Nickel-catalyzed C–P cross-coupling of (het)aryl tosylates with secondary phosphine oxides

Article abstract of DOI:10.1177/1747519821994533

A novel and convenient approach to the synthesis of various tertiary phosphine oxides via nickel-catalyzed cross-coupling of (het)aromatic tosylates with secondary phosphine oxides is developed. The reaction employs cheap nickel as the catalyst, 1-(2-(di-tert-butylphosphanyl)phenyl)-4-methoxypiperidine (L3) as the ligand, and pyridine as the base. This reaction produces the corresponding (het)aromatic phosphorus compounds in good to high yields. Moreover, four new tertiary phosphine oxides are reported in this process.

Full text of DOI:10.1177/1747519821994533

994533CHL0010.1177/1747519821994533Journal of Chemical ResearchHe
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Research Paper
Journal of Chemical Research
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Nickel-catalyzed C–P cross-coupling of (het)aryl
tosylates with secondary phosphine oxides
https://doi.org/10.1177/1747519821994533
DOI: 10.1177/1747519821994533
journals.sagepub.com/home/chl
Xiao-Yun He
Abstract
A novel and convenient approach to the synthesis of various tertiary phosphine oxides via nickel-catalyzed cross-
coupling of (het)aromatic tosylates with secondary phosphine oxides is developed. The reaction employs cheap nickel
as the catalyst, 1-(2-(di-tert-butylphosphanyl)phenyl)-4-methoxypiperidine (L3) as the ligand, and pyridine as the base.
This reaction produces the corresponding (het)aromatic phosphorus compounds in good to high yields. Moreover, four
new tertiary phosphine oxides are reported in this process.
Keywords
C-P bond, (het)aromatic tosylates, nickel-catalyzed, phosphorylation, tertiary phosphine oxides
Date received: 23 December 2020; accepted: 25 January 2021
first examples of reactions of triarylbismuths with P(O)-H
Introduction
compounds under Pd(0) catalysis (Scheme 1, c).16
The development of efficient methods for preparing aryl phos-
Furthermore, microwave-(MW) and visible-light-irradi-
phorus compounds is of great importance because of their
ated P-C coupling reactions have also been developed
wide application in medicinal chemistry, materials chemistry,
(Scheme 1, d).17–19 To date, very few examples of nickel-
and organic synthesis,1,2 and their arylphosphine derivatives
catalyzed phosphinations of aryl mesylates and tosylates
play an important role in organometallic catalysis3,4 and
have been reported. In 2012, Zhang’s group reported the first
organocatalysis.5,6 Following on from the pioneering work of
Ni-catalyzed P-arylation using aryl mesylates and tosylates
the Hirao group in this area,7 after further development and
as coupling partners in this field, greatly expanding the scope
modification, researchers have developed the palladium-,
of transition-metal-catalyzed C-P couplings.20 Yu’s group
nickel-, and copper-catalyzed processes for the construction of
has reported a novel phosphorylation of alkenyl and aryl
C(sp)2-P bonds (Scheme 1, a).8–10 Recently, oxidative phos-
C–O bonds via photoredox/nickel dual catalysis.21 A variety
phonylation of arylboronic acids catalyzed by palladium or
of easily available and inexpensive sulfonates could be trans-
nickel has become feasible (Scheme 1, b).11,12 Diaryliodonium
formed into alkenyl phosphonates and aryl phosphine oxides
salts,13 as important and valuable electrophilic arylation rea-
gents, have attracted significant attention in recent years due to
their high reactivity and nontoxicity and they have been found
Department of Chemistry and Environmental Engineering, Hebei
to serve as potential arylating agents for phosphorus nucleo-
philes (Scheme 1, c). The last two decades have witnessed the
rapid development of bismuth chemistry. Organobismuth
compounds are nontoxic and are easily available building
blocks among the heavy nonradioactive main group
elements.14,15 Recently, Zhao and co-workers described the
Chemical and Pharmaceutical College, Shijiazhuang, P.R. China
Corresponding author:
Xiao-Yun He, Department of Chemistry and Environmental Engineering,
Hebei Chemical and Pharmaceutical College, Shijiazhuang 050026, P.R.
China.
Email: 61027391@qq.com
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2
Journal of Chemical Research
modest in our system, L1 was shown to be among the
most active ligands in their report. Encouraged by the
catalytic abilities of L1, and the needs of our current
research, we have designed several new ligands. Next, a
subsequent screening of the role of different ligands to
gain more insight and to find a more active and robust
system was undertaken (Table 1, entries 1 and 10–17).
