Phosphinoyl radical-initiated vicinal hydroxy-phosphorylation of alkenes

Article abstract of DOI:10.1016/j.tet.2019.130683

A protocol of Mn(OAc)₃–mediated α,β-hydroxy-phosphorylation of alkenes with phosphorus-centered radicals generated from diphenylphosphine oxide is described. A combination of steric and electronic factors played an important role in this reacti

Full text of DOI:10.1016/j.tet.2019.130683

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Phosphinoyl radical-initiated vicinal hydroxy-phosphorylation of alkenes
Adedamola Shoberu, Shuai-Shuai Li, Guo-Yu Zhang, Da-Peng Li, Jian-Ping Zou
PII:
S0040-4020(19)31058-0
https://doi.org/10.1016/j.tet.2019.130683
TET 130683
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 August 2019
Revised Date: 28 September 2019
Accepted Date: 8 October 2019
Please cite this article as: Shoberu A, Li S-S, Zhang G-Y, Li D-P, Zou J-P, Phosphinoyl radical-
initiated vicinal hydroxy-phosphorylation of alkenes, Tetrahedron (2019), doi: https://doi.org/10.1016/
j.tet.2019.130683.
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Phosphinoyl Radical-Initiated Vicinal Hydroxy-
Phosphorylation of Alkenes
Leave this area blank for abstract info.
Adedamola Shoberu, Shuai-Shuai Li, Guo-Yu Zhang, Da-Peng Li, Jian-Ping Zou*
,
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical
Engineering, Soochow University, 199 Renai Street, Suzhou, Jiangsu 215123, China.

1
Tetrahedron
journal homepage: www.elsevier.com
Phosphinoyl Radical-Initiated Vicinal Hydroxy-Phosphorylation of Alkenes
Adedamola Shoberu, Shuai-Shuai Li, Guo-Yu Zhang, Da-Peng Li, Jian-Ping Zou*
,
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical Engineering, Soochow University, 199 Renai Street, Suzhou,
Jiangsu 215123, China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
3
A protocol of Mn(OAc) –mediated α,β-hydroxy-phosphorylation of alkenes with phosphorus-
centered radicals generated from diphenylphosphine oxide is described. A combination of steric
and electronic factors played an important role in this reaction. The reactions of styrenes bearing
ortho-substituent gave the selective β-hydroxyphosphine oxide products.
Available online
2
017 Elsevier Ltd. All rights reserved.
Keywords:
Keyword_1 manganese(III) acetate
Keyword_2 styrenes
Keyword_3 difunctionalization reaction
Keyword_4 phosphorus-centered radical reaction
1
. Introduction
Recently, our group disclosed the Mn(III)-mediated direct
11
radical acetoxy-phosphorylation of styrenes and afterwards, the
direct radical oxy-phosphorylation of styrenes with
The difunctionalization of alkenes is a reaction of considerable
interest in organic synthesis since they provide rapid access to
many important and fascinating organic compounds. This kind
of reactions are known for their efficiency as well as considerable
atom and step economy. In particular, those that feature the
incorporation phosphorus-containing functionalities are attractive
since the resultant product serve not only as key intermediates in
the well-known Horner-Wittig reaction, but also as versatile
building blocks for the synthesis of various useful compounds in
organic chemistry.
1
diarylphosphine oxides and dialkyl phosphites (Scheme 1a and
12
1
b). Although the choice of solvent played a major role in
determining the identity of products obtained from these
reactions, hydroxy-phosphorylated were obtained as side
products in some cases. Inspired by this observation, we decided
to study the reactions further in a bid to achieve the selective
synthesis of β-hydroxyphosphorylated compounds (Scheme 1c).
2
3
β-Hydroxyphosphonates are regarded as valuable compounds
due to their potential utility in the synthesis of herbicides,
horticulture 4 agents, antioxidants, and moisture-resistant
compounds. They are also considered as bioisosteres of
5
carboxylic acids with potential biological properties. The
hydroxy group present in this class of compounds could be
further transformed into a variety of other functional groups such
as esters, amines, phenyl ethers etc. Generally, β-
hydroxyphosphonates can be prepared from the hydrogenation of
6
β-ketophosphonates, or the ring-opening reaction of epoxy
7
compounds with phosphorus nucleophiles. Other methods
include the nucleophilic addition of the anions8 of
alkyl(diphenyl)phosphine oxides to carbonyl compounds, the
nucleophilic addition of organolithium reagents to β-
Scheme 1. Mn(III)-mediated acetoxy-phosphorylation and oxy-
9
phosphorylation of styrenes
ketophosphine oxides, or the oxidation of β-hydroxyphosphines
10
with H O .
However, most of these methods suffer from
2
2
drawbacks such as poor functional group tolerance, use of
hazardous reagents, and low atom economy.

2
Tetrahedron
below.
2
. Results and Discussion
After careful consideration of previous reactions, it was
Other electron-donating groups at the ortho-position of styrene
didn’t fear well. 2-Methoxystyrene resulted in a mixture of β-
hydroxy- and β-oxy-phosphorylated products (3b and 3bʹ). The
expected product 3c was not detected in the case of 2-
aminostyrene. Meanwhile, substrates containing ortho-
substituted electron-withdrawing groups gave satisfactory yields
of the corresponding β-hydroxy products. For instance, halo
groups including fluoro, chloro and bromo groups furnished the
desired compounds in satisfactory yields (3d-g). Strongly
electron-withdrawing groups such as trifluoromethyl and nitro
groups also gave good yields of the desired products (3h and 3i).
