Nickel-catalyzed coupling of R2P(O)Me (R = aryl or alkoxy) with (hetero)arylmethyl alcohols

Article abstract of DOI:10.1039/d1ob00086a

α-Alkylation of methyldiarylphosphine oxides with (hetero)arylmethyl alcohols was performed under nickel catalysis. Various arylmethyl and heteroarylmethyl alcohols can be used in this transformation. A series of methyldiarylphosphine oxides were alkylated with 30-90% yields. Functional groups on the aromatic rings of methyldiarylphosphine oxides or arylmethyl alcohols including OMe, NMe₂, SMe, CF₃, Cl, and F groups can be tolerated. The conditions are also suitable for the α-alkylation reaction of dialkyl methylphosphonates.

Full text of DOI:10.1039/d1ob00086a

Organic &
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Nickel-catalyzed coupling of R2P(O)Me (R = aryl or
alkoxy) with (hetero)arylmethyl alcohols†
Cite this: Org. Biomol. Chem., 2021,
19, 2233
Wei-Ze Lia and Zhong-Xia Wang
*
a,b
α-Alkylation of methyldiarylphosphine oxides with (hetero)arylmethyl alcohols was performed under
nickel catalysis. Various arylmethyl and heteroarylmethyl alcohols can be used in this transformation. A
series of methyldiarylphosphine oxides were alkylated with 30–90% yields. Functional groups on the aro-
matic rings of methyldiarylphosphine oxides or arylmethyl alcohols including OMe, NMe2, SMe, CF3, Cl,
and F groups can be tolerated. The conditions are also suitable for the α-alkylation reaction of dialkyl
methylphosphonates.
Received 18th January 2021,
Accepted 15th February 2021
DOI: 10.1039/d1ob00086a
rsc.li/obc
Arbuzov reaction are well known.10 Transition-metal-catalyzed
Introduction
methods to construct C–P bonds via cleavage of C–halide,11 C–
Reactions of C–C bond formation are important transform- O,12 C–N,13 C–S,14 C–CN15 and C–H16 bonds have also achieved
ations in organic synthesis. Among the reactions, transition- great success. However, the reported methods are not flawless.
metal-catalyzed cross-coupling of organometallic reagents with It is still desirable to develop new methodologies to overcome
electrophiles has attracted great attention. The electrophiles the drawbacks of the reported methods and extend the range
employed in the reactions are often organic halides or alcohol of reaction materials. As mentioned above, alcohols are widely
derivatives such as carboxylates, carbonates, and sulfonates.1 available and green starting materials. Synthesizing organo-
Direct use of alcohols was relatively rare due to the poor phosphorus compounds via reaction of alcohols with appropri-
leaving ability of the OH group. However, direct use of alcohols ate phosphorus substrates is attractive. Herein we report
as coupling partners is more step- and atom-economical α-alkylation of methyldiarylphosphine oxides or dialkyl
because organic halides and alcohol derivatives were mainly methylphosphonates with alcohols under catalysis with nickel
prepared from alcohols. In recent years, transition-metal-cata- complexes.
lyzed α-alkylation reactions using alcohols with hydrogen bor-
rowing methodologies have achieved significant advances.2
Nucleophilic substrates included acetones,3 nitriles,4 amides,5
Results and discussion
alcohols6 and other compounds containing active hydrogens.7
The catalysts employed for the above transformations were
mainly Ir, Ru, Rh, Os and Pd complexes.2 The use of non-
precious metal catalysts such as Fe, Mn, and Ni was relatively
rare.3e–h,7b–d,8
Methyldiphenylphosphine oxide 1a and benzyl alcohol 2a were
employed as model substrates to screen catalysts and reaction
conditions. We chose non-precious metals including copper,
cobalt, and nickel for testing (Table 1). CuCl2 was found to be
able to catalyze the reaction in the presence of t-BuOK in
toluene at 130 °C. Co(acac)2 was inactive under the same con-
ditions. Ni(COD)2 led to a better result than CuCl2 (entries
1–3). Hence we further tested nickel compounds. Ni(II) com-
pounds including Ni(dppe)Cl2, Ni(DME)Cl2 and Ni(glyme)Cl2
exhibited lower activity than Ni(COD)2 (entries 4–6).
Subsequently, we examined the base effect using Ni(COD)2 as
the catalyst. t-BuOLi, t-BuONa, NaOH, Cs2CO3, and K2CO3 were
respectively tested and these bases were demonstrated to be
less effective than t-BuOK (entries 7–11). The solvent also
markedly affected the reaction results. MeCN, 1,4-dioxane,
THF and cyclopentyl methyl ether (CPME) were examined and
CPME was demonstrated to be optimal (entries 12–15). Next,
we tried to improve the catalysis of Ni(COD)2 by adding
Organophosphorus compounds have found wide appli-
cations in many fields such as organic synthesis, coordination
chemistry, medicinal chemistry and photoelectric materials.9 A
series of methodologies have been developed to prepare
various phosphorus-containing compounds. Traditional
methods including radical methods, anionic methods and the
aCAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
E-mail: zxwang@ustc.edu.cn; Tel: +86 551 63603043
bCollaborative Innovation Center of Chemical Science and Engineering, Tianjin
300072, P. R. China
†Electronic supplementary information (ESI) available: Copies of NMR spectra.
See DOI: 10.1039/d1ob00086a
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Table 1 Optimization of reaction conditionsa
Entry
Cat.
L (mol%)
Solvent
Base
T (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
CuCl2
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
CH3CN
1,4-Dioxane
THF
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
CPME
t-BuOK
t-BuOK
t-BuOK
t-BuONa
t-BuONa
t-BuONa
t-BuOLi
t-BuONa
NaOH
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
140
120
140
140
140
140
140
140
140
140
140
140
140
40
Trace
54
8
10
20
8
48
46
—
Co(acac)2
Ni(COD)2
Ni(dppe)Cl2
Ni(DME)Cl2
Ni(glyme)Cl2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
—
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25c
26d
27d
28d
29d,e
30d, f
31d,g
32d,h
33d,i
34d
Cs2CO3
K2CO3
—
—
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
Trace
35
60
78
57
42
31
52
71
80
65
83
68
65
68
85
61
65
73
53
34
—
PPh3 (20)
PCy3 (20)
DPEPhos (10)
Dppp (10)
Dppe (10)
Dppb (10)
Dppb (10)
Dppb (10)
PPh3 (20)
Dppb (10)
IPr·HCl (20)
SMes·HCl (20)
IMes·HCl (20)
IMes·HCl (20)
IMes·HCl (20)
IMes·HCl (20)
IMes·HCl (20)
IMes·HCl (20)
IMes·HCl (20)
a Unless otherwise noted, all reactions were performed using the following reaction conditions: methyl diphenylphosphine oxide (0.25 mmol),
benzyl alcohol (0.625 mmol), base (0.25 mmol), solvent (1 cm3), and catalyst (10 mol%), 24 h. b Isolated yield. c Reaction time was 18 h.
d 0.3 mmol of t-BuOK was used. e 5 mol% of Ni(COD)2 and 10 mol% of IMes·HCl were used. f 0.25 mmol of benzyl alcohol was used. g 0.5 mmol
of benzyl alcohol was used. h 0.175 mmol of t-BuOK was employed. i 0.075 mmol of t-BuOK was employed.