Notably, in the course of these investigations, most of the
ligands examined gave fairly poor results, with only
bidentate ligand L3 that was giving excellent results in
promoting the reaction (Table 1, entry 11). The yield was
slightly improved by increasing the molar amount of
Ni(cod)2/L3 (Table 1, entry 18). Screening of different
bases showed that pyridine (Py) was the most suitable
base for this procedure, giving 3a in 75% yield (Table 1,
entries 18–25). Investigation of different solvents in this
transformation was carried out and the results indicated
that the solvent plays a crucial role in this reaction system.
THF/toluene (3:1) gave the best yield of 85% (Table 1,
entries 26–30). Increasing the amount of Py gave a slightly
better yield (Table 1, entry 31) and prolonging the reac-
tion time further increased the yield to 93% under other-
wise identical conditions (Table 1, entry 32).
Previous Work
O
[Pd] or [Cu] or [Ni]
ligand, base
X
P
Ph
Ph
+
HOPPh2
(a)
X=Br, I, OTf, OC(O)tBu, OC(O)i
PrO, OC(O)NMe
2, C(O)NHNH2
O
B(OH)2
P
Ph
[Pd] or [Ni]
ligand, base
Ph
+
HOPPh2
(b)
(c)
O
H
R2
[Pd]
P
O
O
R2
O
+
1/3 Ar3Bi
R1
P
R1
ligand, base
O
H
P
[Cu]
ligand, base
R2
O
R1
+
R
I X
P
R1
R2
2
O
X
blue LED or MW
hv or (254 nm)
P
R
R
(d)
+
HOPR2
X = Cl, Br, I
This Work
O
H
O
P
[Ni]
+
P
HetAr
Z2
HetAr
OTs
Z1
Z2
Z1
ligand, base
Scheme 1. Methods for the synthesis of tertiary phosphine
Thus, the optimized experimental conditions are as fol-
lows: Ni(cod)2/L3 (5.0 mol%), Py (2.0 equiv.) as the base in
THF/toluene (v/v: 3:1) at 50 °C. The scope of this method
was extended to the reaction of a wide range of (het)aryl
tosylates with different secondary phosphine oxides. As
shown in Table 2, different secondary phosphine oxides were
all efficiently coupled under these reaction conditions to pro-
vide the corresponding P-(het)arylated derivatives with good
to excellent isolated yields, showing that this protocol is a
general and practical method for the preparation of various
valuable symmetric or nonsymmetric tertiary phosphines
oxides. The scope of the substrates was mainly examined by
varying the N-heteroaromatic tosylate compounds, which
are key to many metal-catalyzed organic transformations.23,24
First, eight (het)aryl tosylates were coupled with Ph2P(O)H
2a to produce the corresponding products in good to high
yields. High yields were obtained with both electron-rich and
electron-deficient (het)aryl tosylates (Table 2, entries 1–7).
The reaction was inefficient under the current reaction condi-
tions from sesamol derivatives, reaction with 2a gave the
desired product 3i in only 35% yield (Table 2, entry 8). In
addition to diphenylphosphine oxide, when the aromatic
group was substituted with other groups, secondary phos-
phine oxides with electron-donating groups or electron-with-
drawinggroupsreactedsmoothlywithhydroxybenzothiazolyl
tosylates to provide the desired products in excellent yields
(Table 2, entries 11 and 12).
oxides.
with high selectivity and efficiency under mild reaction con-
ditions. Very recently, Li reported the nickel-catalyzed phos-
phorylation of aryl tosylates; however, the use of an
appropriate phosphine ligand was crucial for this reaction.22
Ten significant ligands were then evaluated for their efficacy
in this C–P bond coupling reaction, with the bidentate phos-
phine ligand 2-(di-tert-butylphosphino)-4-methoxyl-N,N-
dimethylaniline L1 proving to be the best candidate. On the
basis of Li’s developed system, we were interested in
Ni-catalyzed coupling of 2-pyridyl tosylate 1a with diphe-
nylphosphine oxide 2a as a model reaction system to opti-
mize the catalytic conditions (Table 1).
Results and discussion
Initially, when 1a (0.2 mmol) was added to a mixture of 2a (0.3
mmol),
Ni(cod)2/L1
(3.0
mol%),
and
N,N-
Diisopropylethylamine(DIPEA)(1.5equiv.)inTetrahydrofuran
(THF)/toluene (3:1) at 100 °C for 18 h under nitrogen, the
desired P-arylation product 3a was obtained in 48% yield
(Table 1, entry 1). Encouraged by this result, we further exam-
ined the effect of the catalyst, the solvent, the ligand, the tem-
perature, and the base on the reaction yield. Under similar
reaction conditions, various Ni salts were examined, with
Ni(cod)2 being the most effective catalyst for the production of
3a (Table 1, entries 1–4). In addition, the catalytic efficiency of
various nickel complexes was evaluated (Table 1, entries 5–9).