Surprisingly, 2-cyanostyrene afforded a mixture of the β-oxy-
and β-hydroxy phosphorylated products in 70% combined yield
discovered that the pattern of substitution as well as electronic
factors had a direct influence on product selectivity. For instance,
sterically hindered alkenes tended to give exclusively, the β-
hydroxy products. This is in contrast to reported procedures
where the presence of β-substituents was necessary to achieve
selective synthesis of β-hydroxyphosphorylated compounds.
This is exemplified by the reaction of 2-methylstyrene with
HP(O)Ph (1.5 equiv) which was carried out in the presence of
13
2
o
Mn(OAc) (2 equiv) in MeOH at 30 C for 1 hour. This resulted
3
in the formation of the corresponding (2-hydroxy-2-(o-tolyl)ethyl)
diphenylphosphine oxide in 72% yield (Table 1, 3a). No further
optimization was deemed necessary at this stage. Based on this
positive result, the reactions of other sterically demanding
substrates were carried out and the results are shown in Table 1
(3j). An acetamido group on styrene also furnished product 3k in
a moderate 45% yield, while no expected product 3c was formed
with free ortho-amino group on styrene, this finding indicated
that both sterical and electronic factors played important role for
hydroxy-phosphorylation of styrene at the same time (also see 3h
vs 3v, 3i vs 3w). Unfortunately, the presence of a 2-phenyl
substituent inhibited the reaction, and only a trace amount of
product was observed (3l); Again, 1-naphthyl group led to a
mixture of β-oxy- and β-hydroxy products (3m and 3mʹ), this
observation showed that suitable sterical and electronic effect is
Table 1. Reactions of alkenes 1 with diphenylphosphine
a
oxide 2
crucial
to
selective
hydroxy-phosphorylation
reaction.
Unsurprisingly, the substrates bearing β-methyl and β-phenyl
provided the desired β-hydroxy products in 73% and 74% yields,
respectively (3n and 1 3o) due to no competitive oxy-
2, 13
phosphorylation reaction.
Interestingly, substrates bearing α-
methyl and α-phenyl also produced the selective β-hydroxy
products in 73% and 65% yields, respectively (3p and 3q), this
provided a direct approach for synthesis of α-substituted-α-
12
phosphorylated-β-hydroxy compounds.
Surprisingly, indene
was not viable substrate for this reaction (3r). Furthermore, the
reactions of heteroaryl alkenes were examined; with the
exception of the 2-thiophenyl- (3s, 50%), 2-pyrrolyl- and 2-
pyridyl-containing alkenes were not suitable substrates under the
reaction conditions (3t and 3u). As shown in Table 1, styrenes
bearing ortho-strong electron-withdrawing groups such as CF3
and NO gave satisfactory yields of the corresponding β-hydroxy
2
products 3h and 3i (67 and 71%, respectively). On the contrast,
styrenes bearing meta-CF3 and para-NO2 groups gave the
expected products 3v and 3w in very low yields (10 and 25%,
respectively), these results revealed that the combination of
sterical hindered and electron-withdrawing effect of groups could
lead to the selective hydroxy-phosphorylation of styrenes.
Moreover, the reactions of substituted diphenylphosphine oxides
such as bis(4-methoxyphenyl)phosphine oxide and bis(4-
chlorophenyl)phosphine oxide with ortho-chlorostyrene were
also carried out, the former gave the expected β-
hydroxyphosphorylated product 3x in 61% yield; but the latter
gave the methyl bis(4-chlorophenyl)phosphinate in 51% yield,
which generated from the reaction of bis(4-chlorophenyl)
phosphoryl radical with methanol, whereas the expected β-
hydroxyphosphorylated product 3y was not observed (see
supporting information). It is worth mentioning that using
dimethylphosphite instead of diphenylphosphine oxide gave the
corresponding β-oxyphosphorylated products 4a and 4b (Table 2),
not β-hydroxyphosphorylated products 3 under the present
protocol.
a
Reaction conditions: Alkene (1 mmol), HP(O)Ph
2
(2 mmol),
o
b
Although the role played by steric and electronic factors in
influencing product selectivity remains unclear at this stage, a
plausible mechanism was proposed based on results obtained and
3 3
Mn(OAc) (2 mmol) in CH OH (5 mL) at 30 C for 1 h. N.D. means
not detected. Inseparable mixture of oxy-phosphorylation and
hydroxy-phosphorylation products.
c
11,12,14,15
III
previous studies (Scheme 2).
Mn
interacts with
diphenylphosphine oxide 2 to generate the phosphorus-centered

3
radical A which then attacks the C═C double bond of alkene 1 to
To
a
stirring solution of alkene (1.0 mmol) and
o
14a,15
furnish benzylic radical B.
This is trapped by molecular
diphenylphosphine oxide (2.0 mmol) in MeOH (5 mL) at 30 C
oxygen from air to afford the peroxy radical C which could
was added Mn(OAc) (2.0 mmol) in portions over 30 minutes.
3
14b
combine further with B to give the peroxide D. Subsequent
homolytic cleavage of D will afford the alkoxy radical E which is
subsequently reduced by diphenylphosphine oxide 2 to give the
After the completion of reaction as indicated by TLC (about 30
minutes later), the mixture was cooled and the solvent was
removed under vacuum. The pure product 3 was obtained by
column chromatography on silica gel using petroleum
ether/EtOAc/CH Cl (4:1:1) as eluent.
14b,c
observed product 3.
