Selective C-P(O) Bond Cleavage of Organophosphine Oxides by Sodium

Article abstract of DOI:10.1021/acs.joc.0c01642

Sodium exhibits better efficacy and selectivity than Li and K for converting Ph3P(O) to Ph2P(OM). The destiny of PhNa co-generated is disclosed. A series of alkyl halides R4X and aryl halides ArX all react with Ph2P(ONa) to produce the corresponding phosphine oxides in good to excellent yields.

Full text of DOI:10.1021/acs.joc.0c01642

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Selective C−P(O) Bond Cleavage of Organophosphine Oxides by
Sodium
Jian-Qiu Zhang, Eiichi Ikawa, Hiroyoshi Fujino, Yuki Naganawa, Yumiko Nakajima, and Li-Biao Han*
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Supporting Information
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ABSTRACT: Sodium exhibits better efficacy and selectivity than Li and K for
converting Ph3P(O) to Ph2P(OM). The destiny of PhNa co-generated is
disclosed. A series of alkyl halides R4X and aryl halides ArX all react with Ph2P(ONa) to produce the corresponding phosphine
oxides in good to excellent yields.
riorganylphosphine oxides R3P(O) are useful chemicals as
conditions, the reaction of Ph3P(O) with Li produced 2, 5, 4,
and 6 in 24%, 34%, 19%, and 18% yields, respectively. The
dibenzophosphole oxide 3 observed with sodium could not be
detected. Instead, two new phosphorus compounds 524 and 6
via 5′(Li) and 6′(Li), respectively, that were not observed for
sodium, were generated. The new intermediate 5′(Li) should
arise via the reaction of 2′(Li) with PhLi, and 6′(Li) was from
the reduction of 2′(Li) by lithium. On the other hand, K gave
five compounds 2, 3, 4, 7, and 8. Both 7 and 8 were new
compounds that were not observed with Li and Na, showing that
K was more reactive than Na and Li, and even two P−Ph bonds
of Ph3P(O) could be cleft by K! A reaction as shown in Scheme
2C-2 was assumed to take place for the formation of 7 (vide
infra).13 Therefore, it is concluded that, as to the selective C−P
bond cleavage of Ph3P(O) to generate Ph2P(OM), Na is better
than Li and K.14
T
extractants1,2 and flame retardants.3 They also have
applications in organic synthesis.4,5 However, methods for
their preparation are immature.6
A large amount of Ph3P(O) is produced, as byproduct, from
the chemical industry through the Witting reactions, etc.7−9
Because Ph3P(O) is rather chemically stable,10 its utilities are
limited.11 Recently, we briefly disclosed that Ph3P(O) could be
readily converted to Ph2P(ONa) by using sodium (sodium
finely dispersed in paraffin oil with μm-scale sizes, hereafter
abbreviated as SD).12 Herein, we report the details of the
reaction. As shown in Scheme 1, in addition to Ph3P(O), the
Scheme 1. Easy Preparation of Phosphine Oxides via the
Ready Cleavage of C−P and O−P Bonds by SD
As shown in Scheme 2A, 1 equiv of PhNa was co-generated from
the reaction of Ph3P(O) with SD. Although it is known that,
unlike PhLi generated using lithium (Scheme 2B) which is stable
in THF, PhNa decomposes quickly.13 However, details about
the decomposition of PhNa were not clear.13c To clarify this
decomposition, PhNa was generated separately from PhCl and
SD in THF, and then was quenched with n-C8H17Br and
PhMe2SiCl, respectively (Scheme 3a). Although the reactions
with n-C8H17Br were omittable,15 a silylvinyl ether 9 was
detected, indicating the formation of vinylate 9′ from the
reaction! However, the exact yield of 9′ was hard to determine
due to the easy decomposition of 9 in water. Fortunately, this
intermediate could be trapped by the in situ generated Ph2P(O)
H (Scheme 3b). Thus, 80% yield of 10, formed by the addition
of Ph2P(O)H to acetaldehyde,16 was obtained which indicated
method can be applied to other phosphine oxides 1A,
phosphinates 1B, and phosphonates 1C, to produce the
corresponding phosphine oxides in high yields.
It has been briefly disclosed that lithium also reacted with
Ph3P(O) to give Ph2P(OLi).12 Therefore, we decided to clarify
the difference in reactivity of Li, Na, and K. Under an argon
atmosphere, 2.5 equiv of an alkali metal cut into small pieces was
added to Ph3P(O) dissolved in THF at room temperature
(Scheme 2). All the three alkali metals could react quickly with
Ph3P(O) as the initially colorless solution instantly changed to
brown. The mixture was stirred at room temperature overnight,
and then quenched using n-butyl bromide and analyzed by GC-
MS and 31P NMR spectroscopies (see Supporting Information
for details). As reported before, the reaction of Ph3P(O) with Na
after quenching with n-BuBr produced n-butyldiphenyl
phosphine oxide Ph2P(O)n-Bu 2, 5-butyldibenzophosphole 5-
oxide 3, and 5-butyldibenzophosphole 4, via the reactions of the
corresponding sodium salts of 2′(Na), 3′(Na), and 4′(Na), in
69%, 26%, and 5% yields, respectively.12 Under similar
Received: July 10, 2020
https://dx.doi.org/10.1021/acs.joc.0c01642
© XXXX American Chemical Society
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a
Scheme 2. Reactions of Ph3P(O) with Alkali Metals
a
Reaction conditions: under Ar, Ph3P(O) (1.0 mmol), alkali metal (2.5 mmol), THF (5.0 mL), 25 °C, overnight. Then n-BuBr (2.0 mmol), 25 °C,
0.5 h. Yields refer to 31P NMR yields based on Ph3P(O) used.
a
Scheme 3. Decomposition of PhNa by THF
a
Conditions: (a) PhCl (1.0 mmol), SD (2.0 mmol), THF (5.0 mL), 25 °C, 1 h. (b) Electrophiles (1.2 mmol), 25 °C, 0.5 h. (c) Ph3P(O) (1.0
mmol), SD (2.5 mmol), THF (5 mL), 25 °C, 10 min.
that 9′ was the sodium alkoxide predominantly generated from
the reaction of PhNa with THF (Scheme 3c).13
Therefore, 9′ was the main co-product in the solution of
Ph2P(ONa) generated from Ph3P(O) and SD. The fortunate
thing is that, unlike PhLi (Scheme 3b), the presence of 9′ affects
little the following reactions of Ph2P(ONa) with an electro-
phile17 such as RX because of its relatively low reactivity and the
relatively high reactivity of Ph2P(ONa); i.e., in most cases,
Ph2P(ONa) generated from Ph3P(O) and SD can be used as it
in the presence of 9′.12
B
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Note
a
Scheme 4. Selectivity of the C−P Bond Cleavage
a
Conditions: Ph2P(O)R (0.3 mmol), THF (2.0 mL), SD (0.3 mmol), 25 °C, 1 h. Then an excess amount of n-BuBr, 25 °C, 0.5 h. Yields were
b
determined by GC. The ratio of P−R bond and P−Ph bond cleavage was determined by GC. The data in parentheses were for reactions
conducted in 1,4-dioxane.