ligands. Phosphine ligands including PPh3, PCy3, DPEPhos, 30–33). In addition, in the absence of Ni(COD)2 the reaction
dppp, dppe and dppb were used and both dppb and PPh3 led cannot occur (entry 34).
to better results than the other phosphine ligands (entries
Ni(COD)2-dppb, Ni(COD)2-PPh3 and Ni(COD)2-IMes systems
16–21). When the reaction temperature was raised to 140 °C, showed good catalytic properties under the optimized con-
the Ni(COD)2/dppb and Ni(COD)2/PPh3-catalyzed reaction gave ditions of temperature, time and solvent (entries 22, 24 and
a little higher product yields than the corresponding reactions 28, Table 1). We chose a Ni(COD)2–IMes combination as the
performed at 130 °C. When the reaction was run at 120 °C, the catalyst to examine substrate scope. (Hetero)arylmethyl alco-
product yield markedly decreased (entries 22–24). Reducing hols were first evaluated using methyldiphenylphosphine
the reaction time also led to a decrease of product yield (entry oxide 1a as the coupling partner (Table 2). Alkyl-substituted
25). Thereafter, we found that N-heterocyclic carbene ligands arylmethyl alcohols including p-tolylmethanol, (4-(tert-butyl)-
including IPr, SMes, and IMes were also effective at improving phenyl)methanol, and (2,4-dimethylphenyl)methanol reacted
the catalysis of Ni(COD)2. The combination of Ni(COD)2 smoothly with 1a, affording the corresponding products in
(10 mol%) and IMes (20 mol%) resulted in the highest product 70%, 65% and 79% yields, respectively (entries 1–3). The steric
yield (entries 26–28). Decreasing the loading of the catalyst led hindrance of (2,4-dimethylphenyl)methanol did not affect the
to a decrease of product yield (entry 29). We also tried to reaction. Conversely, its reaction with 1a gave the highest
decrease the dosage of benzyl alcohol and t-BuOK employed in product yield (79%). The reaction of (4-(methylthio)phenyl)
the reaction. In each case the product yield decreased (entries methanol with 1a gave comparable product yield to that of
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Table 2 Scope of reaction substratesa
p-tolylmethanol (entry 4). Both (4-methoxyphenyl)methanol
and (3-methoxyphenyl)methanol exhibited similar reactivity, and
they were more reactive than (4-(methylthio)phenyl)methanol
(entries 5 and 6). Arylmethyl alcohols with conjugated or
extended aromatic systems showed higher reactivity than aryl-
methyl alcohols with alkyl or alkoxy substituents on the aromatic
rings (entries 7–9). Arylmethyl alcohols with electron-withdrawing
groups such as Cl, F, and CF3 on the aromatic rings showed
lower reactivity (entries 10–13). We also noted that the combi-
nation of Ni(COD)2 and PPh3 showed better catalytic activity than
the combination of Ni(COD)2 and IMes in these cases. The reac-
tion of heteroarylmethanols including furan-2-ylmethanol, thio-
phen-2-ylmethanol and benzo[b]thiophen-2-ylmethanol with 1a
gave the desired products in modest yields (entries 14–16). The
reaction of pyridin-2-ylmethanol with 1a under the same con-
ditions resulted in an unidentified product. In addition,
common aliphatic alcohols such as butanol and cyclohexanol
cannot be used to replace benzyl alcohols in this transformation.
Next, we examined the reaction of several diarylmethyl-phos-
phine oxides with benzyl alcohol (Table 3). Diarylmethylphosphine
oxides with Me, NMe2 and OMe groups on the aromatic rings
reacted smoothly with benzyl alcohol under the standard con-
ditions, giving the corresponding products in 63–66% yields
(entries 1–3). Methyldi(naphthalen-2-yl)phosphine oxide
exhibited higher reactivity. Its reaction with benzyl alcohol
afforded the coupling product in 82% yield (entry 4).
Entry
1
Product
Yieldb (%)
70
2
3
65
79
4
5
6
73
80
82
7
8
88
90
Dialkyl
methylphosphonates
such
as
dimethyl-
methylphosphonate and diethyl methylphosphonate can also
react with arylmethyl alcohols (Table 4). However, they showed
lower reactivity than the diarylmethylphosphine oxides. The
reaction of dimethyl methylphosphonate and diethyl methyl-
phosphonate with benzyl alcohol resulted in the coupling pro-
9
87
10c
11c
53
54
Table 3 Reaction of diarylmethylphosphine oxides with benzyl
alcohola
12c
30
13c
14
45
53
Entry
1
Product
Yieldb (%)
63
15
16
54
49
2
3
63
66
a Unless otherwise noted, the reactions were carried out using
0.25 mmol of 1a and 0.625 mmol of arylmethyl alcohols according to
the conditions indicated by the above equation. b Isolated yield.
c 20 mol% of PPh3 and 0.25 mmol of t-BuOK were employed.
4
82
a The reactions were carried out using 0.25 mmol of 1 and 0.625 mmol
of benzyl alcohol according to the conditions indicated by the above
equation. b Isolated yield.
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Table 4 Reaction of dialkyl methylphosphonates with arylmethyl
alcoholsa
Entry
1
Product
Yieldb (%)
43
2
3
45
48
4
5
50
37
a The reactions were carried out using 0.25 mmol of 1 and 0.625 mmol
of benzyl alcohol according to the conditions indicated by the above
equation. b Isolated yield.
Scheme 3 Mechanistic studies.
nickel catalyst. The reaction of 5 with PhCH2OH under the
standard conditions afforded the coupling product 3a in 88%
NMR yield (Scheme 3b). In the absence of t-BuOK the reaction
of 5 with PhCH2OH gave the same result as that shown in
Scheme 3b (Scheme 3c). These experimental facts imply that a
nickel hydride complex was in situ formed.2 We observed the
formation of PhCHO via the reaction of L2Ni(0) with
PhCH2OH, but the Ni–H species was not detected by the 1H
NMR spectral study. This is ascribed to the instability of the
Ni–H species.18 In addition, the reaction of 1a with PhCD2OH
(93% D) under the standard conditions afforded 3a–d in 76%
yield along with 18–56% deuterium incorporation
(Scheme 3d). This study also suggests that the hydride source
is derived from alcohol for the reduction step and the transfer-
hydrogenation step is reversible. Based on the above experi-
mental results and literature reports8d,19 we propose a reaction
pathway as shown in Scheme 4. Thus, the reaction of the Ni
ducts in 43% and 45% yields, respectively (entries 1 and 2).
The reaction of other arylmethyl alcohols gave similar results
(entries 3–5).
To evaluate the synthetic applicability of this method, a
gram scale reaction between methyldiphenylphosphine oxide
and benzyl alcohol was carried out (Scheme 1). The coupling
product 3a was isolated in 80% yield. This result well demon-
strated the synthetic value of this reaction.