2
2
Table 2. Reactions of ortho-substituted styrenes 1 with
a,b
dimethylphosphite
4.3 Characterization
(2-Hydroxy-2-(o-tolyl)ethyl)diphenylphosphine oxide (3a)
o
1
White solid; m.p. 189-190 C, 72% yield (242.0 mg). H NMR
(
600 MHz, CDCl ): δ 7.78-7.88 (m, 2H), 7.70-7.76 (m, 2H), 7.56-
3
7
.64 (m, 2H), 7.50-7.55 (m, 3H), 7.44-7.49 (m, 2H), 7.22 (t, J = 7.5
Hz, 1H), 7.13 (t, J = 7.4 Hz, 1H), 7.04 (d, J = 7.5 Hz, 1H), 5.28-5.38
(
m, 1 H), 4.01 (s, 1 H), 2.66-2.76 (m, 1H), 2.45-2.55 (m, 1H), 2.01
13
(s, 3H); C NMR (150 MHz, CDCl ): δ 141.8 (d, J = 13.0 Hz),
3
1
1
33.4, 132.3, 131.0 (d, J = 9.2 Hz), 130.4 (d, J = 9.5 Hz), 130.3,
28.8 (d, J = 19.5 Hz), 127.4, 126.5, 125.3, 65.5, 37.9 (d, J = 67.8
a
Reaction conditions: Styrene (1 mmol), HP(O)(OMe)
2
(2 mmol), Mn(OAc)
3
31
Hz), 18.6; P NMR (162 MHz, CDCl ): δ 34.1. HRMS (ESI-TOF)
m/z: (M+H) Calcd for C H O P 337.1357, found 337.1375.
3
o
b
(
2 mmol) in CH
3
OH (5 mL) at 30 C for 1 h. Isolated yield.
+
21
22
2
(2-Hydroxy-2-(2-methoxyphenyl)ethyl)diphenylphosphine oxide (3b)
o
1
White solid; m.p. 175-177 C, 30% yield (78.8 mg). H NMR
(
400 MHz, CDCl ): δ 7.92–7.83 (m, 2H), 7.68–7.59 (m, 3H), 7.59–
3
7
8
.50 (m, 3H), 7.48–7.39 (m, 3H), 7.19 (t, J = 8.0, 1H), 6.96 (t, J =
.0, 1H), 6.76 (d, J = 8.0, 1H), 5.53–7.31 (m, 1H), 4.94 (s, 1H), 3.71
13
(s, 3H), 2.94–2.81 (m, 1H), 2.66–2.44 (m, 1H); C NMR (100 MHz,
CDCl ): δ 155.0, 133.3 (d, J = 99.0 Hz), 131.9 (d, J = 13.0 Hz),
3
1
1
1
31.9 (d, J = 2.0 Hz), 131.8 (d, J = 98.0 Hz), 131.8 (d, J = 3.0 Hz),
31.0 (d, J = 9.0 Hz), 130.8 (d, J = 10.0 Hz), 130.2 (d, J = 10.0 Hz),
28.5 (d, J = 12.0 Hz), 128.1, 125.8, 120.8, 109.8, 64.4 (d, J = 5.0
31
Scheme 2. Proposed mechanism
Hz), 55.0, 36.8 (d, J = 69.0 Hz); P NMR (162 MHz, CDCl ): δ
3
3
3
+
4.7. HRMS (ESI-TOF) m/z: (M+H) Calcd for C H O P
21 22 3
53.1307, found 353.1301.
3
. Conclusion
2
-(Diphenylphosphoryl)-1-(2-methoxyphenyl)ethanone (3bʹ)
In summary,
a
new protocol of Mn(OAc) -mediated
o
1
3
White solid; m.p. 141–142 C, 50% yield (174.4 mg). H NMR
400 MHz, CDCl ): δ 7.78–7.72 (m, 4H), 7.52–7.45 (m, 3H), 7.44–
hydroxyphosphorylation of styrenes in air has been developed. A
combination of steric and electronic factors played an important
role in this reaction. Thus, β-hydroxyphosphorylated compounds
were selectively formed in moderate to good yields. Ortho-
electron-withdrawing groups substituted styrenes tended to
favour the formation of the desired products. Advantages of this
methodology include mild reaction conditions, simple
manipulations and the use of molecular oxygen as O-atom source.
(
3
7
1
6
1
1
2
3
.30 (m, 5H), 6.89 (t, J = 8.0, 1H), 6.80 (d, J = 8.0, 1H), 4.37 (d, J =
6.0, 2H), 3.79 (s, 3H); C NMR (100 MHz, CDCl ): δ 194.1 (d, J =
.0 Hz), 158.4, 134.2, 132.7 (d, J = 102.0 Hz), 131.8 (d, J = 2.0 Hz),
31.2 (d, J = 10.0 Hz), 130.7, 128.4 (d, J = 12.0 Hz), 128.0, 120.6,
11.3, 65.4, 47.1 (d, J = 57.0 Hz); P NMR (162 MHz, CDCl ): δ
3.5. HRMS (ESI-TOF) m/z: (M+H) Calcd for C H O P
13
3
31
3
+
2
1
20
3
51.1150, found 351.1135.
4
4
. Experimental Section
(
2-(2-Fluorophenyl)-2-hydroxyethyl)diphenylphosphine oxide (3d)
.1. General
o
1
White solid; m.p. 177-178 C, 74% yield (251.6 mg). H NMR
(400 MHz, CDCl ): δ 7.84-7.93 (m, 2H), 7.65-7.74 (m, 3H), 7.54-
1
13
H NMR (400 MHz or 300 MHz) and C NMR (150, 100 or 75
3
MHz) spectra were determined with CDCl or DMSO-d as solvent
7.64 (m, 3H), 7.49-7.53 (m, 1H), 7.42-7.48 (m, 2H), 7.12-7.25 (m,
3
6
and tetramethylsilane (TMS) as internal standard or 85% H PO as
2H), 6.90-6.98 (m, 1H), 5.42-5.53 (m, 1H), 5.25 (d, J = 1.8 Hz, 1H),
3
4
31
13
external standard for P NMR (162 MHz). Chemical shifts were
reported in ppm from internal TMS (δ), all coupling constants (J
values) were reported in Hertz (Hz). High resolution mass spectra
were recorded on a TOF machine (ESI). Column chromatography
was performed with 300-400 mesh silica gel using flash column
techniques. All of the reagents were used directly as obtained
commercially unless otherwise noted. All alkenes were purified by
flash column chromatography (Al O ) before use.