As shown in Scheme 4, the C−P bond cleavages of
unsymmetrical diphenylalkylphosphine oxides were studied.
All these phosphine oxides reacted similarly to Ph3P(O) to
generate the corresponding R2P(ONa). As exemplified by the
reaction of Ph2P(O)Me 1a, to the phosphine oxide in THF was
added 1 equiv of SD at room temperature to generate an orange
solution. The mixture was stirred for 1 h and then quenched with
an excess amount of n-BuBr. Compound 1a-1 was obtained in
36% GC yield, and compound 1a-2 could not be detected at all.
As expected, compound 1a-3 via the reactions of PhNa and 1a
was also obtained in 43% yield. By conducting similar reactions,
the selectivity on the C−P bond cleavage of diphenyl(alkyl)-
phosphine oxides Ph2P(O)R (P−Ph vs P−R) was determined.
Thus, while cleavage on the P−Ph bond took place exclusively
with Me, n-Bu, and i-Pr groups, interestingly, for Ph2P(O)t-Bu,
the selectivity of P−Ph vs P−t-Bu is 80/20, and for Ph2P(O)Bn,
the selectivity even became to 47/53, showing that it is equally
easy to break the P−Bn bond and the P−Ph bond.
Table 1. Conversion of Phosphine Oxides to Other
Organophosphorus by SD
a
In order to make the present SD-mediated C−P bond cleavage a
general method for the synthesis of organophosphine oxides, we
first have to fix the abstraction problem of the α-protons at R of
Ph2P(O)R by PhNa as exemplified by Ph2P(O)Me (Scheme 4).
Since the generation of the side product 1a-3′(Na) by PhNa
(Scheme 4) is a competition reaction with the generation of the
aimed product 1a-1′(Na) by Na, we realized that, by using an
excess amount of Na, this side reaction could be suppressed (see
Supplementary Table 1).
As shown in Table 1, the reactions of representative
phosphine oxides and related were investigated. Highly selective
Ph−P bond cleavage of Ph2P(O)R took place efficiently, where
R can be methyl (run 1), primary (runs 2 and 3), secondary
(runs 4 and 5), and tertiary (run 6) alkyl groups, to produce the
corresponding PhRP(ONa) that was trapped by an alkyl
bromide to give the corresponding new phosphine oxides in
good to excellent yields. However, Ph2P(O)CH2Ph gave
complicated results under similar conditions (run 7) due to
the bad selectivity of the C−P bond cleavages (Scheme 4) and
the easier deprotonation of the benzyl proton of Ph2P(O)-
CH2Ph by a base. After carrying out an extensive study on the
optimization of the reaction conditions, we found that, by
conducting the reaction in 1,4-dioxane at 100 °C, Ph2P(O)n-Bu
1g-1, assumed from the P−Bn bond cleavage, was obtained in
53% yield.18 Dibutylphenylphosphine oxide could be also used
as the substrate, and the Ph−P bond was selectively cleft (run 8).
However, trioctylphosphine oxide did not react even at a higher
temperature (run 9).
a
Reaction conditions: 1 (0.3 mmol), SD (1.0 mmol), 1,4-dioxane (2.0
mL), 60 °C, 24 h. Then n-BuBr (0.4 mmol), 25 °C, 0.5 h. Isolated
b
c
yield. n-OctBr (0.4 mmol) was used. SD (1.8 mmol), n-BuBr (0.8
d
e
mmol). Yield was determined by 31P NMR based on 1m used. SD
(2.4 mmol), n-BuBr (1.0 mmol).
In addition to tertiary phosphine oxides, the reactions of
phosphinic (runs 10 and 11), phosphonic (runs 12 and 13), and
phosphoric (run 14) esters were also examined. Only the
products from the cleavage of the P−O bonds were obtained.
Thus, diphenylphosphinates like Ph2P(O)Ot-Bu and Ph2P(O)-
OPh generated Ph2PONa in high yields (runs 10 and 11).
Surprisingly, with PhP(O)(OPh)2, the two P−O bonds could be
readily broken and the product PhP(O)n-Bu2 assumed via the
reaction of PhP(Na)ONa and n-BuBr was obtained in good
yield (run 12). However, under similar conditions, PhP(O)-
C
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(OMe)2 gave a complex mixture and only 31% PhP(O)n-Bu2
was obtained (run 13). Although (PhO)3P(O) also reacted with
SD rapidly, the result was complicated and only a trace amount
of n-Bu3P(O) could be detected (run 14).
Table 3. Palladium-Catalyzed Cross-Coupling Reactions of
Ph2PONa and Aryl Halides
a
As outlined in Table 2, n-BuCl and n-BuI could also be used as
electrophiles for trapping Ph2P(ONa) to generate the
a
Table 2. Scope of Alkyl Halides
a
Reaction conditions: Ph3P(O) (0.2 mmol), SD (0.5 mmol), 1,4-
dioxane (1.0 mL), 25 °C, 10 min. Then Pd(Ph3P)2Cl2 (5 mol %) and
ArX (0.2 mmol) were sequentially added, 100 °C, 24 h. Isolated yield.
b
c
Pd(OAc)2/dppf (5 mol %) was used. Ph3P(O) (1.0 mmol), SD
(2.5 mmol), 1,4-dioxane (5.0 mL), 25 °C, 10 min. And then
Pd(Ph3P)2Cl2 (2 mol %), 2-chloronaphthalene (1.0 mmol), 120 °C,
30 h.
Scheme 5. Mechanism of P−R bond Cleavage
a
Reaction conditions: Ph3P(O) (0.2 mmol), SD (0.5 mmol), 1,4-
dioxane (1.0 mL), 25 °C, 10 min. Then R4X (0.3 mmol), 25 °C, 0.5 h.
Isolated yield. 60 °C, overnight. 15-Crown-5 ether (0.2 mmol) was
added at step 2. 100 °C, overnight.
b
c
d
can react with a variety of organic halides to afford the
corresponding new phosphine oxides in good yields.
corresponding product in high yields, though heating is
necessary for n-BuCl. Electrophiles were readily extended to
other primary alkyl bromides with functional groups such as Cl
and Br (2-1b−d) as well as secondary alkyl chlorides (2-1e and
2-1f). Unfortunately, the reaction of Ph2P(ONa) with tertiary
alkyl halides such as t-butyl and admantyl halides gave complex
mixtures and no desired products could be obtained (2-1g and
2-1h).
