3 Hz), 131.4 (dd, J = 11.3, 1.9 Hz), 128.9 (d, J = 14.1 Hz), 128.8 (dd, J = 140.0, 22.3 Hz).
Di-p-tolylphosphinic Fluoride (2b). Pale yellow oil (34 mg, 68%):8 1H NMR (400 MHz, CDCl3) δ
7.73−7.65 (m, 4H), 7.32−7.27 (m, 4H), 2.40 (s, 6H); 31P NMR (162 MHz, CDCl3) δ 42.02 (d, J = 1014
Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ74.36 (d, J = 1014 Hz); 13C NMR (100 MHz, CDCl3) δ 144.0 (d, J
= 2.3 Hz), 131.4 (dd, J = 11.7, 1.8 Hz), 129.5 (d, J = 14.5 Hz), 125.8 (dd, J = 143.0, 22.0 Hz), 21.7.
Bis(4-chlorophenyl)phosphinic Fluoride (2c). White amorphous solid (36 mg, 62%): 1H NMR (400
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MHz, CDCl3) δ 7.78−7.70 (m, 4H), 7.53−7.47 (m, 4H); P NMR (162 MHz, CDCl3) δ 38.76 (d, J =
1023 Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ73.99 (d, J = 1023 Hz); 13C NMR (100 MHz, CDCl3) δ 140.5
(d, J = 3.8 Hz), 132.8 (dd, J = 12.3, 1.8 Hz), 129.4 (d, J = 14.9 Hz), 126.8 (dd, J = 144.0, 23.0 Hz);
HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C12H9Cl2FOP 288.9747; Found 288.9749.
Bis(4-fluorophenyl)phosphinic Fluoride (2d). White amorphous solid (34 mg, 66%): 1H NMR (400
31
MHz, CDCl3) δ 7.88−7.78 (m, 4H), 7.25−7.18 (m, 4H); P NMR (162 MHz, CDCl3) δ 38.83 (d, J =
1019 Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ72.95 (d, J = 1019 Hz), ꢀ103.26; 13C NMR (100 MHz,
CDCl3) δ 166.0 (dd, J = 254.0, 4.0 Hz), 134.2 (ddd, J = 12.8, 9.2, 2.0 Hz), 124.6 (ddd, J = 147.1, 23.7,
3.0 Hz), 116.5 (dd, J = 21.7, 15.5 Hz); HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C12H9F3OP
257.0338; Found 257.0342.
Di-m-tolylphosphinic Fluoride (2e). Colorless oil (39 mg, 79%):8 1H NMR (400 MHz, CDCl3) δ
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7.69−7.55 (m, 4H), 7.43−7.34 (m, 4H), 2.39 (s, 6H); P NMR (162 MHz, CDCl3) δ 41.63 (d, J = 1019
Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ75.47 (d, J = 1019 Hz); 13C NMR (100 MHz, CDCl3) δ 138.8
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(d, J = 14.0 Hz), 134.1 (d, J = 2.8 Hz), 131.8 (dd, J = 11.3, 1.9 Hz), 128.8 (dd, J =140.0, 22.0 Hz), 128.7
(d, J = 14.8 Hz), 128.5 (dd, J = 11.3, 1.9 Hz), 21.3.
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Bis(3-methoxyphenyl)phosphinic Fluoride (2f). Colorless oil (35 mg, 62%): H NMR (400 MHz,
CDCl3) δ 7.44−7.31 (m, 6H), 7.15−7.09 (m, 2H), 3.82 (s, 6H); 31P NMR (162 MHz, CDCl3) δ 40.69 (d,
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J = 1022 Hz); F NMR (376 MHz, CDCl3) δ ꢀ75.06 (d, J = 1022 Hz); C NMR (100 MHz, CDCl3) δ
159.7 (d, J = 17.7 Hz), 130.2 (d, J = 16.7 Hz), 129.9 (dd, J = 139.0, 22.0 Hz), 123.6 (dd, J = 11.1, 1.9
Hz), 119.6 (d, J = 2.8 Hz), 116.1 (dd, J = 12.7, 1.9 Hz), 55.5; HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd
for C14H15FO3P 281.0737; Found 281.0736.