The results showed that among several nickel complexes,
NiCl2(dcype) was a potential catalyst, affording the desired
product 3a in 20% yield (Table 1, entry 8).
However, secondary phosphine oxides with strong elec-
tron-withdrawing groups, such as fluoro, resulted in a lower
yield. These results indicate that the yields were dependent
primarily on the electronic properties of the secondary
phosphine oxides (Table 2, entry 11). Secondary phosphine
oxides with sterically demanding o-substituted aromatic
rings afforded inferior yields, illustrating that steric hin-
drance has an influence on this coupling reaction (Table 2,
entry 9).
We, in Li’s report, have described recently the applica-
tion of L1 as a catalyst ligand for the cross-coupling of
aryltosylate and dialkyl phosphite, despite the reactivity is

He
3
Table 1. Optimization of the reaction conditions.a
H
P
O
N
N
/
ligand, base
[Ni]
+
OTs
P O
solvent, Temp, time
2a
1a
3a
Entry [Ni]/ligandb
Base
Solvent
Yieldc
Entry [Ni]/ligand
Base
Solvent
Yield (%)c
1d
Ni(cod)2/L1
DIPEA Toluene 48
17d
18
19
20
21
22
23
24
25e,f
26
27e
28b
29g
30
31h
32i
Ni(cod)2/L9 DIPEA
Ni(cod)2/L3 DIPEA
Ni(cod)2/L3 TMEDA Toluene
Ni(cod)2/L3 t-BuOLi Toluene
Ni(cod)2/L3 t-BuOK Toluene
Ni(cod)2/L3 K2CO3
Ni(cod)2/L3 K3PO4
Ni(cod)2/L3 Py
Toluene
Toluene
38
69
45
11
9
18
15
75
n.r.
53
n.r.
78
80
2d
Ni(OAc)2•4H2O/L1 DIPEA Toluene Trace
Ni(acac)2/L1
NiCl2/L1
3d
DIPEA Toluene 43
DIPEA Toluene n.r.
DIPEA Toluene n.r.
DIPEA Toluene Trace
DIPEA Toluene n.r.
DIPEA Toluene 20
4d,e
5d,e
6d
NiCl2(PCy3)2
NiCl2(dppe)
NiCl2(PPh3)2
NiCl2(dcype)
NiCl2(dppf)
Ni(cod)2/L2
Ni(cod)2/L3
Ni(cod)2/L4
Ni(cod)2/L5
Ni(cod)2/L6
Ni(cod)2/L7
Ni(cod)2/L8
Toluene
Toluene
Toluene
Toluene
Dioxane
Acetonitrile
THF
7d,e
8d
9d
DIPEA Toluene
8
Ni(cod)2/L3
–
10d
11d
12d
13d
14d
15d
16d
DIPEA Toluene 51
DIPEA Toluene 62
DIPEA Toluene 45
Ni(cod)2/L3 Py
Ni(cod)2/L3 Py
Ni(cod)2/L3 Py
Ni(cod)2/L3 Py
Ni(cod)2/L3 Py
Ni(cod)2/L3 Py
Ni(cod)2/L3 Py
DIPEA Toluene
5
THF
DIPEA Toluene 31
DIPEA Toluene 12
DIPEA Toluene 40
THF/toluene (v/v: 3:1) 85
THF/toluene (v/v: 3:1) 89
THF/toluene (v/v: 3:1) 93
O
O
N
N
N
P
N
N
N
P
N
N
P
N
O
P
P
P
O
P
P
P
L9
L6
L8
L3
L2
L4
L5
L7
L1
aUnless otherwise stated, the reaction conditions are as follows: Heteroaromatic tosylate (1a) (0.2 mmol), diphenyl phosphite (2a) (0.3 mmol),
[Ni]/ligand (5.0 mol%), base (1.5 equiv.), solvent (2 mL), reaction time was 12 h, N2.
bStirred at 80 °C.
cYield of isolated product.
d[Ni]/ligand (3.0%).
eNo reaction.
fNo base was used.
gStirred at 50 °C.
hPy (2.0 equiv.).
iPy (2.0 equiv.), reaction time was 18 h.