Ph2P(ONa) can also be used in the cross-coupling reactions
with aryl halides ArX to produce diphenyl(aryl)phosphine
oxides. Transition-metal-catalyzed couplings of Ph2P(O)H with
the aryl bromides or aryl iodides were well-studied;19 however,
reactions with the less reactive aryl chlorides, especially the
electron-rich aryl chlorides, were limited.20 By using palladium
as the catalyst, we could successfully couple Ph2PONa with p-
tolyl chloride to produce the coupling product in high yields (see
Supplementary Table 2).21 This Pd-catalyzed coupling reaction
can be applied to a variety of other aryl chlorides (Table 3). For
example, the electron-rich aryl chlorides including those with
tert-butyl, methoxyl, and tert-butoxyl groups on the benzene ring
were suitable substrates, affording the corresponding coupling
products in high yields (2-2b to 2-d). 2-Pyridyl chloride was also
tolerated in this catalyzed reaction and formed the products in
moderate yield (2-2f). The catalyst loading could be reduced to
2 mol % without reducing the reaction’s efficacy, as 2-
chloronaphthalene was readily phosphorylated to 2-2g in 90%
yield.
EXPERIMENTAL SECTION
■
General Information. The reactions were carried out in oven-dried
Schlenk tubes under an argon atmosphere. The sodium we used was
dispersed in paraffin oil with an average particle size smaller than 10 μm
and a concentration of ∼10.0 mol/L. MS (ESI) data were obtained on a
SHIMADZU GC-MS 2010 plus. The High-resolution ESI mass spectra
were obtained on a Bruker micrOTOF II. Column chromatography was
performed using Silica Gel 60 N (TCI, spherical, neutral). HPLC
(recycle GPC) isolation was performed using a JAPAN ANALYTICAL
INDUSTRY LC-908, equipped with two preparative columns (20 mm
× 600 mm; JAIGEL-1H and JAIGEL-2H). CHCl3 (flow rate: 4.0 mL/
1
min) was used as eluent. H, 13C, and 31P NMR were recorded on a
JEOL JNM-ECS400 (400 MHz for 1H NMR, 100 MHz for 13C NMR,
and 162 MHz for 31P NMR spectroscopy). Chemical shifts for 1H NMR
are referred to internal Me4Si (0 ppm) and reported as follows:
chemical shift (δ ppm), multiplicity, coupling constant (Hz), and
integration. Chemical shifts for 31P NMR were relative to H3PO4 (85%
solution in D2O, 0 ppm). The melting points were obtained on an SRS
OptiMelt.
Typical Experimental Procedure for the Synthesis of
Phosphine Oxide 1a-1 from 1a by SD. Under an argon atmosphere,
to a stirring solution of diphenyl(methyl)phosphine oxide 1a (0.3
mmol, 1 equiv, 64.8 mg) in 1,4-dioxane (2.0 mL) was added SD (1.0
mmol, 3.3 equiv, 0.1 mL) via a syringe. The mixture was then stirred at
60 °C for 24 h. After removal of the excessive Na by filtration, n-BuBr
(0.4 mmol, 1.33 equiv, 43 μL) was added, and further stirring the
mixture was continued for 0.5 h. After that, the resulting mixture was
filtered and concentrated under vacuum. Next, the obtained residue was
directly eluted with hexane via a silica gel column and then eluted with
MeOH to give the crude product, which was then diluted in CHCl3 and
purified by GPC to afford pure product 1a-1 (52.3 mg, 0.267 mmol,
89% yield).
Although the detailed reaction path is not clear, we propose a
single electron transfer (SET) mechanism for the cleavage of the
P−R bond (Scheme 5) that might account for the results
obtained above.22,23
In summary, Na shows the best efficiency and selectivity for
cleaving the C−Ph bond of Ph3P(O). A variety of phosphine
oxides reacted with SD, via selective P−C or P−O bond
cleavages, and efficiently produced P-ONa intermediates that
Experimental Procedure for 2 mmol Scale Synthesis of
Phosphine Oxide 1b-1 from 1b by SD. Under an argon
atmosphere, to a stirring solution of diphenyl(butyl)phosphine oxide
1b (2.0 mmol, 1 equiv, 516.2 mg) in 1,4-dioxane (10.0 mL) was added
D
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SD (8.0 mmol, 4 equiv, 0.8 mL) via a syringe. The mixture was then
stirred at 60 °C for 48 h. After removal of the excessive Na by filtration,
n-BuBr (3.0 mmol, 1.5 equiv, 161 μL) was added, and further stirring
the mixture for 2 h. After that, the resulting mixture was filtered and
concentrated under vacuum. Next, the residue was then purified by
flash column chromatography on silica gel with hexane/ethyl acetate
(1:1) to give the desired product 1b-1 (409.6 mg, 1.72 mmol, 86%
yield).
Typical Experimental Procedure for Pd-Catalyzed Coupling
Reaction of Ph2P(ONa) with p-MeC6H4Cl Generating Diphenyl-
(p-tolyl)phosphine Oxide 2-2a. Under an argon atmosphere, to a
stirring solution of triphenylphosphine oxide (0.2 mmol, 1 equiv, 55.6
mg) in 1,4-dioxane (1.0 mL) was added SD (0.5 mmol, 2.5 equiv, 50.0
μL) via a syringe. The mixture was then stirred at 25 °C for 10 min.
After removal of the excessive Na by filtration, Pd(Ph3P)Cl2 (5 mol %,
7.0 mg) and p-MeC6H4Cl (0.2 mmol, 1.0 equiv, 24.0 μL) were
sequentially added, and further stirring the mixture at 100 °C for 24 h.
After that, the resulting mixture was filtered and concentrated under
vacuum. Next, the obtained residue was directly eluted with hexane via
a silica gel column and then eluted with MeOH to give the crude
product, which was then diluted in CHCl3 and purified by GPC to
afford pure product 2-2a (49.7 mg, 0.17 mmol, 85% yield).
Comparison Experimental Procedure for the Treatments of
Ph3P(O) with Alkali Metals (Na, Li, K, Mg). Under an argon
atmosphere, to a solution of Ph3P(O) (1.0 mmol, 278.0 mg) in THF (5
mL) was added alkali (Li, Na, K) or alkaline-earth (Mg) metal (2.5
mmol) cut into tiny pieces. After stirring the mixture at room
temperature for 24 h, excessive n-BuBr was added, and then the
resulting mixture was analyzed by 31P NMR, GC, and GC-MS.
Synthesis of Compound 5 by Literature Method.24 Under an
argon atmosphere, s-BuLi (2.0 mmol, 1.04 mol/L solution in hexane,
2.0 mL) was added in dropwise to the stirred solution of Ph2P(O)n-Bu
(1.0 mmol, 258.0 mg) in THF (4.0 mL) at −78 °C. After stirring for 30
min, the reaction mixture was warmed to 0 °C, n-BuBr (2.0 mmol, 215
μL) was added, and stirring the mixture for another 30 min. After that,
the mixture was quenched with saturated NH4Cl aqueous solution (5
mL) at 0 °C and extracted with CH2Cl2 (5 mL × 3); then the combined
organic layer was dried over anhydrous Na2SO4, filtered, and
concentrated under vacuum. The residue was diluted in CHCl3 and
purified by GPC to afford pure product 5 (238 mg, 0.76 mmol, 76%
yield).