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Bis(3,5-dimethylphenyl)phosphinic Fluoride (2g). White amorphous solid (51 mg, 92%): H NMR
(400 MHz, CDCl3) δ 7.42 (d, J = 13.4 Hz, 4H), 7.22 (s, 2H), 2.35 (s, 12H); 31P NMR (162 MHz,
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CDCl3) δ 42.32 (d, J = 1018 Hz); F NMR (376 MHz, CDCl3) δ ꢀ75.93 (d, J = 1018 Hz); C NMR
(100 MHz, CDCl3) δ 138.6 (d, J = 14.7 Hz), 135.0 (d, J = 2.6 Hz), 128.9 (dd, J = 11.3, 1.8 Hz), 128.8
(dd, J =138.0, 22.0 Hz), 21.2; HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C16H19FOP 277.1152; Found
277.1155.
Di(naphthalen-1-yl)phosphinic Fluoride (2h). White amorphous solid (57 mg, 89%): 1H NMR (400
MHz, CDCl3) δ 8.58−8.51 (m, 2H), 8.10 (d, J = 8.2 Hz, 2H), 8.03 (dd, J = 17.0, 7.1 Hz, 2H), 7.96−7.89
(m, 2H), 7.60−7.48 (m, 6H); 31P NMR (162 MHz, CDCl3) δ 44.48 (d, J = 1019 Hz); 19F NMR (376
13
MHz, CDCl3) δ ꢀ67.94 (d, J = 1019 Hz); C NMR (100 MHz, CDCl3) δ 134.6 (d, J = 3.1 Hz), 133.9
(dd, J = 12.0, 3.9 Hz), 133.6 (d, J = 11.3 Hz), 132.7 (d, J = 10.9 Hz), 129.1 (d, J = 1.5 Hz), 128.1, 126.9,
126.3 (d, J = 6.0 Hz), 125.6 (dd, J = 137.0,19.0 Hz), 124.6 (d, J = 16.2 Hz); HRMS (ESIꢀTOF) m/z: [M
+ H]+ Calcd for C20H15FOP 321.0839; Found 321.0836.
1
Dibenzylphosphinic Fluoride (2i). White amorphous solid (21 mg, 42%): H NMR (400 MHz,
CDCl3) δ 7.31−7.13 (m, 10H), 3.15 (dd, J = 16.0, 8.0 Hz, 4H); 31P NMR (162 MHz, CDCl3) δ 58.57 (d,
19
13
J = 1041 Hz); F NMR (376 MHz, CDCl3) δ ꢀ76.71 (d, J = 1041 Hz); C NMR (100 MHz, CDCl3) δ
129.8 (d, J = 6.3 Hz), 129.2 (d, J = 7.3 Hz), 129.0 (d, J = 2.7 Hz), 127.6 (d, J = 3.3 Hz), 34.8 (dd, J
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= 85.9, 14.5 Hz); HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C14H15FOP 249.0839; Found 249.0845.
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3
1
Bis(4-fluorobenzyl)phosphinic Fluoride (2j). White amorphous solid (33 mg, 58%): H NMR (400
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5
6
31
MHz, CDCl3) δ 7.22−7.15 (m, 4H), 7.03 (t, J = 8.4 Hz, 4H), 3.20 (dd, J = 16.0, 4.0 Hz, 4H); P NMR
(162 MHz, CDCl3) δ 57.67 (d, J = 1042 Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ76.88 (d, J = 1042 Hz), ꢀ
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114.36; C NMR (100 MHz, CDCl3) δ 162.3 (dd, J = 247.1, 3.6 Hz), 131.5–131.2 (m), 124.8–124.6
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(m), 116.0 (dd, J = 21.7, 2.6 Hz), 34.0 (dd, J = 86.6, 14.8 Hz); HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd
for C14H13F3OP 285.0651; Found 285.0650.
1
Dihexylphosphinic Fluoride (2l). White amorphous solid (15 mg, 32%): H NMR (400 MHz,
CDCl3) δ 1.89−1.77 (m, 4H), 1.69−1.57 (m, 4H), 1.45−1.36 (m, 4H), 1.34−1.25 (m, 8H), 0.88 (t, J = 6.4
Hz, 6H); 31P NMR (162 MHz, CDCl3) δ 70.46 (d, J = 1016 Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ78.22
13
(d, J = 1016 Hz); C NMR (100 MHz, CDCl3) δ 31.2, 30.2 (d, J = 14.7 Hz), 27.8 (dd, J = 87.8, 14.5
Hz), 22.3, 21.2 (d, J = 4.4 Hz), 13.9; HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C12H27FOP 237.1778;
Found 237.1787.
Diphenyl Phosphorofluoridate (2m). Colorless oil (10 mg, 20%):18 1H NMR (400 MHz, CDCl3) δ
7.42−7.36 (m, 4H), 7.29−7.21 (m, 6H); 31P NMR (162 MHz, CDCl3) δ ꢀ21.49 (d, J = 1002 Hz); 19F
13
NMR (376 MHz, CDCl3) δ ꢀ77.83 (d, J = 1002 Hz); C NMR (100 MHz, CDCl3) δ 149.8 (d, J = 7.1
Hz), 130.1, 126.3, 119.8 (d, J = 4.9 Hz).