The compounds obtained by this approach can be further
converted to other important phosphorus-containing com-
pounds such as phosphines. For example, 3a was reduced with
HSiCl3 in the presence of Et3N to afford Ph2PCH2CH2Ph in
83% yield (Scheme 2).17
To gain insight into the reaction mechanism, several
control experiments were carried out. Condensation of diphe-
nyl(methyl)phosphine oxide with PhCHO in the presence of
t-BuOK gave diphenyl(styryl)phosphine oxide (5) in 74% yield
(Scheme 3a). This reaction did not require the presence of a
Scheme 1 Gram scale reaction of Ph2P(O)CH3 with PhCH2OH.
Scheme 2 Reduction of Ph2P(O)CH2CH2Ph with HSiCl3.
2236 | Org. Biomol. Chem., 2021, 19, 2233–2242
Scheme 4 Proposed reaction mechanism.
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complex with arylmethyl alcohol generates aryl aldehyde B and heated at 60 °C for 1 h, then cooled to room temperature,
a Ni–H intermediate. Condensation of the aryl aldehyde with diluted with water (25 cm3), and extracted with EtOAc (10 cm3
diaryl(methyl)phosphine oxide in the presence of t-BuOK pro- × 3). The combined extract was dried with sodium sulfate and
duces diaryl(alkenyl)phosphine oxide C. The reaction of C with concentrated under reduced pressure. The residue was purified
the Ni–H species affords the final coupling product D and by column chromatography on silica gel to give the corres-
regenerates the active Ni catalyst.
ponding product.
Methyldi-p-tolylphosphine oxide. White solid (0.73 g, 100%),
mp 136 °C. 1H NMR (400 MHz, CDCl3): δ 7.60 (dd, J = 11.8, 8.1
Hz, 4H), 7.26 (dd, J = 8.2, 2.2 Hz, 4H), 2.37 (s, 6H), 1.97 (d, J =
13.1 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 142.00 (d, J = 2.8
Hz), 130.95 (d, J = 103.9 Hz), 130.43 (d, J = 10.1 Hz), 129.25 (d,
J = 12.3 Hz), 21.46, 16.66 (d, J = 74.0 Hz). 31P NMR (162 MHz,
CDCl3): δ 29.97. HRMS (APCI): m/z 245.1088 [M + H]+, calcd for
C15H18OP 245.1090.
Conclusions
In summary, we developed a method to perform catalytic coup-
ling of methyldiarylphosphine oxides or dialkyl methyl-
phosphonates with (hetero)arylmethyl alcohols. The reaction
proceeded under nickel catalysis, gave the products in moder-
ate to high yields and was suited for a broad scope of sub-
strates. Functional groups on the aromatic rings of methyl-
diarylphosphine oxides or arylmethyl alcohols such as OMe,
NMe2, SMe, CF3, Cl, and F groups can be tolerated. This reac-
tion provides an efficient and green protocol to synthesize
complex phosphorus-containing molecules from simple phos-
phorus compounds. The reaction is believed to proceed via a
hydrogen-borrowing process.
Bis(4-(dimethylamino)phenyl)(methyl)phosphine
oxide.
White solid (0.81 g, 90%), mp 68–69 °C. 1H NMR (400 MHz,
CDCl3): δ 7.53 (dd, J = 11.3, 8.9 Hz, 4H), 6.70 (d, J = 8.6 Hz,
4H), 2.99 (d, J = 1.6 Hz, 12H), 1.90 (d, J = 13.0 Hz, 3H). 13C
NMR (101 MHz, CDCl3): δ 152.18, 131.95 (d, J = 11.1 Hz),
119.88 (d, J = 112.3 Hz), 111.38 (d, J = 12.6 Hz), 40.08, 17.26 (d,
J = 74.7 Hz). 31P NMR (162 MHz, CDCl3): δ 30.59. HRMS
(APCI): m/z 303.1622 [M + H]+, calcd for C17H24ON2P 303.1621.
Bis(3-methoxyphenyl)(methyl)phosphine oxide. Colorless oil
1
(0.74 g, 90%). H NMR (500 MHz, CDCl3): δ 7.40–7.34 (m, 2H),
7.34–7.32 (m, 1H), 7.31–7.29 (m, 1H), 7.24 (dd, J = 11.6, 7.5 Hz,
2H), 7.04 (dd, J = 8.3, 2.6 Hz, 2H), 3.81 (s, 6H), 2.01 (d, J = 13.3
Hz, 3H). 13C NMR (126 MHz, CDCl3): δ 159.63 (d, J = 14.7 Hz),
135.21 (d, J = 100.9 Hz), 129.87 (d, J = 14.2 Hz), 122.46 (d, J =
10.1 Hz), 117.80 (d, J = 2.6 Hz), 115.50 (d, J = 10.3 Hz), 55.40,
16.55 (d, J = 73.7 Hz). 31P NMR (202 MHz, CDCl3) δ 30.48.
HRMS (APCI): m/z 277.0988 [M + H]+, calcd for C15H18O3P
277.0988.
Experimental
All reactions were performed under a nitrogen atmosphere
using standard Schlenk and vacuum line techniques. Di-p-
tolylphosphine oxide, bis(4-(dimethylamino)phenyl)phos-
phine oxide, bis(3-methoxyphenyl)phosphine oxide, and di
(naphthalen-2-yl)phosphine oxide were prepared according to
the reported procedure.20 Ni(COD)2 was purchased from Alfa
Aesar and used as received. The phosphine ligands and the
NHC precursors were purchased from Energy Chemical and
used as received. CPME (extra dry) was purchased from Energy
Chemical and degassed prior to use. Other chemicals were
obtained from commercial vendors. Toluene and tetrahydro-
furan were purified using JC Meyer Phoenix Solvent Systems.
1,4-Dioxane was distilled under nitrogen over sodium and
degassed prior to use. MeCN was dried over 4 Å molecular
sieves, then fractionally distilled, and stored under a nitrogen
atmosphere. NMR spectra were recorded on a Bruker AV400 or
Bruker AV500 spectrometer at 25 °C. The chemical shifts of the
1H NMR spectra were referenced to TMS; the chemical shifts
of the 13C NMR spectra were referenced to internal solvent
resonances. The chemical shifts of 31P NMR spectra were refer-
enced to external phosphoric acid, and the chemical shifts of
19F NMR spectra were referenced to external trifluoroacetic
acid. High-resolution mass spectra (HRMS) were acquired on a
Thermo Fisher LTQ Orbitrap XL mass spectrometer.
Methyldi(naphthalen-2-yl)phosphine oxide. White solid
1
(0.87 g, 92%), mp 178 °C. H NMR (400 MHz, CDCl3): δ 8.41
(d, J = 13.6 Hz, 2H), 7.93–7.85 (m, 4H), 7.85–7.80 (m, 2H),
7.72–7.64 (m, 2H), 7.58–7.48 (m, 4H), 2.18 (d, J = 13.2 Hz, 3H).
13C NMR (101 MHz, CDCl3): δ 134.59 (d, J = 2.4 Hz), 132.49 (d,
J = 13.0 Hz), 132.30 (d, J = 9.1 Hz), 131.07 (d, J = 102.0 Hz),
128.83, 128.61 (d, J = 11.8 Hz), 128.14, 127.82, 127.01, 125.51
(d, J = 10.9 Hz), 16.51 (d, J = 74.1 Hz). 31P NMR (162 MHz,
CDCl3): δ 30.22. HRMS (APCI): m/z 317.1089 [M + H]+, calcd for
C21H18OP 317.1090.