2.76-2.85 (m, 1H), 2.62-2.74 (m, 1H); C NMR (100 MHz, CDCl
):
3
δ 159.0 (d, J = 243.3 Hz), 135.1 (d, J = 9.3 Hz), 132.3 (d, J = 2.7
Hz), 132.1 (d, J = 6.6 Hz), 130.3 (d, J = 9.9 Hz), 128.6 (d, J = 1.7
Hz), 127.1 (d, J = 4.2 Hz), 124.4 (d, J = 3.4 Hz), 116.6 (d, J = 23.7
3
1
Hz), 114.8 (d, J = 21.1 Hz), 63.8, 37.3 (d, J = 68.2 Hz); P NMR
+
(162 MHz, CDCl
): δ. 34.7. HRMS (ESI-TOF) m/z: (M+H) Calcd
3
for C20 P 341.1107, found 341.1095.
H19FO
2
2
3
(2-(2-Chlorophenyl)-2-hydroxyethyl)diphenylphosphine oxide (3e)
4
.2. General procedure for the preparation of β-hydroxy-
o
1
White solid; m.p. 171-172 C, 68% yield (242.1 mg). H NMR
phosphine oxides 3
(
400 MHz, CDCl ): δ 7.85-7.95 (m, 2H), 7.76-7.85 (m, 1H), 7.67-
3

4
Tetrahedron
7
.75 (m, 2H), 7.42-7.64 (m, 6H), 7.26-7.35 (m, 2H), 7.14-7.23 (m,
2H), 7.68–7.62 (m, 1H), 7.60–7.56 (m, 2H), 7.53–7.50 (m, 2H),
1
H), 5.40-5.52 (m, 1H), 4.74 (s, 1H), 2.76-2.88 (m, 1H), 2.46-2.64
7.48–7.44 (m, 5H), 7.36–7.32 (m, 1H), 5.95–5.72 (m, 1H), 3.77 (d, J
13
(m, 1H); C NMR (100 MHz, CDCl ): δ 141.3 (d, J = 13.4 Hz),
= 12.0 Hz, 0.7H (C(O)CH )), 3.06–2.96 (m, 1H), 2.91–2.79 (m, 1H);
3
2
13
1
32.3 (d, J = 14.8 Hz), 131.2 (d, J = 9.5 Hz), 130.6, 130.3 (d, J = 9.8
C NMR (100 MHz, CDCl ): δ 173.47, 169.17, 148.98, 136.82,
3
Hz), 129.1, 128.8 (d, J = 4.0 Hz), 128.7 (d, J = 4.0 Hz), 128.5, 127.3
135.83, 133.96, 131.95 (d, J = 3.0 Hz), 131.77 (d, J = 9.0 Hz),
131.22, 131.14, 130.93, 130.82, 130.78, 130.73, 130.63, 130.08,
129.98, 129.00, 128.55, 128.50, 128.43, 128.38, 128.19, 128.06,
127.81 (d, J = 13.0 Hz), 125.07, 124.95, 122.82, 120.89, 118.35,
31
(
d, J = 9.3 Hz), 66.3, 36.8 (d, J = 67.7 Hz); P NMR (162 MHz,
+
CDCl ): δ 34.9. HRMS (ESI-TOF) m/z: (M+H) Calcd for
3
C H ClO P 357.0811, found 357.0820.
20
19
2
7
5.17, 51.00, 35.99 (d, J = 20.0 Hz), 28.80, 13.89. HRMS (ESI-TOF)
(
2-(2,6-Dichlorophenyl)-2-hydroxyethyl)diphenylphosphine
oxide
+
m/z: (M+H) Calcd for C H NO P 348.1153, found 348.1143.
HRMS (ESI-TOF) m/z: (M+H) Calcd for C H NO P 346.0997,
found 346.0985.
21
19
+
2
(3f)
21
17
2
o
1
White solid; m.p. 175-176 C, 70% yield (273.0 mg). H NMR
(
7
400 MHz, CDCl ): δ 7.75-7.90 (m, 4H), 7.45-7.65 (m, 6H), 7.26-
.33 (m, 2H), 7.05-7.15 (m, 1H), 5.92-6.02 (m, 1H), 4.51 (d, J = 3.9
3
N-(2-(2-(Diphenylphosphoryl)-1-hydroxyethyl)phenyl)acetamide
(3k)
Hz, 1H), 3.40-3.52 (m, 1 H), 2.59 (ddd, J = 2.8, 8.2, 15.0 Hz, 1H);
1
3
o
1
C NMR (100 MHz, CDCl ): δ 136.6 (d, J = 12.6 Hz), 134.6, 132.1
White solid; m.p. 196−197 C, 45% yield (170.6 mg). H NMR
3
(d, J = 68.2 Hz), 131.1 (d, J = 9.5 Hz), 130.5 (d, J = 9.8 Hz), 129.5,
(400 MHz, CDCl ): δ 9.51 (s, 1H), 7.97 (d, J = 7.7 Hz, 1H), 7.62–
3
1
29.2, 128.8 (d, J = 3.4 Hz), 128.7 (d, J = 3.2 Hz), 66.7 (d, J = 3.0
7.81 (m, 4H), 7.60–7.42 (m, 6H), 7.25–7.18 (m, 1H), 7.11–6.91 (m,
31
Hz), 34.3 (d, J = 68.2 Hz); P NMR (162 MHz, CDCl ): δ 33.1.