Diphenylphosphinic Acid (3a). White amorphous solid (21 mg, 96%):19 1H NMR (400 MHz, CDCl3)
δ 7.74−7.69 (m, 4H), 7.46−7.43 (m, 2H), 7.37−7.32 (m, 4H), 7.06 (brs, 1H); 31P NMR (162 MHz,
CDCl3) δ 32.65; 13C NMR (100 MHz, CDCl3) δ 132.9 (d, J = 139.4 Hz), 131.9 (d, J = 2.7 Hz), 131.4 (d,
J = 10.5 Hz), 128.4 (d, J = 13.3 Hz).
Di-p-tolylphosphinic Acid (3b). White amorphous solid (19 mg, 77%): 1H NMR (400 MHz, CDCl3)
δ 8.51 (s, 1H), 7.62−7.55(m, 4H), 7.19−7.08 (m, 4H), 2.34 (s, 6H); 31P NMR (162 MHz, CDCl3) δ 33.25;
13C NMR (100 MHz, CDCl3) δ 142.0 (d, J = 2.7 Hz), 131.2 (d, J = 10.9 Hz), 129.8 (d, J = 142.0 Hz),
128.9 (d, J = 13.8 Hz), 21.6; HRMS (ESIꢀTOF) m/z: [M + 2Na ꢀ H]+ Calcd for C14H14O2PNa2
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291.0521; Found 291.0532.
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Bis(4-chlorophenyl)phosphinic Acid (3c). White amorphous solid (27 mg, 94%):17b 1H NMR (400
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5
6
31
MHz, CDCl3) δ 8.76 (s, 1H), 7.58 (t, J = 9.0 Hz, 4H), 7.31 (d, J = 8.0 Hz, 4H); P NMR (162 MHz,
CDCl3) δ 28.87; 13C NMR (100 MHz, CDCl3) δ 138.8, 132.6 (d, J = 10.9 Hz), 130.7 (d, J = 143.0 Hz),
128.8 (d, J = 13.6 Hz).
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Bis(4-fluorophenyl)phosphinic Acid (3d). White amorphous solid (23 mg, 90%): H NMR (400
31
MHz, CDCl3) δ 9.71 (s, 1H), 7.72−7.64 (m, 4H), 7.06−7.00 (m, 4H); P NMR (162 MHz, CDCl3) δ
29.38; 19F NMR (376 MHz, CDCl3) δ ꢀ106.48; 13C NMR (100 MHz, CDCl3) δ 165.1 (d, J = 252.0 Hz),
133.8 (dd, J = 11.4, 9.1 Hz), 128.6 (d, J = 144.0 Hz), 115.7 (dd, J = 21.4, 14.4 Hz); HRMS (ESIꢀTOF)
m/z: [M + 2Na ꢀ H]+ Calcd for C12H8F2O2PNa2 299.0020; Found 299.0025.
Di-m-tolylphosphinic Acid (3e). White amorphous solid (20 mg, 81%): 1H NMR (400 MHz, CDCl3)
δ 8.82 (s, 1H), 7.57−7.47 (m, 4H), 7.29−7.20(m, 4H), 2.29 (s, 6H); 31P NMR (162 MHz, CDCl3) δ 33.58;
13C NMR (100 MHz, CDCl3) δ 138.0 (d, J = 13.3 Hz), 132.6 (d, J = 2.5 Hz), 132.6 (d, J = 139.0 Hz),
131.6 (d, J = 10.5 Hz), 128.4 (d, J = 10.6 Hz), 128.2 (d, J = 14.1 Hz), 21.3; HRMS (ESIꢀTOF) m/z: [M
+ 2Na ꢀ H]+ Calcd for C14H14O2PNa2 291.0521; Found 291.0532.
Bis(3-methoxyphenyl)phosphinic Acid (3f). White amorphous solid (9 mg, 32%):20 1H NMR (400
MHz, d6ꢀDMSO) δ 7.44−7.35 (m, 2H), 7.31−7.20 (m, 4H), 7.09 (d, J = 8.0 Hz, 2H), 5.36 (s, 1H), 3.77
(s, 6H); 31P NMR (162 MHz, d6ꢀDMSO) δ 23.03; 13C NMR (100 MHz, d6ꢀDMSO) δ 159.4 (d, J = 15.8
Hz), 136.8 (d, J = 133.0 Hz), 130.3 (d, J = 14.7 Hz), 123.6 (d, J = 9.6 Hz), 117.5 (d, J = 2.5 Hz), 116.5
(d, J = 11.0 Hz), 55.7.