Reaction of methyldiarylphosphine oxides with arylmethyl
alcohols
General procedure A. Methyldiarylphosphine oxide
(0.25 mmol), Ni(COD)2 (6.9 mg, 0.025 mmol), IMes·HCl
(17 mg, 0.05 mmol), t-BuOK (34 mg, 0.3 mmol), arylmethyl
alcohol (0.625 mmol) and CPME (1 cm3) were successively
charged into a Schlenk tube. The mixture was stirred at 140 °C
for 24 h and then cooled to room temperature. The resulting
mixture was concentrated to dryness under reduced pressure
Preparation of methyldiarylphosphine oxides21
To a stirred solution of diarylphosphine oxides (3 mmol) in and the residue was purified by column chromatography on
DMSO (10 cm3) was added a 50% aqueous solution of KOH silica gel to give the corresponding cross-coupling product.
(4 mmol) at 20 °C. To the mixture MeI (4 mmol) was added
General procedure B. Methyldiarylphosphine oxide
dropwise at 20 °C with stirring. The resulting mixture was (0.25 mmol), Ni(COD)2 (6.9 mg, 0.025 mmol), PPh3 (13 mg,
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0.05 mmol), t-BuOK (28 mg, 0.25 mmol), arylmethyl alcohol CDCl3): δ 7.81–7.71 (m, 4H), 7.56–7.43 (m, 6H), 7.08 (d, J = 8.6
(0.625 mmol) and CPME (1 cm3) were successively charged Hz, 2H), 6.80 (d, J = 8.6 Hz, 2H), 3.76 (s, 3H), 2.93–2.82 (m,
into a Schlenk tube. The mixture was stirred at 140 °C for 24 h 2H), 2.61–2.50 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 158.18,
and then cooled to room temperature. The resulting mixture 133.20, 132.86 (d, J = 98.5 Hz), 131.89 (d, J = 2.7 Hz), 130.87 (d,
was concentrated to dryness under reduced pressure and the J = 9.4 Hz), 129.11, 128.81 (d, J = 11.7 Hz), 114.09, 55.38, 32.21
residue was purified by column chromatography on silica gel (d, J = 69.8 Hz), 26.76 (d, J = 3.1 Hz). 31P NMR (162 MHz,
to give the corresponding cross-coupling product.
CDCl3): δ 31.75.
(3-Methoxyphenethyl)diphenylphosphine oxide (3g). Yellow
Phenethyldiphenylphosphine oxide (3a).15b White solid
1
(65 mg, 85%), mp 102–103 °C. H NMR (400 MHz, CDCl3): δ solid (68.9 mg, 82%), mp 125 °C. 1H NMR (400 MHz, CDCl3): δ
7.84–7.72 (m, 4H), 7.56–7.44 (m, 6H), 7.29–7.22 (m, 2H), 7.83–7.72 (m, 4H), 7.56–7.42 (m, 6H), 7.18 (t, J = 7.9 Hz, 1H),
7.21–7.13 (m, 3H), 2.99–2.88 (m, 2H), 2.64–2.53 (m, 2H). 13C 6.79–6.68 (m, 3H), 3.76 (s, 3H), 2.96–2.85 (m, 2H), 2.65–2.53
NMR (101 MHz, CDCl3): δ 141.23 (d, J = 15.4 Hz), 132.82 (d, J = (m, 2H). 13C NMR (101 MHz, CDCl3): δ 159.78, 142.81 (d, J =
98.7 Hz), 131.89 (d, J = 2.7 Hz), 130.84 (d, J = 9.4 Hz), 128.86, 15.4 Hz), 132.71 (d, J = 98.4 Hz), 131.89 (d, J = 2.7 Hz), 130.80
128.71 (d, J = 6.2 Hz), 128.12, 126.40, 31.95 (d, J = 70.1 Hz), (d, J = 9.4 Hz), 129.67, 128.78 (d, J = 11.7 Hz), 120.41, 113.88,
27.60 (d, J = 3.1 Hz). 31P NMR (162 MHz, CDCl3): δ 31.57.
111.67, 55.22, 31.85 (d, J = 69.9 Hz), 27.63 (d, J = 3.0 Hz). 31P
(4-Methylphenethyl)diphenylphosphine oxide (3b).22 White NMR (162 MHz, CDCl3): δ 31.63. HRMS (EI): m/z 336.1261
solid (56 mg, 70%), mp 124–125 °C. 1H NMR (400 MHz, [M]+, calcd for C21H21O2P 336.1274.
CDCl3): δ 7.81–7.71 (m, 4H), 7.57–7.43 (m, 6H), 7.06 (s, 4H),
(2-([1,1′-Biphenyl]-4-yl)ethyl)diphenylphosphine
oxide
2.95–2.84 (m, 2H), 2.62–2.51 (m, 2H), 2.29 (s, 3H). 13C NMR (3h).15b Yellow solid (84 mg, 88%), mp 171–173 °C. 1H NMR
(101 MHz, CDCl3): δ 138.15 (d, J = 15.6 Hz), 135.92, 132.82 (d, (400 MHz, CDCl3): δ 7.82–7.73 (m, 4H), 7.57–7.44 (m, 10H),
J = 98.3 Hz), 131.86 (d, J = 2.7 Hz), 130.84 (d, J = 9.3 Hz), 7.41 (t, J = 7.6 Hz, 2H), 7.32 (t, J = 7.3 Hz, 1H), 7.23 (d, J = 8.1
129.33, 128.78 (d, J = 11.6 Hz), 127.98, 32.06 (d, J = 69.7 Hz), Hz, 2H), 3.04–2.93 (m, 2H), 2.67–2.56 (m, 2H). 13C NMR
27.15 (d, J = 3.1 Hz), 21.06. 31P NMR (162 MHz, CDCl3): δ (101 MHz, CDCl3): δ 140.88, 140.28 (d, J = 15.1 Hz), 139.38,
31.71.
132.80 (d, J = 98.4 Hz), 131.89 (d, J = 2.7 Hz), 130.84 (d, J = 9.3
(4-(tert-Butyl)phenethyl)diphenylphosphine oxide (3c).22 Hz), 128.86, 128.81, 128.66 (d, J = 16.0 Hz), 127.38, 127.23,
White solid (58.8 mg, 65%), mp 114–116 °C. 1H NMR 127.04, 31.92 (d, J = 69.8 Hz), 27.27 (d, J = 3.1 Hz). 31P NMR
(400 MHz, CDCl3): δ 7.81–7.72 (m, 4H), 7.56–7.42 (m, 6H), 7.28 (162 MHz, CDCl3): δ 31.54.