HRMS (ESI-TOF) m/z: (M+H) Calcd for C H Cl O P 391.0421,
2H), 5.41 (s, 1H), 5.28 (t, J = 8.7 Hz, 1H), 3.10–2.93 (m, 1H), 2.72–
3
+
13
2.52 (m, 1H), 2.13 (s, 3H); C NMR (101 MHz, CDCl ): δ 168.3,
20
18
2
2
3
found 391.0453.
135.8, 131.9 (d, J = 2.4 Hz), 131.8 (d, J = 2.5 Hz), 130.3 (d, J = 9.5
Hz), 129.8 (d, J = 9.9 Hz), 128.5 (d, J = 3.5 Hz), 128.4 (d, J = 3.3
(2-(2-Bromophenyl)-2-hydroxyethyl)diphenylphosphine oxide (3g)
Hz), 128.1, 126.1, 124.0 , 123.2, 68.8, 36.1 (d, J = 68.4 Hz), 24.2;
o
1
31
White solid; m.p. 170-171 C, 50% yield (200.0 mg). H NMR
P NMR (162 MHz, CDCl
3
): δ 34.5. HRMS (ESI-TOF) m/z:
H13NO P 380.1416, found 380.1423.
3
+
(400 MHz, CDCl ): δ 7.83-7.96 (m, 2H), 7.77 (d, J = 7.8 Hz, 1H),
(M+H) Calcd for C22
3
7
.65-7.73 (m, 2H), 7.48-7.63 (m, 4H), 7.38-7.48 (m, 3H), 7.29-7.35
(
2-Hydroxy-2-(naphthalen-1-yl)ethyl)diphenylphosphine oxide (3m)
(m, 1H), 7.08 (td, J = 1.6, 7.7 Hz, 1H), 5.45 (s, 1H), 5.37 (t, J = 10.1
o
1
Hz, 1H), 2.81 (ddd, J = 1.6, 6.6, 14.9 Hz, 1H), 2.42-2.56 (m, 1H);
White solid; m.p. 174−175 C, 35% yield (130.3 mg). H NMR
13
C NMR (100 MHz, CDCl ): δ 142.8 (d, J = 13.7 Hz), 132.4, 132.3
(400 MHz, CDCl ): δ 7.89–7.80 (m, 4H), 7.73–7.53 (m, 6H), 7.49–
3
3
(
d, J = 2.8 Hz), 132.2 (d, J = 2.8 Hz), 131.3 (d, J = 9.6 Hz), 130.4 (d,
7.34 (m, 6H), 7.30 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 5.89 (t, J = 10.0
Hz, 1H), 5.24 (s, 1H), 2.87–2.71 (m, 1H); C NMR (101 MHz,
13
J = 9.8 Hz), 128.9, 128.8 (d, J = 7.7 Hz), 127.8 (d, J = 34.5 Hz),
1
MHz, CDCl ): δ. 34.8. HRMS (ESI-TOF) m/z: (M+H) Calcd for
C H BrO P 401.0306, found 401.0313.
31
20.7, 68.5 (d, J = 4.1 Hz), 37.0 (d, J = 67.4 Hz); P NMR (162
CDCl ): δ 138.8 (d, J = 13.1 Hz), 133.2, 131.8 (d, J = 2.8 Hz), 131.7
3
+
(d, J = 2.7 Hz), 130.7 (d, J = 9.5 Hz), 129.9 (d, J = 9.8 Hz), 129.0,
128.5 (d, J = 6.3 Hz), 128.4 (d, J = 7.7 Hz), 128.2, 127.5, 125.4 (d, J
3
20
19
2
=
26.7 Hz), 124.9, 122.1 (d, J = 69.6 Hz), 65.3 (d, J = 4.2 Hz), 38.1
(
2-Hydroxy-2-(2-(trifluoromethyl)phenyl)ethyl)diphenylphosphine
31
(d, J = 68.3 Hz); P NMR (162 MHz, CDCl ): δ 33.8. HRMS (ESI-
3
oxide (3h)
+
TOF) m/z: (M+H) Calcd for C H O P 373.1357, found 373.1361.
24
22
2
o
1
White solid; m.p. 185-186 C, 67% yield (261.4 mg). H NMR
2
-(Diphenylphosphoryl)-1-(naphthalen-1-yl)ethanone (3mʹ)
(
400 MHz, CDCl ): δ 8.01 (d, J = 7.8 Hz, 1H), 7.80-7.89 (m, 2H),
3
o
1
7
(
.70-7.78 (m, 2H), 7.54-7.66 (m, 6H), 7.46-7.52 (m, 2H), 7.33-7.41
m, 1H), 5.52-5.58 (m, 1H), 5.51 (s, 1H), 2.57-2.63 (m, 1H), 1.65-
White solid; m.p. 182−183 C, 30% yield (111.1 mg). H NMR
(400 MHz, CDCl ): δ 8.43 (dq, J = 6.7, 3.2 Hz, 1H), 8.17 (dd, J = 7.2,
0.8 Hz, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.85–7.75 (m, 5H), 7.53–7.46
(m, 5H), 7.46–7.39 (m, 4H), 4.28 (d, J = 15.2 Hz, 2H); C NMR
(101 MHz, CDCl ): δ 195.1 (d, J = 5.7 Hz), 134.7, 133.3, 133.2,
131.6 (d, J = 2.7 Hz), 130.7, 130.6, 129.8, 129.6, 128.2, 128.1, 127.8
(d, J = 21.9 Hz), 126.0, 125.2, 123.9, 46.0 (d, J = 57.9 Hz); P NMR
(162 MHz, CDCl ): δ 27.3. HRMS (ESI-TOF) m/z: (M+H) Calcd
3
13
1
1
3
1
.73 (m,1H); C NMR (100 MHz, CDCl ): δ 132.5, 132.3 (d, J =
3
1
3
0.0 Hz), 131.2 (d, J = 9.5 Hz), 130.3 (d, J = 9.3 Hz), 128.9 (d, J =
.1 Hz), 128.7 (d, J = 3.2 Hz), 127.9, 127.6, 125.6 (d, J = 24.5 Hz),
3
31
25.3 (q, J = 5.8 Hz), 122.7, 65.0, 39.2 (d, J = 77.3 Hz); P NMR
+
31
(162 MHz, CDCl ): δ 33.5. HRMS (ESI-TOF) m/z: (M+H) Calcd
3
+
for C H F O P 391.1075, found 391.1083.