Bis(3,5-dimethylphenyl)phosphinic Acid (3g). White amorphous solid (24 mg, 87%):21 1H NMR
31
(400 MHz, CDCl3) δ 8.27 (s, 1H), 7.34 (d, J = 12.0 Hz, 4H), 7.06 (s, 2H), 2.27 (s, 12H); P NMR (162
MHz, CDCl3) δ 34.88; 13C NMR (100 MHz, CDCl3) δ 137.8 (d, J = 14.0 Hz), 133.5, 132.6 (d, J = 137.0
Hz), 128.7 (d, J = 10.0 Hz), 21.2.
1
Di(naphthalen-1-yl)phosphinic Acid (3h). White amorphous solid (25 mg, 78%): H NMR
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(400 MHz, CDCl3) δ 8.51 (d, J = 8.5 Hz, 2H), 8.16 (dd, J = 15.9, 6.9 Hz, 2H), 7.93 (d, J = 7.9 Hz, 2H),
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13
7.81 (d, J = 7.9 Hz, 2H), 7.45−7.28 (m, 6H), 6.32 (s, 1H); P NMR (162 MHz, CDCl3) δ 36.84; C
NMR (100 MHz, CDCl3) δ 133.6 (d, J = 10.9 Hz), 133.4 (d, J = 10.3 Hz), 133.3 (d, J = 2.9 Hz), 132.7
(d, J = 11.0 Hz), 129.0 (d, J = 136.0 Hz), 128.7, 127.1, 126.6 (d, J = 5.0 Hz), 126.1, 124.5 (d, J = 15.1
Hz); HRMS (ESIꢀTOF) m/z: [M + 2Na ꢀ H]+ Calcd for C20H14O2PNa2 363.0521; Found 363.0520.
Dibenzylphosphinic Acid (3i). White amorphous solid (16 mg, 65%):22 1H NMR (400 MHz, CDCl3)
δ 7.30−7.15 (m, 10H), 4.74 (s, 1H), 2.86 (d, J = 16.0 Hz, 4H); 31P NMR (162 MHz, CDCl3) δ 50.85; 13C
NMR (100 MHz, CDCl3) δ 131.4 (d, J = 7.3 Hz), 130.0 (d, J = 5.2 Hz), 128.5, 126.8, 36.0 (d, J = 88.0
Hz).
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Methyl Diphenylphosphinate (3j). Colorless oil (22 mg, 95%):23 1H NMR (400 MHz, CDCl3) δ
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7.84−7.77 (m, 4H), 7.55−7.49 (m, 2H), 7.48−7.41 (m, 4H), 3.76 (d, J = 11.1 Hz, 3H); P NMR (162
13
MHz, CDCl3) δ 33.26; C NMR (100 MHz, CDCl3) δ 132.2 (d, J = 2.8 Hz), 131.7 (d, J = 10.1 Hz),
131.1 (d, J = 136.0 Hz), 128.6 (d, J = 13.1 Hz), 51.5 (d, J = 6.0 Hz).
Ethyl Diphenylphosphinate (3k). Colorless oil (23 mg, 93%):24 1H NMR (400 MHz, CDCl3) δ
7.84−7.77 (m, 4H), 7.53−7.47 (m, 2H), 7.46−7.40 (m, 4H), 4.14−4.05 (m, 2H), 1.36 (t, J = 7.1 Hz, 3H);
31P NMR (162 MHz, CDCl3) δ 31.35; 13C NMR (100 MHz, CDCl3) δ 132.1 (d, J = 2.8 Hz), 131.7 (d, J
= 136 Hz), 131.6 (d, J = 10.1 Hz), 128.5 (d, J = 13.1 Hz), 61.1 (d, J = 5.9 Hz), 16.5 (d, J = 6.7 Hz).
Isopropyl Diphenylphosphinate (3l). White amorphous solid (7 mg, 27%):23 1H NMR (400 MHz,
CDCl3) δ 7.85−7.77 (m, 4H), 7.53−7.46 (m, 2H), 7.46−7.39 (m, 4H), 4.73−4.60 (m, 1H), 1.34 (d, J =
6.1 Hz, 6H); 31P NMR (162 MHz, CDCl3) δ 29.80; 13C NMR (100 MHz, CDCl3) δ 132.4 (d, J = 136.0
Hz), 131.9 (d, J = 2.7 Hz), 131.6 (d, J = 10.1 Hz), 128.4 (d, J = 13.1 Hz), 70.2 (d, J = 6.0 Hz), 24.3 (d, J
= 4.2 Hz).