We also tested our cross-coupling procedure for the (het)aryl phenol derivatives are used to form the C-P bond.
assembly of a bis(heterocyclic) product. A 2-hydroxyben- These advantages should help this C-P bond-forming
zothiazolyl tosylate readily underwent coupling with dith- method to find broad application in both complex molecule
iophenylphosphine oxide to provide a bis(heterocyclic) synthesis and for the preparation of P-chiral organophos-
compound (Table 2, entry 13). Other hydrogen phosphoryl phorus compounds.
compounds were also applicable in this transformation. In
addition to diarylphosphine oxides 2a–f, aliphatic
n-Bu2P(O)H (Table 2, entry 14), the Cy2P(O)H (Table 2,
entries 15–17), and bulky t-Bu2P(O)H (Table 2, entries
18–22) coupled with (het)aryl tosylates readily by increas-
Experimental
General
ing the equivalent of base, producing the corresponding
products in moderate to high yields.
Ni(cod)2 (98%), Ni(acac)2 (>98%), NiCl2(PCy3)2 (>98%),
NiCl2(dppe) (98%), NiCl2(dcype) (>98%), NiCl2(dppf)
(99%), NiCl2(PPh3)2 (>98%), Pd2dba3, Pd(OAc)2, and
DiPPF were purchased from Aldrich. Ni(OAc)2·4H2O,
NiCl2, racemic-2,2’-Bis(diphenylphosphino)-1,1’-binaph-
thyl (BINAP), and Tetramethylethylenediamine (TMEDA)
(⩾99%) were purchased from Alfa Aesar. Other reagents
were available commercially and were used without further
purification, unless otherwise indicated. All aryl tosylates
were prepared according to the literature procedures.25–29
Ligands L1, L2, L6, L7, L8, and L9 were prepared
Conclusion
In summary, we have developed a novel nickel-catalyzed
carbon-phosphine cross-coupling protocol from a wide
range of (het)aromatic tosylates and different secondary
phosphine oxides. Notably, the process is simple and pro-
ceeds under mild reaction conditions. Moreover, the pro-
cess is generally cheaper overall because more accessible

4
Journal of Chemical Research
Table 2. Cross-coupling of various heteroaromatic tosylates with disubstituted phosphine oxide.a
L3
Ni(cod)2/
Py (2.0 equiv)
5.0mol%
H
P
Z1
N
O
Z2
HetAr
O
+
P
THF/toluene, 50oC,18-24h
HetAr
OTs
Z1
P
Z2
O
3
1
2
Entry
Substrate 1 Substrate 2 Product
Yieldb (%)
Entry
Substrate 1 Substrate 2 Product
Yieldb (%)
CF3
CF3
S
O
P
N
O
N
O
P
H
O
P
P
N
H
CF3
CF3
OTs
1
2
3
4
1b
2a
3b
83
92
83
86
12
13
14
15
1j
1j
1j
1j
2e
3m
87
72
73
78
S
S
O
P
S
S
O
P
O
P
N
H
S
S
S
OTs
1c
2a
2a
2a
3c
2f
3n
S
O
P
O
P
O
P
N
N
H
N
OTs
1d
3d
2g
3oc
N
S
O
P
O
O
P
N
N
H
P
OTs
1e
3e
O
2h
3pc
O
O
P
O
P
O
P
H
O
OTs
5
6
7
1f
2a
2a
2a
3f
85
88
89
16
17
18
1f
2h
3qc
75
71
70
S
O
P
O
P
O
P
S
N
H
OTs
1g
3g
1a
1a
2h
3rc
N
O
P
N
O
S
O
P
N
P
H
S
OTs
1h
3h
O
2i
3sc
O
N
O
O
P
O
P
O
OTs
8
9
1i
2a
3i
35
77
19
20
1b
1c
2i
2i
3tc
75
74
S
S
O
P
O
P
O
P
N
H
S
N
OTs
1j
1j
1j
2b
3j
3uc
S
O
P
O
P
N
H
O
P
N
10
11
2c
3k
3l
88
56
21
22
1d
1e
2i
2i
3vc
76
73
F
F
S
O
P
N
O
P
N
H
O
P
F
F
2d
3wc
aReaction conditions: heteroaromatic tosylate (1a) (0.2 mmol), diphenyl phosphite (2) (0.3 mmol), Ni(cod)2/L2 (5.0 mol%), Py (2.0 equiv.), THF/
toluene (v/v: 3/1) (2 mL), N2, at 50 °C for 18–24 h.
bYield of the isolated product.
cPy (3.5 equiv.).