21
19
3
2
3
for C H O P 371.1201, found 371.1197.
24
20
2
(2-Hydroxy-2-(2-nitrophenyl)ethyl)diphenylphosphine oxide (3i)
1
6
(
2-Hydroxy-2-phenylpropyl)diphenylphosphine oxide (3n)
o
1
White solid; m.p. 165−166 C, 71% yield (260.8 mg). H NMR
o
1
(
400 MHz, CDCl ): δ 8.08 (d, J = 7.5 Hz, 1H), 7.96–7.86 (m, 3H),
White solid; m.p. 178-179 C, 73% yield (245.4 mg). H NMR
3
7
(
3
.73–7.64 (m, 3H), 7.63–7.55 (m, 3H), 7.54–7.49 (m, 1H), 7.47–7.41
m, 2H), 7.41–7.35 (m, 1H), 5.79 (s, 1H), 5.64 (t, J = 9.9 Hz, 1H),
.00 (ddd, J = 14.9, 6.9, 1.8 Hz, 1H), 2.59 (ddd, J = 14.9, 12.1, 10.3
(400 MHz, CDCl ): δ 7.73-7.82 (m, 2H), 7.48-7.57 (m, 3H), 7.32-
3
7.40 (m, 5H), 7.20-7.25 (m, 2H), 7.01-7.15 (m, 3H), 5.07 (s, 1H),
13
2.94 (d, J = 9.6 Hz, 1H), 1.62 (s, 3H); C NMR (100 MHz, CDCl3):
δ 146.7 (d, J = 5.8 Hz), 131.9 (d, J = 2.5 Hz), 131.2 (d, J = 2.8 Hz),
130.3 (d, J = 9.6 Hz), 128.8 (d, J = 11.8 Hz), 128.2 (d, J = 12.0 Hz),
127.8, 126.6, 124.8, 74.2 (d, J = 5.3 Hz), 42.3 (d, J = 68.6 Hz), 32.8
13
Hz, 1H); C NMR (101 MHz, CDCl ): δ 146.2, 139.3 (d, J = 14.2
Hz), 133.6, 130.8 (d, J = 9.7 Hz), 129.8 (d, J = 9.8 Hz), 128.5 (d, J =
1
Hz), 37.3 (d, J = 67.6 Hz); P NMR (162 MHz, CDCl ): δ 35.1.
HRMS (ESI-TOF) m/z: (M+H) Calcd for C H NO P 368.1052,
3
0.2 Hz), 128.4, 128.2 (d, J = 16.0 Hz), 127.8, 123.8, 65.1 (d, J = 4.0
31
+
(d, J = 9.5 Hz). MS (ESI-TOF) m/z: (M+H) Calcd for C H O P
3
21 22
2
+
337.1, found 337.1.
20
19
4
found 368.1045.
1
6
(2-Hydroxy-2,2-diphenylethyl)diphenylphosphine oxide (3o)
Mixture of 2-(2-(diphenylphosphoryl)-1-hydroxyethyl)benzonitrile
o
1
White solid; m.p. 183-184 C, 74% yield (294.6 mg). H NMR
(3j) and 2-(2-(diphenylphosphoryl)acetyl)benzonitrile (3j’)
(
400 MHz, CDCl ): δ 7.47-7.54 (m, 4H), 7.40-7.45 (m, 2H), 7.30-
7.37 (m, 8H), 7.02-7.12 (m, 6H), 4.50 (s, 1H), 3.40 (d, J = 9.6 Hz,
1H); C NMR (100 MHz, CDCl ): δ 145.2 (d, J = 7.2 Hz), 133.1 (d,
3
3
1
White solid; 70% yield (243.6 mg). H NMR (400 MHz, CDCl ):
3
13
δ 9.29 (s, 1H), 7.90–7.87 (m, 3H), 7.86–7.79 (m, 3H), 7.77–7.71 (m,

5
3
1
J = 100.0 Hz), 131.6 (d, J = 2.7 Hz), 130.4 (d, J = 7.5 Hz), 128.8 (d,
J = 12.0 Hz), 126.4, 123.7, 68.6, 39.0 (d, J = 67.9 Hz); P NMR
+
J = 11.8 Hz), 128.5 (d, J = 12.0 Hz), 127.9, 126.9, 125.9, 77.7 (d, J =
(162 MHz, CDCl ): δ 33.8. HRMS (ESI-TOF) m/z: (M+H) Calcd
3
+
4
.9 Hz), 40.9 (d, J = 69.0 Hz). MS (ESI-TOF) m/z: (M+H) Calcd
for C H NO P 368.1052, found 368.1061.
20
19
4
for C H O P 399.1, found 399.1.