Synthesis of Compound 10. Under an argon atmosphere, to a
stirring solution of Ph3P(O) (1.0 mmol, 1 equiv) in THF (5.0 mL) was
added SD (3.0 mmol, 3 equiv, 0.3 mL) via a syringe. After stirring the
mixture at room temperature for 0.5 h, saturated NH4Cl aqueous
solution (5.0 mL) was added and then extracted with EtOAc (5 mL ×
3); the combined organic layer was dried over anhydrous Na2SO4,
filtered, and concentrated under vacuum. The residue was eluted with
hexane via a silica gel column and then eluted with MeOH to give the
crude product, which was then diluted in CHCl3 and purified by GPC
to afford pure product 10 (196 mg, 0.80 mmol, 80% yield).
MS (ESI) m/z: ([M]+) Calcd for C14H23OP 238, Found 238. This
compound is known.25b
Dioctyl(phenyl)phosphine Oxide (1c-1). White solid: 100.8 mg,
96% yield. 1H NMR (400 MHz, CDCl3): δ 7.67−7.62 (m, 2H), 7.49−
7.41 (m, 3H), 1.97−1.76 (m, 5H), 1.63−1.50 (m, 2H), 1.44−1.17 (m,
21H), 0.83−0.79 (m, 6H). 13C {1H} NMR (100 MHz, CDCl3): δ
132.5 (d, Jp‑c = 91.9 Hz), 131.5 (d, Jp‑c = 1.8 Hz), 130.5 (d, Jp‑c = 8.7
Hz), 128.6 (d, Jp‑c = 11.2 Hz), 31.8, 31.1, 30.9, 29.9 (d, Jp‑c = 67.9 Hz),
29.1, 22.6, 21.5 (d, Jp‑c = 3.8 Hz), 14.1. 31P NMR (162 MHz, CDCl3): δ
42.0. MS (ESI) m/z: ([M]+) Calcd for C22H39OP 350, found 350. This
compound is known.25c,d
Butyl(isopropyl)(phenyl)phosphine Oxide (1d-1). Colorless oil:
1
61.8 mg, 92% yield. H NMR (400 MHz, CDCl3): δ 7.67−7.61 (m,
2H), 7.48−7.40 (m, 3H), 2.05−1.95 (m, 2H), 1.83−1.80 (m, 1H),
1.61−1.54 (m, 1H), 1.37−1.25 (m, 3H), 1.16 (dd, 3H, J1 = 15.6 Hz, J2 =
6.8 Hz), 0.88 (dd, 3H, J1 = 16.0 Hz, J2 = 7.2 Hz), 0.81 (t, 3H, J = 7.2 Hz).
13C {1H} NMR (100 MHz, CDCl3): δ 131.9, 131.4 (d, Jp‑c = 2.3 Hz),
131.0 (d, Jp‑c = 8.2 Hz), 128.5 (d, Jp‑c = 10.7 Hz), 28.6 (d, Jp‑c = 68.9
Hz), 26.4 (d, Jp‑c = 66.1 Hz), 24.2 (d, Jp‑c = 13.7 Hz), 23.5 (d, Jp‑c = 4.2
Hz), 15.8 (d, Jp‑c = 1.1 Hz), 15.2 (d, Jp‑c = 2.4 Hz), 13.6. 31P NMR (162
MHz, CDCl3): δ 46.4. HRMS (ESI-TOF): m/z: ([M + Na]+) Calcd for
C13H21OPNa 247.1228, Found 247.1224.
sec-Butyl(butyl)(phenyl)phosphine Oxide (1e-1). White solid: 70.6
1
mg, 99% yield. H NMR (400 MHz, CDCl3): δ 7.63−7.59 (m, 2H),
7.44−7.39 (m, 3H), 2.04−1.89 (m, 1H), 1.82−1.72 (m, 2H), 1.55−
1.54 (brs, 1H), 1.37−1.18 (m, 4H), 1.13 (dd, 2H, J1 = 16.0 Hz, J2 = 7.2
Hz), 0.98−0.70 (m, 8H). 13C {1H} NMR (100 MHz, CDCl3): δ 131.3,
131.0 (d, Jp‑c = 5.3 Hz), 130.9 (d, Jp‑c = 5.6 Hz), 128.5 (dd, J1 = 10.5 Hz,
J2 = 2.5 Hz), 35.5 (dd, J1 = 68.2 Hz, J2 = 10.1 Hz), 26.6 (d, Jp‑c = 65.6
Hz), 24.2 (d, Jp‑c = 13.8 Hz), 23.4, 22.3 (d, Jp‑c = 52.0 Hz), 13.6, 8.4 (dd,
J1 = 12.8 Hz, J2 = 4.4 Hz), 11.8 (d, Jp‑c = 52.7 Hz). 31P NMR (162 MHz,
CDCl3): δ 46.0. MS (ESI) m/z: ([M]+) Calcd for C14H23OP 238,
found 238. This compound is known.25e
tert-Butyl(butyl)(phenyl)phosphine Oxide (1f-1). White solid: 64.3
1
mg, 90% yield. H NMR (400 MHz, CDCl3): δ 7.67−7.60 (m, 2H),
7.48−7.40 (m, 3H), 2.00−1.90 (m, 2H), 1.67−1.54 (m, 1H), 1.42−
1.21 (m, 3H), 1.07 (d, 9H, J = 14.0 Hz), 0.82 (t, 3H, J = 7.6 Hz). 13C
{1H} NMR (100 MHz, CDCl3): δ 131.9 (d, Jp‑c = 7.7 Hz), 131.4 (d, Jp‑c
= 2.5 Hz), 130.9 (d, Jp‑c = 9.3 Hz), 130.2 (d, Jp‑c = 85.6 Hz), 128.7 (d,
Jp‑c = 11.4 Hz), 128.3 (d, Jp‑c = 10.4 Hz), 32.7 (d, Jp‑c = 68.1 Hz),
24.6brs, 24. (d, Jp‑c = 13.9 Hz), 23.6 (d, Jp‑c = 4.2 Hz), 22.7 (d, Jp‑c = 64.4
Hz), 13.7. 31P NMR (162 MHz, CDCl3): δ 50.3. MS (ESI) m/z:
([M]+) Calcd for C14H23OP 238, found 238. This compound is
known.25a
Diphenyl(butyl)phosphine Oxide (1g-1). White solid: 41.0 mg, 53%
yield. 1H NMR (400 MHz, CDCl3): δ 7.74−7.69 (m, 4H), 7.48−7.42
(m, 6H), 2.27−2.20 (m, 2H), 1.63−1.53 (m, 2H), 1.44−1.35 (m, 2H),
0.86 (t, 3H, J = 7.6 Hz). 13C {1H} NMR (100 MHz, CDCl3): δ 133.3
(d, Jp‑c = 96.9 Hz), 131.7 (d, Jp‑c = 2.1 Hz), 130.9 (d, Jp‑c = 9.2 Hz),
128.7 (d, Jp‑c = 11.4 Hz), 29.6 (d, Jp‑c = 71.8 Hz), 24.2 (d, Jp‑c = 15.1
Hz), 23.6 (d, Jp‑c = 3.7 Hz), 13.7. 31P NMR (162 MHz, CDCl3): δ 33.1.