(d, J = 8.2 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 2.98–2.85 (m, 2H),
(2-(Naphthalen-1-yl)ethyl)diphenylphosphine oxide (3i).22
2.65–2.52 (m, 2H), 1.29 (s, 9H). 13C NMR (101 MHz, CDCl3): δ Yellow solid (80.1 mg, 90%), mp 119–121 °C. 1H NMR
149.30, 138.19 (d, J = 15.4 Hz), 132.91 (d, J = 98.2 Hz), 131.89 (400 MHz, CDCl3): δ 7.88–7.76 (m, 6H), 7.69 (d, J = 8.0 Hz, 1H),
(d, J = 2.6 Hz), 130.88 (d, J = 9.3 Hz), 128.81 (d, J = 11.7 Hz), 7.56–7.42 (m, 8H), 7.34 (t, J = 7.5 Hz, 1H), 7.29 (d, J = 6.4 Hz,
127.83, 125.60, 34.49, 31.94 (d, J = 70.0 Hz), 31.47, 27.07 (d, J = 1H), 3.44–3.33 (m, 2H), 2.74–2.62 (m, 2H). 13C NMR (101 MHz,
3.0 Hz). 31P NMR (162 MHz, CDCl3): δ 31.79.
CDCl3): δ 137.31 (d, J = 14.8 Hz), 133.95, 132.81 (d, J = 98.6
(2,4-Dimethylphenethyl)diphenylphosphine oxide (3d). Hz), 131.94 (d, J = 2.7 Hz), 131.32, 130.86 (d, J = 9.4 Hz),
Yellow solid (65.9 mg, 79%), mp 104–105 °C. 1H NMR 128.95, 128.79 (d, J = 11.7 Hz), 127.28, 126.21, 125.87, 125.73,
(400 MHz, CDCl3): δ 7.82–7.73 (m, 4H), 7.56–7.43 (m, 6H), 7.00 125.65, 123.35, 31.23 (d, J = 69.7 Hz), 24.83 (d, J = 2.9 Hz). 31P
(d, J = 7.5 Hz, 1H), 6.95–6.89 (m, 2H), 2.91–2.81 (m, 2H), NMR (162 MHz, CDCl3): δ 31.66.
2.55–2.44 (m, 2H), 2.26 (s, 3H), 2.17 (s, 3H). 13C NMR
(2-(Naphthalen-2-yl)ethyl)diphenylphosphine oxide (3j).15b
(101 MHz, CDCl3): δ 136.39 (d, J = 15.2 Hz), 136.12, 135.65, White solid (77.4 mg, 87%), mp 145–146 °C. 1H NMR
132.86 (d, J = 98.1 Hz), 131.91 (d, J = 2.7 Hz), 131.28, 130.85 (d, (400 MHz, CDCl3): δ 7.83–7.70 (m, 7H), 7.59 (s, 1H), 7.38–7.55
J = 9.3 Hz), 128.80 (d, J = 11.6 Hz), 128.39, 126.96, 30.75 (d, J = (m, 8H), 7.29 (dd, J = 8.4, 1.7 Hz, 1H), 3.15–3.05 (m, 2H),
69.6 Hz), 24.58 (d, J = 3.0 Hz), 20.97, 19.15. 31P NMR 2.72–2.62 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 138.64 (d, J =
(162 MHz, CDCl3): δ 31.70. HRMS (EI): m/z 334.1468 [M]+, 15.3 Hz), 133.60, 132.77 (d, J = 98.8 Hz), 132.17, 131.93 (d, J = 2.7
calcd for C22H23OP 334.1481.
Hz), 130.87 (d, J = 9.3 Hz), 128.83 (d, J = 11.7 Hz), 128.36, 127.69,
(4-(Methylthio)phenethyl)diphenylphosphine oxide (3e). 127.50, 126.76, 126.23 (d, J = 5.9 Hz), 125.55, 31.82 (d, J = 70.1
Yellow solid (64.2 mg, 73%), mp 150–151 °C. 1H NMR Hz), 27.79 (d, J = 3.0 Hz). 31P NMR (162 MHz, CDCl3): δ 31.68.
(400 MHz, CDCl3): δ 7.80–7.72 (m, 4H), 7.57–7.43 (m, 6H), 7.16
(4-Chlorophenethyl)diphenylphosphine oxide (3k).22 White
(d, J = 8.3 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 2.94–2.84 (m, 2H), solid (46.8 mg, 55%), mp 146 °C. 1H NMR (500 MHz, CDCl3): δ
2.61–2.50 (m, 2H), 2.45 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 7.80–7.72 (m, 4H), 7.57–7.45 (m, 6H), 7.21 (d, J = 8.4 Hz, 2H),
138.26 (d, J = 15.3 Hz), 136.21, 132.80 (d, J = 98.7 Hz), 131.94 7.09 (d, J = 8.4 Hz, 2H), 2.96–2.86 (m, 2H), 2.60–2.50 (m, 2H).
(d, J = 2.7 Hz), 130.87 (d, J = 9.4 Hz), 128.90, 128.75 (d, J = 7.0 13C NMR (101 MHz, CDCl3): δ 139.59 (d, J = 15.0 Hz), 132.59
Hz), 127.29, 31.96 (d, J = 69.6 Hz), 27.14 (d, J = 3.0 Hz), 16.30. (d, J = 99.1 Hz), 132.14, 131.99 (d, J = 2.7 Hz), 130.81 (d, J = 9.4
31P NMR (162 MHz, CDCl3): δ 31.67. HRMS (ESI): m/z 375.0931 Hz), 129.55, 128.85 (d, J = 11.7 Hz), 128.74, 31.81 (d, J = 70.1
[M + Na]+, calcd for C21H21SOPNa 375.0943.
Hz), 27.04 (d, J = 3.0 Hz). 31P NMR (202 MHz, CDCl3): δ 31.27.
(2-Chlorophenethyl)diphenylphosphine oxide (3l). Yellow oil
(4-Methoxyphenethyl)diphenylphosphine
oxide
(3f).15b
White solid (67.2 mg, 80%), mp 87 °C. 1H NMR (400 MHz, (40.8 mg, 48%). 1H NMR (400 MHz, CDCl3): δ 7.84–7.74 (m
2238 | Org. Biomol. Chem., 2021, 19, 2233–2242
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4H), 7.57–7.43 (m, 6H), 7.33–7.28 (m, 1H), 7.25–7.19 (m, 1H), = 1.7 Hz). 31P NMR (162 MHz, CDCl3): δ 30.98. HRMS (ESI):
7.18–7.09 (m, 2H), 3.09–2.99 (m, 2H), 2.65–2.54 (m, 2H). 13C m/z 385.0789 [M + Na]+, calcd for C22H19OPSNa 385.0786.
NMR (101 MHz, CDCl3): δ 138.80 (d, J = 15.1 Hz), 133.75,
Phenethyldi-p-tolylphosphine oxide (3r).15b White solid
132.71 (d, J = 98.9 Hz), 131.95 (d, J = 2.7 Hz), 130.89 (d, J = 9.4 (52.6 mg, 63%), mp 98–99 °C. 1H NMR (400 MHz, CDCl3): δ
Hz), 130.58, 129.66, 128.79 (d, J = 11.7 Hz), 128.07, 127.25, 7.65 (d, J = 8.1 Hz, 2H), 7.63 (d, J = 8.1 Hz, 2H), 7.32–7.23 (m,
30.04 (d, J = 69.7 Hz), 26.24 (d, J = 2.6 Hz). 31P NMR (162 MHz, 6H), 7.21–7.14 (m, 3H), 2.96–2.86 (m, 2H), 2.59–2.49 (m, 2H),
CDCl3): δ 31.74. HRMS (EI): m/z 339.0694 [M]+, calcd for 2.39 (s, 6H). 13C NMR (101 MHz, CDCl3): δ 142.32 (d, J = 2.7
C20H18OP35Cl 340.0700.