26
24
2
19
2
-(Diphenylphosphoryl)-1-(4-nitrophenyl)ethanone (3wʹ)
17
(1-Hydroxy-1-phenylpropan-2-yl)diphenylphosphine oxide (3p)
o
1
Yellow solid; m.p. 163-164 C, 30% yield (109.0 mg). H NMR
(400 MHz, CDCl ): δ 8.26 (d, J = 8.9 Hz, 2H), 8.20 (d, J = 8.9 Hz,
o
1
White solid; m.p. 189-190 C, 70% yield (235.3 mg). H NMR
3
(
7
7
400 MHz, CDCl ): δ 7.70-7.80 (m, 2H), 7.28-7.40 (m, 4H), 6.98-
2H), 7.76-7.83 (m, 4H), 7.54-7.59 (m, 2H), 7.46-7.53 (m, 4H), 4.17
3
13
.24 (m, 9H), 4.54-4.70 (m, 1H), 2.90-3.05 (m, 1H), 1.05 (dd, J =
(d, J = 15.1 Hz); C NMR (100 MHz, CDCl ): δ 191.6 (d, J = 5.8
3
13
.2, 16.8 Hz, 3H); C NMR (100 MHz, CDCl ): δ 139.3 (d, J = 4.2
Hz), 150.5, 141.2, 132.5 (d, J = 2.9 Hz), 131.9, 131.0 (d, J = 9.8 Hz),
3
3
1
Hz), 135.5 (d, J = 96.8 Hz), 132.2 (d, J = 8.3 Hz), 130.7 (d, J = 4.2
Hz), 130.6, 128.6 (d, J = 11.3 Hz), 128.1 (d, J = 11.0 Hz), 127.9,
130.4, 128.8 (d, J = 12.4 Hz), 123.7, 44.3 (d, J = 54.8 Hz). P NMR
+
(162 MHz, CDCl ): δ 26.55; MS (ESI-TOF) m/z: (M+H) Calcd for
3
1
27.5 (d, J = 11.2 Hz), 126.7, 53.6 (d, J = 3.0 Hz), 37.2 (d, J = 69.5
C H NO P 366.1, found 366.1.
20
19
4
+
Hz), 16.8. MS (ESI-TOF) m/z: (M+H) Calcd for C H O P 337.1,
found 337.1.
21
22
2
(2-(2-Chlorophenyl)-2-hydroxyethyl)bis(4-methoxyphenyl)phosphine
oxide(3x)
18
(2-Hydroxy-1,2-diphenylethyl)diphenylphosphine oxide (3q)
o
1
White solid; m.p. 167-168 C, 61% yield (287.0 mg). H NMR (400
o
1
White solid; m.p. 248-249 C, 65% yield (258.8 mg). H NMR
MHz, CDCl ): δ 7.93-7.6 7(m, 3H), 7.66-7.47 (m, 2H), 7.34-7.19 (m,
2H), 7.19-7.10 (m, 1H), 7.10-6.98 (m, 2H), 6.98-6.86 (m, 2H), 5.69
3
(
7
400 MHz, CDCl ): δ 8.00-8.10 (m, 2H), 7.50-7.69 (m, 5H), 7.18-
3
.36 (m, 5H), 7.04-7.16 (m, 6H), 6.86-6.94 (m, 2 H), 5.54 (d, J = 7.2
(
1
br, OH), 5.51-5.29 (m, 1H), 3.86 (s, 3H), 3.83 (s, 3H), 2.83-2.62 (m,
H), 2.60-2.35 (m, 1H). C NMR (101 MHz, CDCl ): δ 162.83,
3
13
Hz, 1H), 5.20 (s, 1H), 3.67 (d, J = 8.0 Hz, 1H); C NMR (100 MHz,
CDCl ): δ 141.2 (d, J = 12.2 Hz), 132.1 (d, J = 2.4 Hz), 131.9 (d, J =
2
Hz), 130.7 (d, J = 9.1 Hz), 129.1 (d, J = 11.4 Hz), 128.3 (d, J = 12.0
Hz), 127.7, 127.1 (d, J = 12.9 Hz), 125.9, 72.6, 53.2 (d, J = 66.2 Hz).
MS (ESI-TOF) m/z: (M+H) Calcd for C H O P 399.1, found
13
3
162.64, 133.31, 133.24, 132.41, 130.74, 129.18, 128.52, 127.41,
.9 Hz), 131.6 (d, J = 2.5 Hz), 131.3 (d, J = 6.9 Hz), 131.0 (d, J = 8.7
31
1
(
27.38, 114.53, 114.44, 114.34, 66.44, 55.50, 55.46, 29.80. P NMR
+
162 MHz, CDCl ): δ 35.19. HRMS (ESI-TOF) m/z: (M+Na) Calcd
3
for C H ClNaO P 439.0842, found 439.0820.
22
22
4
+
26
24
2
Dimethyl (2-oxo-2-(o-tolyl)ethyl)phosphonate (4a)
3
99.1.