MS (ESI) m/z: ([M]+) Calcd for C16H19OP 258, Found 258. This
compound is known.25f
Diphenyl(1-phenylpentyl)phosphine Oxide (1g-3). White solid:
44.9 mg, 43% yield. mp 205−208 °C. 1H NMR (400 MHz, CDCl3): δ
7.92−7.87 (m, 2H), 7.56−7.49 (m, 3H), 7.42−7.38 (m, 2H), 7.32−
7.28 (m, 1H), 7.22−7.13 (m, 7H), 3.41−3.35 (m, 1H), 2.18−2.06 (m,
1H), 1.92−1.82 (m, 1H), 1.25−1.09 (m, 4H), 0.73 (t, 3H, J = 7.2 Hz).
13C{1H} NMR (100 MHz, CDCl3): δ 136.1 (d, Jp‑c = 5.2 Hz), 132.8 (d,
1H and 13C NMR and 31P NMR Spectral Data of the Products.
Butyl(methyl)(phenyl)phosphine Oxide (1a-1). White solid: 52.3 mg,
89% yield. 1H NMR (400 MHz, CDCl3): δ 7.70−7.65 (m, 2H), 7.49−
7.42 (m, 3H), 2.01−1.80 (m, 2H), 1.67 (d, 3H, J = 12.4 Hz), 1.59−1.48
(m, 1H), 1.46−1.39 (m, 1H), 1.38−1.29 (m, 2H), 0.83 (t, 3H, J = 7.6
Hz). 13C {1H} NMR (100 MHz, CDCl3): δ 133.6 (d, Jp‑c = 95.3 Hz),
131.7 (d, Jp‑c = 2.1 Hz), 130.1 (d, Jp‑c = 9.0 Hz), 128.7 (d, Jp‑c = 11.3
Hz), 31.5 (d, Jp‑c = 70.1 Hz), 24.0 (d, Jp‑c = 15.1 Hz), 23.72 (d, Jp‑c = 4.0
Hz), 16.0 (d, Jp‑c = 69.4 Hz), 13.6. 31P NMR (162 MHz, CDCl3): δ
39.0. MS (ESI) m/z: ([M]+) Calcd for C11H17OP 196, Found 196. This
compound is known.25a
Dibutyl(phenyl)phosphine Oxide (1b-1). White solid: 65.7 mg, 92%
yield. 1H NMR (400 MHz, CDCl3): δ 7.59−7.64 (m, 2H), 7.49−7.43
(m, 3H), 2.00−1.77 (m, 4H), 1.64−1.53 (m, 2H), 1.44−1.28 (m, 6H),
0.84 (t, 6H, J = 7.2 Hz). 13C {1H} NMR (100 MHz, CDCl3): δ 132.6
(d, Jp‑c = 91.4 Hz), 131.5 (d, Jp‑c = 2.4 Hz), 130.5 (d, Jp‑c = 8.6 Hz),
128.7 (d, Jp‑c = 11.1 Hz), 29.7 (d, Jp‑c = 68.1 Hz), 24.2 (d, Jp‑c = 14.4
Hz), 23.6 (d, Jp‑c = 4.2 Hz), 13.6. 31P NMR (162 MHz, CDCl3): δ 41.6.
J
p‑c = 27.0 Hz), 131.4 (d, Jp‑c = 8.3 Hz), 131.2 (d, Jp‑c = 1.9 Hz), 131.1
(d, Jp‑c = 8.7 Hz), 129.9 (d, Jp‑c = 5.8 Hz), 128.7 (d, Jp‑c = 10.9 Hz),
128.0 (d, Jp‑c = 11.4 Hz), 126.9 (d, Jp‑c = 2.2 Hz), 47.0 (d, Jp‑c = 67.0
Hz), 30.0 (d, Jp‑c = 12.9 Hz), 28.8, 22.2, 13.8. 31P NMR (162 MHz,
CDCl3): δ 33.5. HRMS (ESI-TOF): m/z: ([M + Na]+) Calcd for
C23H25OPNa 371.1541, Found 371.1538.
Tributylphosphine Oxide (1h-1). White solid: 56.9 mg, 87% yield.
1H NMR (400 MHz, CDCl3): δ 1.62−1.55 (m, 6H), 1.53−1.41 (m,
6H), 1.39−1.27 (m, 6H), 0.86−0.81 (m, 9H). 13C {1H} NMR (100
MHz, CDCl3): δ 27.7 (d, Jp‑c = 64.7 Hz), 24.3 (d, Jp‑c = 14.1 Hz), 23.8
(d, Jp‑c = 3.3 Hz), 13.6. 31P NMR (162 MHz, CDCl3): δ 49.1. MS (ESI)
E
https://dx.doi.org/10.1021/acs.joc.0c01642
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
m/z: ([M]+) Calcd for C12H27OP 218, found 218. This compound is
known.25a
11.9 Hz), 21.7. 31P NMR (162 MHz, CDCl3): δ 30.1. This compound is
known.27a
(4-(tert-Butyl)phenyl)diphenylphosphine Oxide (2-2b). White
Octan-4-yldiphenylphosphine Oxide (5). Preparation by literature
method.24 White solid: 238 mg, 76% yield). mp 151−154 °C. 1H NMR
(400 MHz, CDCl3): δ 7.81−7.76 (m, 4H), 7.48−7.42 (m, 6H), 2.25−
2.16 (m, 1H), 1.73−1.59 (m, 2H), 1.56−1.39 (m, 4H), 1.25−1.13 (m,
4H), 0.80−0.75 (m, 6H); 13C {1H} NMR (100 MHz, CDCl3): δ 133.2
(dd, J1 = 93.6 Hz, J2 = 2.9 Hz), 131.4 (d, Jp‑c = 2.4 Hz), 131.0 (dd, J1 =
8.5 Hz, J2 = 1.1 Hz), 128.6 (d, Jp‑c = 11.1 Hz), 37.1 (d, Jp‑c = 70.3 Hz),
30.3 (d, Jp‑c = 9.2 Hz), 29.9, 27.3, 22.8, 21.3 (d, Jp‑c = 9.4 Hz), 14.3, 13.9;
31P NMR (162 MHz, CDCl3): δ 37.3. HRMS (ESI-TOF): m/z: ([M +
Na]+) Calcd for C20H27OPNa 337.1697, Found 337.1698.