He
5
silica, which in turn was washed with CH2Cl2. Removal of
the solvent from the combined eluent afforded the Ligand
L4 in 63% yield that was further purified by recrystalliza-
tion or by washing with appropriate solvents. All ligands
were worked up in air and were found to be stable when
handled on the bench top. Ligand L3 was prepared by the
coupling of (tbutyl)2PH and 1-(2-bromophenyl)-4-meth-
oxypiperidine, via the standard procedure employing 3
mol% Pd and 3.6 mol% ligand DiPPF in 57% yield as a
white solid (Scheme 2).
NH
7
Br
N
P
HPtBu2
Br
O
4
L5
N
H
5
O
O
O
HPtBu2
N
N
HPCy2
N
P
Br
P
6
L4
L3
1-(2-(di-tert-butylphosphanyl)phenyl)-4-methoxypiperi-
1
dine (L3): H NMR (400 MHz, CDCl3): δ 7.63–7.55 (m,
Scheme 2. Synthesis of ligands L3, L4, and L5.
1H), 7.30–7.21 (m, 1H), 7.10–7.04 (m, 2H), 3.34 (s, 3H),
3.32–3.26 (m, 1H), 3.24–3.18 (m, 2H), 2.88–2.79 (m, 2H),
2.05–1.97 (m, 2H), 1.94–1.83 (m, 2H), 1.24 (d, J = 14.8
according to literature procedures.22,30–33 Reactions were
run under an argon atmosphere with exclusion of moisture
from reagents and glassware using standard Schlenk tech-
niques. Solvents were dried from molecular sieves and kept
under argon. Spectroscopic data of known compounds
matched with the data reported in the corresponding refer-
ences.34–42 All new compounds were further characterized
by high-resolution mass spectrometry (HRMS) (EI), ele-
Hz, 18H). 13C NMR (100 MHz, CDCl3): δ 159.2 (d, JPC
=
17.2 Hz), 136.5, 133.7 (d, JPC = 18.6 Hz), 130.6, 123.4,
121.2, 75.2, 55.3, 44.7, 44.6, 33.8 (d, J = 24 Hz), 30.8 (d, J
= 14.8 Hz). 31P NMR (162 MHz, CDCl3): δ −26.4.
(HRMS) (EI): m/z [M]+ calcd for C20H34NOP: 335.2378;
found: 335.2373. Anal. calcd for C20H34NOP: C, 71.61; H,
10.22; N, 4.18; found: C, 71.73; H, 10.29; N, 4.31.
1-(2-Dicyclohexylphosphinophenyl)-4-methoxypiperidine
(L4): Colorless oil, yield 63%. 1H NMR (400 MHz, CDCl3):
δ 7.60–7.53 (m, 1H), 7.30–7.20 (m, 1H), 7.11–7.03 (m,
2H),3.35 (s, 3H), 3.32–3.26 (m, 1H), 3.24–3.21 (m, 2H),
2.86–2.81 (m, 2H), 2.01–1.94 (m, 8H), 1.77–1.63 (m, 8H),
1.33–0.95 (m, 10H). 13C NMR (100 MHz, CDCl3): δ 161.3
(d, JPC = 17.2 Hz), 133.2, 132.0 (d, JPC = 18.0 Hz), 129.3,
123.6, 120.9, 75.0, 55.2, 44.7, 44.6, 35.3 (J = 13.0 Hz), 31.2
(J = 20.4 Hz), 29.8 (J = 8.8 Hz), 27.4, 27.2 (J = 4.8 Hz),
26.5. 31P NMR (162 MHz, CDCl3): δ −23.5.
1
mental analysis, and 31P, H, and 13C NMR spectroscopy.
High-resolution mass spectra were obtained using a GCT
time of flight (TOF) instrument with the electron ionization
(EI) source. Elemental analyses were performed with the
German elemental analyzer Vario EL. NMR measured on
Bruker 400M spectrometers. 1H NMR and 13C NMR were
recorded using tetramethylsilane (TMS) as the internal
standard and 85% H3PO4 as the external standard for 31P
NMR spectra. Chemical shifts are reported in parts per mil-
lion (δ). The peak patterns are indicated as follows: s, sin-
glet; d, doublet; t, triplet; dd, doublet of doublets; dt,
doublet of triplets; and m, multiplet. The coupling con-
stants, J, are reported in Hertz (Hz). The products were
purified by column chromatography on aladdin silica gel
(300–400 mesh) under an argon atmosphere.