Hz), 141.54 (d, J = 15.7 Hz), 130.93 (d, J = 9.7 Hz), 129.79 (d, J =
(2-Fluorophenethyl)diphenylphosphine oxide (3m). Yellow 101.2 Hz), 129.57 (d, J = 12.1 Hz), 128.72, 128.19, 126.39, 32.20
1
solid (24.3 mg, 30%), mp 94 °C. H NMR (400 MHz, CDCl3): δ (d, J = 70.1 Hz), 27.75 (d, J = 3.1 Hz), 21.71. 31P NMR (162 MHz,
7.83–7.73 (m, 4H), 7.56–7.43 (m, 6H), 7.21–7.12 (m, 2H), CDCl3): δ 31.90.
7.05–6.94 (m, 2H), 3.03–2.91 (m, 2H), 2.65–2.54 (m, 2H). 13C
Bis(4-(dimethylamino)phenyl)(phenethyl)phosphine oxide
NMR (101 MHz, CDCl3): δ 161.18 (d, J = 246.1 Hz), 132.70 (d, (3s).23 White solid (61.7 mg, 63%), mp 168 °C. 1H NMR
J = 99.1 Hz), 131.95 (d, J = 2.7 Hz), 130.88 (d, J = 9.3 Hz), 130.57 (400 MHz, CDCl3): δ 7.61–7.52 (m, 4H), 7.28–7.22 (m, 2H),
(d, J = 4.8 Hz), 128.84 (d, J = 11.7 Hz), 128.34 (d, J = 8.1 Hz), 7.20–7.14 (m, 3H), 6.71 (dd, J = 8.9, 2.0 Hz, 4H), 2.99 (s, 12H),
128.08, 124.35 (d, J = 3.5 Hz), 115.41 (d, J = 21.7 Hz), 30.39 (d, 2.95–2.86 (m, 2H), 2.52–2.42 (m, 2H). 13C NMR (101 MHz,
J = 70.3 Hz), 21.97 (t, J = 2.7 Hz). 19F NMR (376 MHz, CDCl3): δ CDCl3): δ 152.28, 142.11 (d, J = 15.8 Hz), 132.31 (d, J = 10.6
−118.46. 31P NMR (162 MHz, CDCl3): δ 31.84. HRMS (EI): m/z Hz), 128.58, 128.19, 126.12, 118.21 (d, J = 109.5 Hz), 111.53 (d,
324.1069 [M]+, calcd for C20H18FOP 324.1074.
J = 12.3 Hz), 40.12, 32.63 (d, J = 71.1 Hz), 28.05 (d, J = 2.7 Hz).
Diphenyl(4-(trifluoromethyl)phenethyl)phosphine
oxide 31P NMR (162 MHz, CDCl3): δ 33.46.
(3n).22 White solid (42.1 mg, 45%), mp 99 °C. 1H NMR
Bis(3-methoxyphenyl)(phenethyl)phosphine
oxide
(3t).
(400 MHz, CDCl3): δ 7.80–7.72 (m, 4H), 7.57–7.44 (m, 8H), 7.27 Colorless oil (60.4 mg, 66%). 1H NMR (400 MHz, CDCl3): δ
(d, J = 8.0 Hz, 2H), 3.05–2.96 (m, 2H), 2.63–2.54 (m, 2H). 13C 7.42–7.33 (m, 4H), 7.31–7.23 (m, 4H), 7.18 (t, J = 7.4 Hz, 3H),
NMR (101 MHz, CDCl3): δ 145.27 (d, J = 14.3 Hz), 132.62 (d, J = 7.05 (dd, J = 8.2, 2.5 Hz, 2H), 3.83 (s, 6H), 2.99–2.90 (m, 2H),
98.9 Hz), 132.08 (d, J = 2.8 Hz), 130.87 (d, J = 9.3 Hz), 128.92 2.61–2.51 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 159.78 (d, J =
(d, J = 11.7 Hz), 128.86 (q, J = 32.4 Hz), 128.63, 125.63 (q, J = 14.3 Hz), 141.20 (d, J = 15.5 Hz), 134.10 (d, J = 97.6 Hz), 130.01
3.8 Hz), 124.29 (q, J = 272.0 Hz), 31.66 (d, J = 70.1 Hz), 27.61 (d, J = 13.8 Hz), 128.67, 128.12, 126.40, 122.71 (d, J = 9.6 Hz),
(d, J = 3.0 Hz). 31P NMR (162 MHz, CDCl3): δ 31.07. 19F NMR 118.02, 115.81 (d, J = 9.9 Hz), 55.52, 32.01 (d, J = 70.0 Hz),
(376 MHz, CDCl3): δ −62.46.
27.64 (d, J = 2.9 Hz). 31P NMR (162 MHz, CDCl3): δ 31.88.
(2-(Furan-2-yl)ethyl)diphenylphosphine oxide (3o). Yellow HRMS (ESI): m/z 389.1265 [M + Na]+, calcd for C22H23O3PNa
solid (39.2 mg, 53%), mp 67–68 °C. 1H NMR (500 MHz, 389.1277.
CDCl3): δ 7.80–7.71 (m, 4H), 7.56–7.43 (m, 6H), 7.26 (d, J = 1.1
Di(naphthalen-2-yl)(phenethyl)phosphine oxide (3u).15b
1
Hz, 1H), 6.25–6.20 (m, 1H), 5.98 (d, J = 2.9 Hz, 1H), 3.01–2.91 Yellow solid (83.2 mg, 82%), mp 182 °C. H NMR (500 MHz,
(m, 2H), 2.68–2.58 (m, 2H). 13C NMR (101 MHz, CDCl3): δ CDCl3): δ 8.46 (d, J = 13.2 Hz, 2H), 7.96–7.88 (m, 4H), 7.85 (d, J
154.21 (d, J = 17.0 Hz), 141.41, 132.55 (d, J = 99.0 Hz), 131.98 = 7.7 Hz, 2H), 7.72 (t, J = 8.8 Hz, 2H), 7.61–7.49 (m, 4H), 7.25
(d, J = 2.7 Hz), 130.87 (d, J = 9.4 Hz), 128.85 (d, J = 11.7 Hz), (t, J = 7.4 Hz, 2H), 7.21–7.14 (m, 3H), 3.07–2.95 (m, 2H),
110.38, 105.58, 28.51 (d, J = 71.4 Hz), 20.51 (d, J = 2.5 Hz). 31P 2.84–2.72 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 141.34 (d, J =
NMR (162 MHz, CDCl3): δ 31.50. HRMS (EI): m/z 296.0952 15.4 Hz), 134.80 (d, J = 2.2 Hz), 133.02 (d, J = 8.4 Hz), 132.75
[M]+, calcd for C18H17O2P 296.0961.