(1-Hydroxyethyl)diphenylphosphine Oxide (10). White solid:
196.7 mg, 80% yield. 1H NMR (400 MHz, CDCl3): δ 7.88−7.83 (m,
2H), 7.78−7.73 (m, 2H), 7.50−7.38 (m, 6H), 4.88 (brs, 1H), 4.57−
4.52 (m, 1H), 1.39 (dd, 3H, J1 = 15.6 Hz, J2 = 7.2 Hz). 13C{1H} NMR
(100 MHz, CDCl3): δ 132.5 (d, Jp‑c = 8.0 Hz), 132.1 (d, Jp‑c = 8.9 Hz),
132.0 (d, Jp‑c = 3.6 Hz), 131.6 (d, Jp‑c = 8.9 Hz), 130.7 (d, Jp‑c = 8.2 Hz),
1
solid: 52.8 mg, 79% yield. H NMR (400 MHz, CDCl3): δ 7.70−
7.64 (m, 4H), 7.60−7.52 (m, 4H), 7.48−7.42 (m, 6H), 1.31 (s, 9H).
13C {1H} NMR (100 MHz, CDCl3): δ 155.5 (d, Jp‑c = 2.8 Hz), 132.9
(d, Jp‑c = 103.6 Hz), 132.2 (d, Jp‑c = 10.0 Hz), 132.1 (d, Jp‑c = 10.8 Hz),
131.9 (d, Jp‑c = 2.1 Hz), 129.2 (d, Jp‑c = 105.9 Hz), 128.5 (d, Jp‑c = 12.0
Hz), 125.6 (d, Jp‑c = 12.1 Hz), 35.1, 31.2. 31P NMR (162 MHz, CDCl3):
δ 29.6. This compound is known.27b
(4-Methoxyphenyl)diphenylphosphine Oxide (2-2c). White solid:
1
46.8 mg, 76% yield. H NMR (400 MHz, CDCl3): δ 7.66−7.60 (m,
4H), 7.58−7.52 (m, 2H), 7.51−7.46 (m, 2H), 7.43−7.38 (m, 4H),
6.94−6.91 (m, 2H), 3.79 (s, 3H). 13C {1H} NMR (100 MHz, CDCl3):
δ 162.6 (d, Jp‑c = 2.6 Hz), 134.0 (d, Jp‑c = 11.3 Hz), 133.0 (d, Jp‑c = 103.9
Hz), 132.1 (d, Jp‑c = 9.7 Hz), 131.9 (d, Jp‑c = 2.1 Hz), 128.5 (d, Jp‑c
12.2 Hz), 123.6 (d, Jp‑c = 109.8 Hz), 114.2 (d, Jp‑c = 13.1 Hz), 55.4. 31
NMR (162 MHz, CDCl3): δ 29.7. This compound is known.27a
=
P
(4-(tert-Butoxy)phenyl)diphenylphosphine Oxide (2-2d). White
129.8, 128.6 (d, Jp‑c = 10.6 Hz), 128.5 (d, Jp‑c = 10.7 Hz), 66.7 (d, Jp‑c
=
1
84.0 Hz), 17.0. 31P NMR (162 MHz, CDCl3): δ 33.6. This compound is
solid: 57.4 mg, 82% yield. mp 135−141 °C. H NMR (400 MHz,
known.25a
CDCl3): δ 7.68−7.63 (m, 4H), 7.55−7.50 (m, 4H), 7.46−7.42 (m,
4H), 7.05−7.02 (m, 2H), 1.38 (s, 9H). 13C {1H} NMR (100 MHz,
CDCl3): δ 159.3 (d, Jp‑c = 2.6 Hz), 133.4 (d, Jp‑c = 10.8 Hz), 132.3 (d,
Benzyldiphenylphosphine Oxide (2-1b). White solid: 55.5 mg, 95%
yield. 1H NMR (400 MHz, CDCl3): δ 7.70−7.65 (m, 4H), 7.50−7.39
(m, 6H), 7.16−7.08 (m, 5H), 3.64 (d, 2H, J = 13.6 Hz). 13C {1H}
J
p‑c = 20.4 Hz), 132.2 (d, Jp‑c = 9.7 Hz), 131.9 (d, Jp‑c = 2.3 Hz), 128.5
(d, Jp‑c = 12.1 Hz), 125.9 (d, Jp‑c = 108.0 Hz), 122.9 (d, Jp‑c = 13.0 Hz),
79.6, 29.0. 31P NMR (162 MHz, CDCl3): δ 29.8. HRMS (ESI-TOF):
m/z: ([M + Na]+) Calcd for C22H23NaO2P 373.1333, Found 373.1335.
4-(Diphenylphosphoryl)benzonitrile (2-2e). White solid: 29.1 mg,
48% yield. 1H NMR (400 MHz, CDCl3): δ 7.80−7.71 (m, 4H), 7.65−
7.54 (m, 6H), 7.49−7.45 (m, 4H). 13C {1H} NMR (100 MHz,
CDCl3): δ 138.6 (d, Jp‑c = 98.5 Hz), 132.7 (d, Jp‑c = 10.9 Hz), 132.6 (d,
NMR (100 MHz, CDCl3): δ 132.4 (d, Jp‑c = 98.5 Hz), 131.9 (d, Jp‑c
=
2.3 Hz), 131.3 (d, Jp‑c = 9.2 Hz), 130.2 (d, Jp‑c = 5.4 Hz), 128.6, 128.5,
128.45 (d, Jp‑c = 1.9 Hz), 126.8 (d, Jp‑c = 1.7 Hz), 38.2 (d, Jp‑c = 66.1
Hz). 31P NMR (162 MHz, CDCl3): δ 30.0. This compound is
known.26a
(4-Chlorobenzyl)diphenylphosphine Oxide (2-1c). White solid:
1
64.6 mg, 99% yield. H NMR (400 MHz, CDCl3): δ 7.70−7.65 (m,
J
p‑c = 3.1 Hz), 132.1 (d, Jp‑c = 10.5 Hz), 131.3 (d, Jp‑c = 104.9 Hz), 128.9
4H), 7.53−7.48 (m, 2H), 7.45−7.41 (m, 4H), 7.14 (d, 2H, J = 8.4 Hz),
7.04−7.01 (m, 2H), 3.59 (d, 2H, J = 13.6 Hz). 13C {1H} NMR (100
MHz, CDCl3): δ 132.9 (d, Jp‑c = 3.2 Hz), 132.1 (d, Jp‑c = 98.8 Hz), 132.0
(d, Jp‑c = 2.3 Hz), 131.5 (d, Jp‑c = 5.2 Hz), 131.2 (d, Jp‑c = 9.3 Hz), 129.8
(d, Jp‑c = 8.2 Hz), 128.7, 128.6, 37.6 (d, Jp‑c = 65.8 Hz). 31P NMR (162
MHz, CDCl3): δ 29.7. This compound is known.26b
(d, Jp‑c = 12.3 Hz), 128.6 (d, Jp‑c = 12.1 Hz), 117.9, 115.7 (d, Jp‑c = 3.1
Hz). 31P NMR (162 MHz, CDCl3): δ 28.3. This compound is
known.27c
Diphenyl(pyridin-2-yl)phosphine Oxide (2-2f). White solid: 25.2
mg, 45% yield. 1H NMR (400 MHz, CDCl3): δ 8.76 (d, 1H, J = 4.8 Hz),