(HRMS) (EI): m/z [M]+ calcd for C24H38NOP: 387.2691;
found: 387.2687. Anal. calcd for C24H38NOP: C, 74.38; H,
9.88; N, 3.61; found: C, 74.43; H, 9.93; N, 3.72.
1-(2-(di-tert-butylphosphanyl)phenyl)piperidine (L5):
1
Colorless oil, yield 53%. H NMR (400 MHz, CDCl3): δ
7.61–7.54 (m, 1H), 7.32–7.23 (m, 1H), 7.12–7.00 (m, 2H),
2.75–2.73 (m, 4H), 1.37–1.32 (m, 6H), 1.25 (d, J = 14.2
Hz, 18H). 13C NMR (100 MHz, CDCl3): δ 158.9 (d, JPC
=
Experimental section
17.0 Hz), 136.3, 133.6 (d, JPC = 18.2 Hz), 130.4, 123.1,
121.0, 54.3, 33.7 (d, J = 23.6 Hz), 30.8 (d, J = 15.0 Hz),
26.6, 24.3. 31P NMR (162 MHz, CDCl3): δ −22.3.
General procedure A: ligand synthesis and characterization. A
Schlenk tube was charged with reagents: Pd2dba3 (46 mg, 5
mol% Pd), BINAP (93 mg, 7.5 mol%), NaOtBu (231 mg,
2.4 mmol, 1.2 equiv.), 1,2-dibromobenzene (4) (2.0 mmol),
and 4-methoxypiperidine (5) (2.0 mmol, 1.0 equiv.). Tolu-
ene (5 mL) and a stir bar were added. Then, the mixture was
then stirred in an oil bath at 80 °C for 15 h under Ar. Upon
completion, the mixture was concentrated and the residue
was purified by column chromatography on silica gel (elu-
ent: hexanes/ethyl acetate) to afford the desired product (6)
in 71% yield.
(HRMS) (EI): m/z [M]+ calcd for C19H32NP: 305.2272;
found: 305.2276. Anal. calcd for C19H32NP: C, 74.71; H,
10.56; N, 4.59; found: C, 74.75; H, 10.59; N, 4.62.
General procedure B: phosphination of
(Het)aromatic tosylates with secondary
phosphine oxides
To a Schlenk tube, Pd(OAc)2 (typically 3 mol%) and
DiPPF [1,1′-bis(diisopropylphosphino)ferrocene; Pd:L =
1:1.2], di(cyclohexyl)phosphine (1.2 mmol), and NaOtBu
(1.44 mmol) were added, followed by the aryl halide 6 (1.2
mmol) in toluene (6 mL). The Schlenk tube was then
degassed twice. The resulting mixture was heated at 110 °C
until complete consumption of the phosphine was achieved.
The solution was then cooled and filtered through a plug of
In an argon-filled glovebox, an oven-dried Schlenk tube
equipped with a Teflon stir bar was charged with
Ni(cod)2/L3 (5 mol%) followed by anhydrous THF (1.0
mL), secondary phosphine oxide (2) (0.3 mmol), and Py
(2.0 equiv.). The solution was stirred for 5–10 min. Next,
the (het)aromatic tosylate (1) (0.2 mmol) was added at once
followed by anhydrous toluene/THF (0.5 mL/0.5 mL). The
Schlenk tube was sealed with a Teflon valve and

6
Journal of Chemical Research
the reaction mixture was stirred at 50 °C for 18–24 h. The Acknowledgements
reaction mixture was then cooled to room temperature, fil-
The author is thankful to Hebei University of Science and
1
Technology for 13C NMR, H NMR, 31P NMR, HRMS(EI), and
tered, and rinsed with dichloromethane to remove any
insoluble residues. The filtrate was concentrated in vacuo
and the residue was purified by flash column chromatogra-
phy on silica gel to give the analytically pure product. All
products prepared using this synthetic method (3a, 3b, 3c,
3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3l, 3m, 3n, 3o, 3p, 3q, 3r, 3s)
have been reported earlier, and their spectral data matched
with those presented in the literature. Products 3t, 3u, 3v,
and 3w are novel compounds.