1
Colorless liquid; 66% yield (159.8 mg). H NMR (400 MHz,
Mixture of (2-hydroxy-2-(thiophen-2-yl) ethyl) diphenylphosphine
oxide (3s) and (2-(diphenylphosphoryl)-1-(thiophen-2-yl) ethanone
CDCl ): δ 7.70-7.80 (m, 2H), 7.28-7.40 (m, 4H), 6.98-7.24 (m, 9H),
.54-4.70 (m, 1H), 2.90-3.05 (m, 1H), 1.05 (dd, J = 7.2, 16.8 Hz,
H); C NMR (100 MHz, CDCl ): δ 139.3 (d, J = 4.2 Hz), 135.5 (d,
J = 96.8 Hz), 132.2 (d, J = 8.3 Hz), 130.7 (d, J = 4.2 Hz), 130.6,
28.6 (d, J = 11.3 Hz), 128.1 (d, J = 11.0 Hz), 127.9, 127.5 (d, J =
1.2 Hz), 126.7, 53.6 (d, J = 3.0 Hz ), 37.2 (d, J = 69.5 Hz ), 16.8.
HRMS (ESI-TOF) m/z: (M+H) Calcd for C H O P 243.0786,
3
4
3
(3s’)
13
3
1
White solid; 50% yield (164.8 mg). H NMR (400 MHz, CDCl ):
3
δ 7.93 (d, J = 4.5 Hz, 1H), 7.91–7.82 (m, 5H), 7.80–7.74 (m, 0.84H),
1
1
7
7
.67 (d, J = 4.9 Hz, 1H), 7.66–7.60 (m, 0.84H), 7.60–7.55 (m, 3H),
.55–7.45 (m, 5.36H), 7.26 (dd, J = 4.0, 2.3 Hz, 0.42H), 7.14 (dd, J
+
11
16
4
=
4.8, 3.9 Hz, 1H), 5.48 (t, J = 9.3 Hz, 0.42H), 5.19 (s, 0.42H), 4.10
found 243.0774.
(
=
d, J = 15.3 Hz, 2H), 2.95 (dd, J = 24.9, 11.6 Hz, 0.42H), 2.77 (dd, J
14.8, 6.8 Hz, 0.42H); C NMR (101 MHz, CDCl ): δ 184.5 (d, J =
3
13
Dimethyl (2-(2-chlorophenyl)-2-oxoethyl)phosphonate (4b)
5
1
.3 Hz), 144.0, 134.7, 134.6, 131.8, 131.8, 30.7 (d, J = 9.8 Hz),
28.2 (d, J = 12.3 Hz), 128.0, 126.0, 124.3, 122.8, 43.9 (d, J = 57.4
1
Colorless liquid; 60% yield (157.2 mg). H NMR (400 MHz,
CDCl ): δ 7.70-7.80 (m, 2H), 7.28-7.40 (m, 4H), 6.98-7.24 (m, 9H),
.54-4.70 (m, 1H), 2.90-3.05 (m, 1H), 1.05 (dd, J = 7.2, 16.8 Hz,
H); C NMR (100 MHz, CDCl ): δ 139.3 (d, J = 4.2 Hz), 135.5 (d,
J = 96.8 Hz), 132.2 (d, J = 8.3 Hz), 130.7 (d, J = 4.2 Hz), 130.6,
28.6 (d, J = 11.3 Hz), 128.1 (d, J = 11.0 Hz), 127.9, 127.5 (d, J =
1.2 Hz), 126.7, 53.6 (d, J = 3.0 Hz), 37.2 (d, J = 69.5 Hz), 16.8.
31
3
Hz); P NMR (162 MHz, CDCl ): δ 33,3, 26.7. HRMS (ESI-TOF)
m/z: (M+H) Calcd for C H O PS 329.0765, found 329.0676.
HRMS (ESI-TOF) m/z: (M+H) Calcd for C H O PS 327.0609,
found 327.0613.
3
4
3
+
18
18
+
2
13
3
18
16
2
1
1
(2-Hydroxy-2-(3-(trifluoromethyl)phenyl)ethyl)diphenylphosphine
+
HRMS (ESI-TOF) m/z: (M+H) Calcd for C H ClO P 263.0240,
oxide (3v)
10 13
4
found 263.0254.
o
1
White solid; m.p. 178-179 C, 10% yield (39.0 mg). H NMR
Supplementary data
(400 MHz, CDCl ): δ 8.03-8.13 (m, 2H), 7.55-7.65 (m, 4H), 7.45-
3
7
2
2
1
.50 (m, 1H), 7.36-7.42 (m, 1H), 7.15-7.25 (m, 3H), 7.05-7.13 (m,
H), 6.95-7.05 (m, 1H), 4.28-4.42 (m, 1H), 3.07-3.20 (m, 1H), 2.81-
Experimental procedures, characterization data, and copies of
the H NMR and C NMR spectra for the products are available.
1
13
13
.91 (m, 1H); C NMR (101 MHz, CDCl ): δ 135.4 (d, J = 5.7 Hz),
3
33.2, 132.4 (d, J = 2.7 Hz), 131.9 (d, J = 2.7 Hz), 131.2 (d, J = 2.8
Acknowledgements
Hz), 130.2 (d, J = 9.4 Hz), 129.2 (d, J = 11.4 Hz), 128.7 (d, J = 11.8
Authors express gratitude to the National Natural Science
Foundation of China (No. 21472133), the Priority Academic
Program Development of Jiangsu Higher Education Institutions
31
Hz), 127.0, 123.7, 39.4 (d, J = 64.6 Hz), 29.7 (d, J = 69.1 Hz).
P
+
NMR (162 MHz, CDCl ): δ 32.8. HRMS (ESI-TOF) m/z: (M+H)
3
Calcd for C H F O P 391.1075, found 391.1084.
21
19
3
2
(PAPD) and Key Laboratory of Organic Synthesis of Jiangsu
(2-Hydroxy-2-(4-nitrophenyl)ethyl)diphenylphosphine oxide (3w)
Province (KJS1749).
o
1
Yellow solid; m.p. 170-171 C, 25% yield (92.1 mg). H NMR
(
7
400 MHz, CDCl ): δ 8.16 (d, J = 8.8 Hz, 2H), 7.77-7.86 (m, 2H),
.66-7.74 (m, 2H), 7.44-7.65 (m, 8H), 5.53 (s, 1H), 5.28 (t, J = 10.1
3
References and notes
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3
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The reactions of styrenes bearing ortho-substituent gave the selective β-hydroxyphosphine oxide products via a radical
passway. A combination of steric and electronic factors played an important role in this reaction.

No interest statement for this manuscript need to be declared.