8.29 (t, 1H, J = 4.8 Hz), 7.90−7.80 (m, 5H), 7.52−7.47 (m, 2H), 7.45−
7.41 (m, 4H), 7.38−7.35 (m, 1H). 13C {1H} NMR (100 MHz,
CDCl3): δ 156.5 (d, Jp‑c = 131.2 Hz), 150.2 (d, Jp‑c = 19.1 Hz), 136.3 (d,
(4-Bromobenzyl)diphenylphosphine Oxide (2-1d). White solid:
1
67.3 mg, 91% yield. H NMR (400 MHz, CDCl3): δ 7.70−7.65 (m,
4H), 7.53−7.49 (m, 2H), 7.46−7.41 (m, 4H), 7.29 (d, 2H, J = 8.4 Hz),
6.98−6.96 (m, 2H). 3.58 (d, 2H, J = 13.6 Hz). 13C {1H} NMR (100
MHz, CDCl3): δ 132.1 (d, Jp‑c = 100.7 Hz), 132.0 (d, Jp‑c = 2.3 Hz),
131.8 (d, Jp‑c = 5.3 Hz), 131.6 (d, Jp‑c = 2.0 Hz), 131.2 (d, Jp‑c = 9.0 Hz),
130.3 (d, Jp‑c = 8.0 Hz), 128.7, 128.6, 37.6 (d, Jp‑c = 65.8 Hz). 31P NMR
(162 MHz, CDCl3): δ 29.6. This compound is known.26c
J
p‑c = 9.1 Hz), 132.3 (d, Jp‑c = 103.7 Hz), 132.0 (d, Jp‑c = 2.4 Hz), 131.2
(d, Jp‑c = 9.4 Hz), 128.6 (d, Jp‑c = 9.3 Hz), 128.4 (d, Jp‑c = 12.2 Hz),
125.3 (d, Jp‑c = 2.8 Hz). 31P NMR (162 MHz, CDCl3): δ 21.4. This
compound is known.27d
Naphthalen-2-yldiphenylphosphine Oxide (2-2g). White solid:
59.0 mg, 90% yield. 1H NMR (400 MHz, CDCl3): δ 8.27 (d, 1H, J =
14.0 Hz), 7.89−7.83 (m, 3H), 7.72−7.68 (m, 4H), 7.65−7.60 (m, 1H),
7.56−7.49 (m, 4H), 7.46−7.42 (m, 4H). 13C {1H} NMR (100 MHz,
CDCl3): δ 134.8 (d, Jp‑c = 1.6 Hz), 134.1 (d, Jp‑c = 9.3 Hz), 132.6 (d, Jp‑c
= 103.8 Hz), 132.5 (d, Jp‑c = 13.0 Hz), 132.2 (d, Jp‑c = 9.8 Hz), 132.1 (d,
Jp‑c = 2.2 Hz), 129.7 (d, Jp‑c = 103.7 Hz), 129.1, 128.7 (d, Jp‑c = 12.0
Hz),128.5, 128.4, 127.9, 127.1, 126.9 (d, Jp‑c = 10.6 Hz). 31P NMR (162
MHz, CDCl3): δ 29.9. This compound is known.27a
Isopropyldiphenylphosphine Oxide (2-1e). White solid: 29.3 mg,
60% yield. 1H NMR (400 MHz, CDCl3): δ 7.80−7.75 (m, 4H), 7.50−
7.43 (m, 6H), 2.56−2.47 (m, 1H), 1.17 (dd, 6H, J1 = 16.4 Hz, J2 = 7.2
Hz). 13C {1H} NMR (100 MHz, CDCl3): δ 132.4 (d, Jp‑c = 94.1 Hz),
131.6 (d, Jp‑c = 2.0 Hz), 131.1 (d, Jp‑c = 8.5 Hz), 128.6 (d, Jp‑c = 11.0
Hz), 27.2 (d, Jp‑c = 72.4 Hz), 15.3. 31P NMR (162 MHz, CDCl3): δ
37.6. This compound is known.26d
Diphenyl(1-phenylethyl)phosphine Oxide (2-1f). White solid: 50.2
1
mg, 82% yield. H NMR (400 MHz, CDCl3): δ 7.91−7.86 (m, 2H),
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01642.
■
7.54−7.46 (m, 3H), 7.44−7.41 (m, 2H), 7.35−7.31 (m, 1H), 7.26−
7.12 (m, 7H), 3.63−3.55 (m, 1H), 1.57 (dd, 3H, J1 = 16.0 Hz, J2 = 7.2
Hz). 13C {1H} NMR (100 MHz, CDCl3): δ 138.0 (d, Jp‑c = 5.3 Hz),
132.5 (d, J = 13.7 Hz), 131.8 (d, Jp‑c = 2.1 Hz), 131.6 (d, Jp‑c = 9.9 Hz),
131.5 (d, Jp‑c = 8.4 Hz), 131.4 (d, Jp‑c = 2.5 Hz), 131.2 (d, Jp‑c = 8.8 Hz),
129.3 (d, Jp‑c = 5.5 Hz), 128.7 (d, Jp‑c = 11.1 Hz), 128.3 (d, Jp‑c = 1.3
Hz), 128.1 (d, Jp‑c = 11.4 Hz),127.0 (d, Jp‑c = 1.8 Hz), 41.0 (d, Jp‑c = 66.8
Hz), 15.5. 31P NMR (162 MHz, CDCl3): δ 34.1. This compound is
known.26a
sı
GC-MS spectra of results of comparation experiments
associated with Na, Li, K; the verification experiments for
compound 9; and copies of 1H, 13C, and 31P NMR spectra
for products (PDF)
Diphenyl(p-tolyl)phosphine Oxide (2-2a). White solid: 49.7 mg,
85% yield. 1H NMR (400 MHz, CDCl3): δ 7.66−7.61 (m, 4H), 7.55−
7.48 (m, 4H), 7.44−7.39 (m, 4H), 7.25−7.22 (m, 2H), 2.37 (s, 3H).
13C {1H} NMR (100 MHz, CDCl3): δ 142.6 (d, Jp‑c = 2.6 Hz), 132.8
(d, Jp‑c = 103.7 Hz), 132.2 (d, Jp‑c = 9.7 Hz), 132.1 (d, Jp‑c = 9.7 Hz),
AUTHOR INFORMATION
Corresponding Author
■
Li-Biao Han − National Institute of Advanced Industrial Science
and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan;
132.0 (d, Jp‑c = 2.4 Hz), 129.6, 129.4 (d, Jp‑c = 12.5 Hz), 128.5 (d, Jp‑c
=
F
https://dx.doi.org/10.1021/acs.joc.0c01642
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
Containing Poly(pyridinium salt)s as Fire Retardant Materials.