Methyl Bis(4-chlorophenyl)phosphinate (3p). Colorless oil (27 mg, 90%):17b 1H NMR (400 MHz,
CDCl3) δ 7.76−7.68 (m, 4H), 7.47−7.40 (m, 4H), 3.76 (d, J = 11.2 Hz, 3H); 31P NMR (162 MHz, CDCl3)
δ 31.23; 13C NMR (100 MHz, CDCl3) δ 139.1 (d, J = 3.5 Hz), 133.0 (d, J = 11.0 Hz), 129.2 (d, J =
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139.0 Hz), 129.1 (d, J = 13.8 Hz), 51.7 (d, J = 6.0 Hz).
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Ethyl Bis(4-chlorophenyl)phosphinate (3q). Colorless oil (27 mg, 86%): H NMR (400 MHz,
CDCl3) δ 7.76−7.67 (m, 4H), 7.46−7.39 (m, 4H), 4.15−4.05 (m, 2H), 1.36 (t, J = 7.0 Hz, 3H); 31P NMR
(162 MHz, CDCl3) δ 29.31; 13C NMR (100 MHz, CDCl3) δ 139.0 (d, J = 3.6 Hz), 133.0 (d, J = 11.0 Hz),
129.9 (d, J = 139.0 Hz), 129.0 (d, J = 13.8 Hz), 61.5 (d, J = 5.9 Hz), 16.5 (d, J = 6.5 Hz); HRMS (ESIꢀ
TOF) m/z: [M + H]+ Calcd for C14H14Cl2O2P 315.0103; Found 315.0105.
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Methyl Bis(3-methoxyphenyl)phosphinate (3r). Colorless oil (18 mg, 62%):20 1H NMR (400 MHz,
CDCl3) δ 7.39−7.31 (m, 6H), 7.08−7.02 (m, 2H), 3.82 (s, 6H), 3.77 (d, J = 11.2 Hz, 3H); 31P NMR (162
MHz, CDCl3) δ 33.15; 13C NMR (100 MHz, CDCl3) δ 159.6 (d, J = 16.5 Hz), 132.3 (d, J = 135.0 Hz),
129.8 (d, J = 15.5 Hz), 123.8 (d, J = 9.8 Hz), 118.5 (d, J = 2.8 Hz), 116.4 (d, J = 11.3 Hz), 55.4, 51.6 (d,
J = 6.1 Hz).
Methyl Bis(3,5-dimethylphenyl)phosphinate (3s). Colorless oil (24 mg, 83%): 1H NMR (400 MHz,
31
CDCl3) 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); P NMR
(162 MHz, CDCl3) δ 34.45; 13C NMR (100 MHz, CDCl3) δ 138.2 (d, J = 13.8 Hz), 133.9 (d, J = 2.9 Hz),
130.9 (d, J = 135.0 Hz), 129.2 (d, J = 10.1 Hz), 51.4 (d, J = 6.0 Hz), 21.2; HRMS (ESIꢀTOF) m/z: [M +
H]+ Calcd for C17H22O2P 289.1352; Found 289.1356.
Ethyl Bis(3,5-dimethylphenyl)phosphinate (3t). Colorless oil (24 mg, 79%):25 1H NMR (400 MHz,
CDCl3) δ 7.42 (d, J = 12.5 Hz, 4H), 7.13 (s, 2H), 4.13−4.03 (m, 2H), 2.33 (s, 12H), 1.37 (t, J = 7.0 Hz,
3H); 31P NMR (162 MHz, CDCl3) δ 32.62; 13C NMR (100 MHz, CDCl3) δ 138.1 (d, J = 13.7 Hz), 133.7
(d, J = 2.8 Hz), 131.6 (d, J = 135.0 Hz), 129.2 (d, J = 10.1 Hz), 60.9 (d, J = 5.8 Hz), 21.2, 16.5 (d, J =
6.5 Hz).
Supporting Information
Copies of 1H, 13C, 19F and 31P NMR spectra for compounds 2 and 3. This material is available free of
charge via the Internet at http://pubs.acs.org.
Corresponding Author
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*Eꢀmail: qianchen@gdut.edu.cn.
Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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This work was supported by the National Natural Science Foundation of China (21242002), the
Science and Technology Planning Project of Guangdong Province (2015A020211026), and 100 Young
Talents Programme of Guangdong University of Technology (220413506).
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