(d, J = 12.7 Hz), 129.98 (d, J = 98.7 Hz), 129.03, 128.79 (d, J =
Diphenyl(2-(thiophen-2-yl)ethyl)phosphine oxide (3p).22 11.6 Hz), 128.77, 128.33, 128.24, 127.98, 127.17, 126.49, 125.70
Yellow solid (42.2 mg, 54%), mp 127–128 °C. 1H NMR (d, J = 10.6 Hz), 31.92 (d, J = 70.2 Hz), 27.79 (d, J = 3.0 Hz). 31P
(500 MHz, CDCl3): δ 7.82–7.72 (m, 4H), 7.58–7.44 (m, 6H), 7.11 NMR (162 MHz, CDCl3): δ 31.86.
(d, J = 4.8 Hz, 1H), 6.88 (dd, J = 5.0, 3.6 Hz, 1H), 6.79 (dd, J =
Dimethyl phenethylphosphonate (4a).24 Colorless oil
3.0 Hz, 1H), 3.20–3.10 (m, 2H), 2.72–2.62 (m, 2H). 13C NMR (19.8 mg, 37%). 1H NMR (500 MHz, CDCl3): δ 7.33–7.27 (m,
(126 MHz, CDCl3): δ 143.96 (d, J = 17.5 Hz), 132.52 (d, J = 99.0 2H), 7.24–7.17 (m, 3H), 3.73 (d, J = 10.8 Hz, 6H), 2.98–2.85 (m,
Hz), 132.07 (d, J = 2.6 Hz), 130.90 (d, J = 9.3 Hz), 128.91 (d, J = 2H), 2.15–2.01 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 140.92
11.8 Hz), 127.02, 124.66, 123.72, 32.29 (d, J = 69.8 Hz), 22.23 (d, J = 17.4 Hz), 128.73, 128.15, 126.54, 52.48 (d, J = 6.6 Hz),
(d, J = 2.2 Hz). 31P NMR (202 MHz, CDCl3): δ 31.21.
28.58 (d, J = 4.5 Hz), 26.75 (d, J = 139.9 Hz). 31P NMR
2-(2-Diphenylphosphorylethyl)benzothiophene (3q). Yellow (162 MHz, CDCl3): δ 33.41.
solid (44.0 mg, 49%), mp 122–123 °C. 1H NMR (400 MHz,
Diethyl phenethylphosphonate (4b).24 Colorless oil
CDCl3): δ 7.84–7.70 (m, 5H), 7.62 (d, J = 7.7 Hz, 1H), 7.56–7.44 (28.8 mg, 45%). 1H NMR (400 MHz, CDCl3): δ 7.32–7.26 (m,
(m, 6H), 7.33–7.21 (m, 2H), 7.00 (s, 1H), 3.29–3.17 (m, 2H), 2H), 7.25–7.16 (m, 3H), 4.18–4.03 (m, 4H), 2.99–2.85 (m, 2H),
2.79–2.66 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 144.82 (d, J = 2.13–1.98 (m, 2H), 1.32 (t, J = 7.1 Hz, 6H). 13C NMR (101 MHz,
17.0 Hz), 140.01, 139.41, 132.52 (d, J = 98.7 Hz), 132.09 (d, J = CDCl3): δ 140.98 (d, J = 17.4 Hz), 128.59, 128.06, 126.36, 61.62
2.4 Hz), 130.89 (d, J = 9.4 Hz), 128.90 (d, J = 11.7 Hz), 124.37, (d, J = 6.5 Hz), 28.61 (d, J = 4.4 Hz), 27.61 (d, J = 139.4 Hz),
123.91, 123.04, 122.24, 121.22, 31.72 (d, J = 70.1 Hz), 23.18 (d, J 16.49 (d, J = 6.0 Hz). 31P NMR (162 MHz, CDCl3): δ 30.80.
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Diethyl (4-methylphenethyl)phosphonate (4c).25 Colorless 0.30 mmol), benzaldehyde (67 mg, 0.625 mmol) and CPME
oil (31 mg, 48%). 1H NMR (400 MHz, CDCl3): δ 7.10 (s, 4H), (1 cm3) were successively charged into a Schlenk tube. The
4.18–4.02 (m, 4H), 2.93–2.82 (m, 2H), 2.32 (s, 3H), 2.10–1.98 mixture was stirred at 140 °C for 24 h and then concentrated
(m, 2H), 1.33 (t, J = 7.1 Hz, 6H). 13C NMR (101 MHz, CDCl3): δ to dryness under reduced pressure. The residue was purified
138.02 (d, J = 18.1 Hz), 135.95, 129.33, 128.00, 61.66 (d, J = 6.5 by column chromatography on silica gel to give diphenyl
1
Hz), 28.51 28.23 (d, J = 4.4 Hz), 27.13, 21.11, 16.58 (d, J = 6.1 (styryl)phosphine oxide (5)27 in 74% yield. H NMR (400 MHz,
Hz). 31P NMR (162 MHz, CDCl3): δ 30.97.
CDCl3): δ 7.82–7.72 (m, 4H), 7.59–7.51 (m, 5H), 7.51–7.46 (m,
Diethyl (4-methoxyphenethyl)phosphonate (4d).25 Colorless 4H), 7.41–7.35 (m, 3H), 6.84 (dd, J = 17.9, 14.0 Hz, 1H). 13C
1
oil (34 mg, 50%). H NMR (400 MHz, CDCl3): δ 7.12 (d, J = 8.5 NMR (101 MHz, CDCl3): δ 147.88 (d, J = 3.0 Hz), 135.23 (d, J =
Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 4.17–4.02 (m, 4H), 3.79 (s, 3H), 14.4 Hz), 132.88 (d, J = 85.3 Hz), 132.08 (d, J = 2.2 Hz), 131.56
2.92–2.80 (m, 2H), 2.09–1.96 (m, 2H), 1.32 (t, J = 7.1 Hz, 6H). 13
C
(d, J = 8.1 Hz), 130.28, 130.14, 129.00, 128.79 (d, J = 9.8 Hz),
NMR (101 MHz, CDCl3): δ 158.23, 133.17 (d, J = 17.8 Hz), 129.09, 128.39, 127.94, 119.13 (d, J = 84.1 Hz). 31P NMR (162 MHz,
114.06, 61.65 (d, J = 6.5 Hz), 55.39, 28.68, 27.82 (d, J = 4.5 Hz), CDCl3): δ 25.11.
27.30, 16.58 (d, J = 6.0 Hz). 31P NMR (162 MHz, CDCl3): δ 30.91.