elemental analysis.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
di-tert-butyl(pyridin-3-yl)phosphine oxide (3t): Colorless
oil, yield 75%. 1H NMR (400 MHz, CDCl3): δ 8.65–8.61 (m,
2H, H pyridine), 8.02–7.98 (m, 1H, H pyridine), 7.41–7.37
(m, 1H, H pyridine), 1.23 (d, J = 13.0 Hz, 18H). 13C NMR
(100 MHz, CDCl3): δ 152.2, 152.0 (d, J = 12.2 Hz), 139.2 (d,
J = 7.8 Hz), 132.0, 131.2 (d, J = 106.2 Hz), 35.7 (d, J = 75.1
Hz), 34.9 (d, J = 74.9 Hz), 27.0, 26.2. 31P NMR (162 MHz,
CDCl3): δ48.7. (HRMS) (EI): m/z [M]+ calcd for C13H22NOP:
239.1439; found: 239.1436. Anal. calcd for C13H22NOP: C,
65.25; H, 9.27; N, 5.85; found: C, 65.35; H, 9.31; N, 5.90.
di-tert-butyl(thiophen-2-yl)phosphine oxide (3u):
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: The
author gratefully acknowledges the financial support from Hebei
Chemical and Pharmaceutical College and the Higher Education
Scientific Research Project of Hebei Province (2020) (SQ201044).
ORCID iD
Xiao-Yun He
https://orcid.org/0000-0002-4540-9788
Supplemental material
Supplemental material for this article is available online.
1
Colorless oil; yield 74%. H NMR (400 MHz, CDCl3): δ
7.70–7.65 (m, 1H, H thiophene), 7.51–7.46 (m, 1H, H
thiophene), 7.22–7.17 ( m, 1H, H thiophene), 1.22 (d, J =
13.2 Hz, 18H). 13C NMR (100 MHz, CDCl3): δ 135.7 (d,
J = 8.1 Hz), 132.6 (d, J = 4.2 Hz), 132.8 (d, J = 102.1
Hz), 128.8 (d, J = 12.0 Hz), 35.8 (d, J = 75.6 Hz), 35.1
(d, J = 75.3 Hz), 27.2, 26.5. 31P NMR (162 MHz, CDCl3):
δ 46.6.
References
1. Yoshino K, Kohno T, Tsukamoto G, et al. J Med Chem 1989;
32: 1528.
2. Hérault D, Nuel D, Buono G, et al. Chem Soc Rev 2015; 44:
2508.
3. McCarthy M and Guiry PJ. Tetrahedron 2001; 57: 3809.
4. Surry DS and Buchwald SL. Chem Sci 2011; 2: 27.
5. Lu X, Zhang C and Xu Z. Acc Chem Res 2001; 34: 535.
6. Wei Y and Shi M. Acc Chem Res 2010; 43: 1005.
7. Hirao T, Masunaga T, Ohshiro Y, et al. Bull Chem Soc Jpn
1982; 55: 909.
8. Rao HH, Jin Y, Zhao YF, et al. Chem Eur J 2006; 12: 3636.
9. Huang J, Liu Z, Zhang B, et al. Inorg Chem 2019; 58: 4253.
10. Dong JY, Liu L, Han LB, et al. Org Lett 2019; 21: 3198.
11. Fu TT, Qiao HW, Zhao YF, et al. Org Biomol Chem 2014;
18: 2895.
12. Hu GB, Chen WZ, Zhao YF, et al. Org Lett 2013; 15: 5362.
13. Xu J, Zhang PB, Zhao YF, et al. J Org Chem 2013; 78: 8176.
14. Suzuki H and Matano Y. Organo-bismuth chemistry.
Amsterdam: Elsevier, 2001.
15. Maeda S and Patai S. In the chemistry of organic arsenic,
antimony and bismuth compounds. New York: Wiley, 1994,
p. 725.
16. Wang T, Sang S, Zhao YF, et al. J Org Chem 2014; 79: 608.
17. Zeng HY, Dou Q and Li CJ. Org Lett 2019; 21: 1301.
18. Ananthnag GS, Mague JT and Balakrishna MS. Dalton
Trans 2015; 44: 3785.
19. Zhu DL, Jiang S, Li HX, et al. Org Lett 2021; 23: 160.
20. Shen CR, Yang GQ and Zhang WB. Org Biomol Chem 2012;
10: 3500.
21. Liao LL, Gui YY and Yu DG. Org Lett 2017; 19: 3735.
22. Li CJ. Russ Gen Chem 2020; 90: 725.
23. Minnaard AJ, Feringa BL, Vries JG, et al. Acc Chem Res
2007; 40: 1267.