Polymers 2019, 11, 1141. (c) Plotnikova, G.; Malysheva, S.;
Gusarova, N.; Khalliulin, A.; Udilov, V.; Kuznetsov, K. Triorganyl-
phosphine Oxides as High-Performance Fire Retardants for Polyvinyl
Chloride Plastisols. Russ. J. Appl. Chem. 2008, 81, 304−309.
Division of Chemistry, Faculty of Pure and Applied Sciences,
University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan;
orcid.org/0000-0001-5566-9017; Email: libiao-han@
aist.go.jp
(4) (a) Ivanova, N.; Gusarova, N.; Reutskaya, A.; Shaikhutdinova, S.;
Arbuzova, S.; Trofimov, B. Tertiary Phosphine Oxides in Reaction with
Benzaldehyde. Russ. J. Gen. Chem. 2003, 73, 877−879. (b) Kazantseva,
M.; Timokhin, B.; Rokhin, A.; Blazhev, D.; Golubin, A.; Rybakova, Y. V.
New Aspect of Nucleophilic Reactivity of Tertiary Phosphine Oxides.
R3PO-POCl3 Binary System. Russ. J. Gen. Chem. 2001, 71, 1233−1235.
(c) Chu, T.; Vyboishchikov, S. F.; Gabidullin, B. M.; Nikonov, G. I.
Unusual Reactions of Nacnacal with Urea and Phosphine Oxides. Inorg.
Chem. 2017, 56, 5993−5997.
Authors
Jian-Qiu Zhang − National Institute of Advanced Industrial
Science and Technology (AIST), Tsukuba, Ibaraki 305-8565,
Japan; Division of Chemistry, Faculty of Pure and Applied
Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571,
Japan; orcid.org/0000-0002-5220-3200
Eiichi Ikawa − Katayama Chemical Industries Co., Ltd.,
Amagasaki, Hyogo 660-0892, Japan
Hiroyoshi Fujino − Katayama Chemical Industries Co., Ltd.,
Amagasaki, Hyogo 660-0892, Japan
Yuki Naganawa − National Institute of Advanced Industrial
Science and Technology (AIST), Tsukuba, Ibaraki 305-8565,
Japan; orcid.org/0000-0002-3041-7638
Yumiko Nakajima − Division of Chemistry, Faculty of Pure and
Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-
8571, Japan; orcid.org/0000-0001-6813-8733
(5) (a) Kotani, S.; Nakajima, M. Recent Advances in Asymmetric
Phosphine Oxide Catalysis. Tetrahedron Lett. 2020, 61, 151421.
́
(b) Beddoe, R. H.; Andrews, K. G.; Magne, V.; Cuthbertson, J. D.;
Saska, J.; Shannon-Little, A. L.; Shanahan, S. E.; Sneddon, H. F.;
Denton, R. M. Redox-neutral Organocatalytic Mitsunobu Reactions.
Science 2019, 365, 910−914.
(6) For C−P bond formations, see the recent summary in the
literature: Liu, C.; Szostak, M. Decarbonylative Phosphorylation of
Amides by Palladium and Nickel Catalysis: the Hirao Cross-Coupling
of Amide Derivatives. Angew. Chem., Int. Ed. 2017, 56, 12718−12722.
(7) (a) Byrne, P. A.; Gilheany, D. G. The Modern Interpretation of the
Wittig Reaction Mechanism. Chem. Soc. Rev. 2013, 42, 6670−6696.
(b) Maryanoff, B. E.; Reitz, A. B. The Wittig Olefination Reaction and
Modifications Involving Phosphoryl-Stabilized Carbanions. Stereo-
chemistry, Mechanism, and Selected Synthetic Aspects. Chem. Rev.
1989, 89, 863−927.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01642
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(8) (a) Hughes, D. L. Progress in the Mitsunobu Reaction. A Review.
Org. Prep. Proced. Int. 1996, 28, 127−164. (b) But, T. Y. S.; Toy, P. H.
The Mitsunobu Reaction: Origin, Mechanism, Improvements, and
Applications. Chem. - Asian J. 2007, 2, 1340−1355. (c) Fletcher, S. The
Mitsunobu Reaction in the 21 st Century. Org. Chem. Front. 2015, 2,
739−752.
(9) (a) Appel, R. Tertiary Phosphane/tetrachloromethane, A
Versatile Reagent for Chlorination, Dehydration, and P-N linkage.
Angew. Chem., Int. Ed. Engl. 1975, 14, 801−811. (b) Li, J. J. Appel
reaction. In Name Reactions: A Collection of Detailed Reaction
Mechanisms; Springer: Berlin, 2006; pp 10−11.
(10) (a) Hartley, F. R. The Chemistry of Organophosphorus
Compounds: Phosphine Oxides, Sulphides, Selenides and Tellurides;
Wiley-Blackwell, 1990; Vol. 2, pp 9−11. (b) Cottrell, T. L. The
strengths of chemical bonds; Butterworths Scientific Publications, 1958.
(11) (a) van Kalkeren, H. A.; van Delft, F. L.; Rutjes, F. P.
Organophosphorus Catalysis to Bypass Phosphine Oxide Waste.
ChemSusChem 2013, 6, 1615−1624. (b) Emery, R. J.; Papadaki, M.;
dos Santos, L. M. F.; Mantzavinos, D. Extent of Sonochemical
Degradation and Change of Toxicity of a Pharmaceutical Precursor
(Triphenylphosphine Oxide) In Water as A Function of Treatment
Conditions. Environ. Int. 2005, 31, 207−211.
(12) Compound 2′(Na) was generated via the cleavage of Ph3P(O)’s
P−Ph bond by sodium, while 3′(Na) was from the reaction of Ph3P(O)
with PhNa, and 4′(Na) was from the reduction of 3′(Na) by sodium.
See: (a) Zhang, J.-Q.; Ye, J.; Huang, T.; Shinohara, H.; Fujino, H.; Han,
L.-B. Conversion of Triphenylphosphine Oxide to Organophosphorus
via Selective Cleavage of C-P, O-P, and C-H Bonds with Sodium.
Commun. Chem. 2020, 3, 1. (b) SD can be purchased from TCI, etc.
Caution! Although declared safer than lump sodium, still SD is a dangerous
chemical that must be handled carefully by an expert. For its SDS, see:
https://www.tcichemicals.com/JP/ja/p/D5792 (SD).
■
This study was partially supported by a joint research of the
National Institute of Advanced Industrial Science and
Technology (AIST) with Katayama Chemical Industries Co.,
Ltd. We thank Kobelco Eco-Solutions Co., Ltd. for providing SD
samples.
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