Reaction of Ph2P(O)CHvCHPh with PhCH2OH under the
Diethyl (4-fluorophenethyl)phosphonate (4e). Colorless oil standard conditions. Ph2P(O)CHvCHPh (76 mg, 0.25 mmol),
1
(24 mg, 37%). H NMR (400 MHz, CDCl3): δ 7.21–7.12 (m, 2H), Ni(COD)2 (6.9 mg, 0.025 mmol), IMes·HCl (17 mg,
7.02–6.94 (m, 2H), 4.17–4.02 (m, 4H), 2.95–2.84 (m, 2H), 2.10–1.97 0.05 mmol), t-BuOK (34 mg, 0.30 mmol), benzyl alcohol
(m, 2H), 1.32 (t, J = 7.1 Hz, 6H). 13C NMR (101 MHz, CDCl3): δ (68 mg, 0.625 mmol), and CPME (1 cm3) were successively
161.51 (d, J = 244.2 Hz), 136.63 (dd, J = 17.4, 3.2 Hz), 129.54 (d, J = charged into a Schlenk tube. The mixture was stirred at 140 °C
7.9 Hz), 115.36 (d, J = 21.2 Hz), 61.66 (d, J = 6.5 Hz), 28.45, 27.89 for 24 h, cooled to room temperature, and concentrated to
(d, J = 4.4 Hz), 27.07, 16.51 (d, J = 6.0 Hz). 31P NMR (162 MHz, dryness under reduced pressure. The residue was purified by
CDCl3): δ 30.50. 19F NMR (376 MHz, CDCl3): δ −116.90. HRMS column chromatography on silica gel to give phenethyl-
(EI): m/z 260.0973 [M]+, calcd for C12H18O3FP 260.0972.
diphenyl phosphine oxide (3a) in 88% yield.
Reaction of Ph2P(O)CHvCHPh with PhCH2OH in the
absence of t-BuOK. IMes·HCl (17 mg, 0.05 mmol), t-BuOK
Gram scale reaction of Ph2P(O)CH3 with PhCH2OH
Methyldiphenylphosphine oxide (1.0 g, 4.63 mmol), Ni(COD)2 (5.6 mg, 0.05 mmol) and CPME (1 cm3) were successively
(127.79 mg, 0.463 mmol), PPh3 (240.76 mg, 0.926 mmol), charged into a Schlenk tube. After the mixture was stirred at
t-BuOK (518.56 mg, 4.63 mmol), benzyl alcohol (1.2 cm3, room temperature for 30 min, Ni(COD)2 (6.9 mg, 0.025 mmol)
11.58 mmol) and CPME (10 cm3) were successively charged was added. The resulting mixture was stirred for an additional
into a Schlenk tube. The mixture was stirred at 140 °C for 24 h 30 min. Ph2P(O)CHvCHPh (76 mg, 0.25 mmol) and benzyl
and then cooled to room temperature. The resulting mixture alcohol (68 mg, 0.625 mmol) were added into the Schlenk
was concentrated to dryness under reduced pressure and the tube. The mixture was stirred at 140 °C for 24 h, cooled to
residue was purified by column chromatography on silica gel room temperature, and concentrated to dryness under reduced
to give 3a (1.14 g, 80%).
pressure. The residue was purified by column chromatography
on silica gel to give phenethyldiphenyl phosphine oxide (3a) in
87% yield.
17
Reduction of Ph2P(O)CH2CH2Ph (3a) with HSiCl3
A Schlenk tube was charged with 3a (0.05 mmol), HSiCl3
Reaction of PhCH2OH with Ni(COD)2-IMes. IMes·HCl
(0.5 mmol), Et3N (1.0 mmol) and toluene (2.0 cm3) under a (682 mg, 2 mmol), t-BuOK (224 mg, 2 mmol) and CPME
nitrogen atmosphere. The solution was stirred at 100 °C for (3 cm3) were successively charged into a Schlenk tube. After
6 h until compound 3a was completely consumed as indicated the mixture was stirred at room temperature for 30 min, Ni
by TLC. Then, NaOH (1.0 mol L−1) was added. The resulting (COD)2 (275 mg, 1 mmol) was added. The resulting mixture
mixture was extracted with EtOAc (3 × 10 cm3). The organic was stirred for 30 min and the color of the solution changed to
phases were washed with brine, dried with anhydrous Na2SO4 dark red. Then PhCH2OH (108 mg, 1 mmol) was added and
and condensed under reduced pressure. The residue was puri- the mixture was further stirred at room temperature for
fied by flash column chromatography to produce 30 min. A small amount of the extract was taken out for
Ph2PCH2CH2Ph26 as a colorless oil (12 mg, 83%). 1H NMR GC-MS analysis. The remaining mixture was filtered under a
(400 MHz, CDCl3): δ 7.50–7.39 (m, 4H), 7.38–7.29 (m, 6H), N2 atmosphere. The solvent was removed from the filtrate in
7.28–7.21 (m, 2H), 7.20–7.12 (m, 3H), 2.77–2.65 (m, 2H), vacuo. The residue was dissolved in C6D6 to record its 1H NMR
2.42–2.31 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 142.73 (d, J = spectrum. No Ni–H signals were observed (until −45 ppm).
13.4 Hz), 138.56 (d, J = 12.7 Hz), 132.87 (d, J = 18.4 Hz), 128.76,
Reaction of Ph2P(O)Me with PhCD2OH
128.63, 128.56, 128.27, 126.14, 32.29 (d, J = 17.8 Hz), 30.32 (d, J
= 12.7 Hz). 31P NMR (162 MHz, CDCl3): δ −15.87.
Preparation of PhCD2OH.28 To a stirred suspension of
NaBD4 (0.55 g, 13 mmol) in dry THF (15 cm3) was added drop-
wise a THF solution (20 cm3) of benzoyl chloride (3 g,
Mechanistic experiments
Reaction of Ph2P(O)Me with PhCHO. Methyldiphenyl- 21 mmol) at 0 °C. The resulting mixture was refluxed for 2 h,
phosphine oxide (54 mg, 0.25 mmol), t-BuOK (34 mg, then cooled to 0 °C, and quenched by dropwise addition of
2240 | Org. Biomol. Chem., 2021, 19, 2233–2242
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THF/H2O (5 cm3, 1 : 1 v/v). The mixture was acidified with 1 M
aqueous HCl (100 cm3) and extracted with Et2O (3 × 20 cm3).
The combined organic layer was dried over anhydrous Na2SO4,
and purified by column chromatography on silica gel to give
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L. C. Morrill, ACS Catal., 2018, 8, 6440; (g) S. Chakraborty,
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1
PhCD2OH in 62% yield (93% D). H NMR (400 MHz, CDCl3): δ
7.39–7.24 (m, 5H), 4.62–4.56 (m, 0.14H), 3.02 (b, 1H).
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Reaction of Ph2P(O)Me with PhCD2OH. Methyldiphenyl-
phosphine oxide (54 mg, 0.25 mmol), Ni(COD)2 (6.9 mg,
0.025 mmol), IMes·HCl (17 mg, 0.05 mmol), t-BuOK (34 mg,
0.30 mmol), PhCD2OH (69 mg, 0.625 mmol), and CPME
(1 cm3) were successively charged into a Schlenk tube. The
mixture was stirred at 140 °C for 24 h, cooled to room tempera-
ture, and concentrated to dryness under reduced pressure. The
residue was purified by column chromatography on silica gel
to give the product in 76% yield. 1H NMR (400 MHz, CDCl3): δ
7.83–7.72 (m, 4H), 7.57–7.43 (m, 6H), 7.26 (t, J = 7.2 Hz, 2H),
7.21–7.13 (m, 3H), 2.99–2.85 (m, 0.89H), 2.64–2.51 (m, 1.64H).
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Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We acknowledge the financial support from the National
Natural Science Foundation of China (Grant No. 21772186).
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