(HRMS) (EI): m/z [M]+ calcd for C12H21OPS: 244.1051;
found: 244.1046. Anal. calcd for C12H21OPS: C, 58.99; H,
8.66; S, 13.12; found: C, 59.01; H, 8.71; S, 13.16.
di-tert-butyl(quinolin-8-yl)phosphine oxide (3v): Yellow
1
oil; yield 76%. H NMR (400 MHz, CDCl3): δ 8.82–8.75
(m, 1H, H quinoline), 8.39 (dd, 1H, J = 14.0, J = 7.2 Hz,
H quinoline), 8.23 (d, 1H, J = 8.1 Hz, H quinoline), 8.08
(d, 1H, J = 7.2, H quinoline), 7.73–7.68 (m, 1H, H quino-
line), 7.46–7.41 (m, 1H, H quinoline), 1.24 (d, J = 12.8 Hz,
18H). 13C NMR (100 MHz, CDCl3): δ 151.2, 149.5 (d, J =
4.4 Hz), 138.1 (d, J = 7.2 Hz), 136.3, 133.9 (d, J = 109.4
Hz), 133.5, 132.3, 128.7 (d, J = 11.2 Hz), 121.8, 36.3 (d, J
= 77.1 Hz), 35.8 (d, J = 76.9 Hz), 27.8, 26.9. 31P NMR
(162 MHz, CDCl3): δ 36.9.
(HRMS) (EI): m/z [M]+ calcd for C17H24NOP: 289.1596;
found: 289.1593. Anal. calcd for C17H24NOP: C, 70.57; H,
8.36; N, 4.84; found: C, 70.63; H, 8.41; N, 4.89.
di-tert-butyl(quinolin-6-yl)phosphine
oxide
(3w):
Yellow oil; yield 73%. 1H NMR (400 MHz, CDCl3): δ 9.05
(s, 1H), 8.40–8.37 ( m, 1H, H quinoline), 8.25–8.22 ( m,
1H, H quinoline), 8.20–8.17 (m, 1H, H quinoline), 7.88–
7.84 ( m,1H, H quinoline), 7.55–7.51 (m, 1H, H quinoline),
1.23 (d, J = 12.6 Hz, 18H). 13C NMR (100 MHz, CDCl3):
δ 152.3, 149.3, 137.1, 134.3 (d, J = 9.2 Hz), 132.3, 132.2
(d, J = 105.6 Hz), 130.8 (d, J = 11.0 Hz), 129.9 (d, J =
11.2 Hz), 122.4, 36.1 (d, J = 76.2 Hz), 35.4 (d, J = 75.6
Hz), 27.4, 26.7. 31P NMR (162 MHz, CDCl3): δ 37.8.
(HRMS) (EI): m/z [M]+ calcd for C17H24NOP: 289.1596;
found: 289.1591. Anal. calcd for C17H24NOP: C, 70.57; H,
8.36; N, 4.84; found: C, 70.64; H, 8.43; N, 4.88.
24. Diederich F and Stang PJ. Metal-catalyzed cross-coupling
reactions. Weinheim: Wiley-VCH Verlag GmbH, 1998.
25. Yang JF, Zheng JF, Zhou JR, et al. Eur J Med Chem 2012;
31: 6248.
26. Lei XY, Stafford JM, Cao B, et al. Synthesis 2015; 47: 2578.

He
7
27. Kwong FY, Lee HW, So CM, et al. Org Chem Front 2020; 35. Zhang HY, Sun M, Yang SD, et al. Org Biomol Chem 2012;
7: 926. 10: 9627.
28. Langille NF, Dakin LA, Panek JS, et al. Org Lett 2002; 4: 36. Yang J, Chen TQ and Han LB. J Am Chem Soc 2015; 137:
2485.
1782.
29. Belley M, Douida Z, Mancuso J, et al. Synlett 2005; 2: 247.
37. Isshiki R, Muto K and Yamaguchi J. Org Lett 2018; 20: 1150.
30. Cheng K, Zeng MF, Qi CZ, et al. J Med Chem 2013; 37: 99. 38. Luo K, Chen YZ, Wu L, et al. Org Lett 2016; 18: 452.
31. Harada T, Ueda Y, Sawamura M, et al. Chem Commun 2018; 39. Li L, Wang JJ, Wang GW, et al. J Org Chem 2016; 81: 5433.
54: 1718.
40. Peng P, Peng L, Lei AW, et al. Org Chem Front 2016; 6:
749.
32. Bedford RB, Brenner PB, Carter E, et al. Organometallics
2014; 33: 5767.
41. Stankevič M and Wɫodarczyk A. Tetrahedron 2013; 69: 73.
33. Li PB, Fu CL, Ma SM, et al. Adv Synth Catal 2013; 35: 1255. 42. Gowrisankar S, Neumann H, Beller M, et al. Chem Eur J
34. Yun J, To WP, Che CM, et al. Org Lett 2018; 20: 7816.
2013; 19: 15979.