Polystyrene-cross-linking Ortho-substituted triphenylphosphines: Synthesis, coordination properties, and application to Pd-catalyzed cross-coupling of aryl chlorides

Article abstract of DOI:10.1246/bcsj.20170141

Polystyrene-cross-linking triphenylphosphines having methyl groups as ortho substituents were synthesized. Coordination of the polymer-bound tri(o-tolyl)phosphine-type ligand toward a Pd(II) complex was investigated by ³¹PCP/MASNMR spectroscopi

Full text of DOI:10.1246/bcsj.20170141

Advance Publication Cover Page
Polystyrene-Cross-Linking Ortho-Substituted Triphenylphosphines: Synthesis,
Coordination Properties, and Application to Pd-Catalyzed Cross-Coupling of
Aryl Chlorides
Tomohiro Iwai,* Kiichi Asano, Tomoya Harada, and Masaya Sawamura*
Advance Publication on the web May 19, 2017
doi:10.1246/bcsj.20170141
© 2017 The Chemical Society of Japan

Polystyrene-Cross-Linking Ortho-Substituted Triphenylphosphines: Synthesis,
Coordination Properties, and Application to Pd-Catalyzed Cross-Coupling of Aryl
Chlorides
Tomohiro Iwai,* Kiichi Asano, Tomoya Harada, and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
E-mail: iwai-t@sci.hokudai.ac.jp, sawamura@sci.hokudai.ac.jp
Tomohiro Iwai is an Assistant Professor of Hokkaido University. He received his Bachelor (2006) and Master (2008) of
Science degrees from Hokkaido University. He received his Ph.D. degree from Kyoto University in 2011 under the
supervision of Professor Yasushi Tsuji. Since 2011, he has been an Assistant Professor at Hokkaido University.
Masaya Sawamura is a Professor of Hokkaido University. He received his Ph.D. degree from Kyoto University in 1989
under the supervision of Professor Yoshihiko Ito. In 1989, he joined the faculty of the same department as Assistant
Professor. He spent one year as a researcher at Harvard University (Professor Stuart L. Schreiber, 1993–1994). In 1995,
he moved to Tokyo Institute of Technology and to the University of Tokyo to join the group of Professor Eiichi
Nakamura as an Assistant Professor. He was promoted to Lecturer in 1996 and to Associate Professor in 1997. Since
2001, he has been a Full Professor at Hokkaido University. He received The Chemical Society of Japan Award for
Young Scientists (1996), The Chemical Society of Japan Award for Creative Work (2012) and Nagoya Silver Medal of
Organic Chemistry (2017).
Abstract
Polystyrene-cross-linking triphenylphosphines having
the ortho-methyl substituent were evaluated in the Pd-catalyzed
cross-coupling of aryl chlorides.
methyl groups as ortho substituents were synthesized.
Coordination of the polymer-bound tri(o-tolyl)phosphine-type
ligand toward a Pd(II) complex was investigated by 31P
Previous Work
P
This Work
CP/MAS
NMR
spectroscopies.
Effects
of
the
R3
R2
(PS)
(PS)
ortho-methyl-substituent were evaluated in the Pd-catalyzed
cross-coupling of aryl chlorides.
P
R1
(PS)
(PS)
tBu
(PS)
tBu
(PS)
(PS)
(PS)
(PS)
(PS)
(PS)
(PS)
tBu
tBu
1. Introduction
tBu
tBu
Tertiary phosphines are widely used as ligands for
transition metal catalysts.1 Thus, their structural modification is
important for the control of catalytic activity. The introduction
of ortho-substituents to aromatic rings of triarylphosphines has
a strong impact on the catalytic activity through steric effects.2
Tolman’s cone angle is a common parameter to quantify the
steric bulk of phosphines.3 For example, tri(o-tolyl)phosphine
had a much larger cone angle (194°) than the parent ligand
triphenylphosphine (145°).
We previously designed and synthesized a new type of
polystyrene-cross-linking triphenylphosphine PS-TPP (Figure 1,
left).4 Owing to spatial isolation of the P center in the polymer
matrix by the threefold cross-linking,5-7 PS-TPP formed
mono-P-ligated metal complexes selectively. Such metal
complexes exhibited high catalytic performances in the
Pd-catalyzed cross-coupling of unactivated aryl chlorides, for
which importance of mono-P-ligation of bulky phosphines is
well-established.8 Thus, we next paid our attention to effects of
steric demand around the P center in PS-TPP on catalytic
performances.
Polystyrene-Cross-Linking
PS-TPP
Ortho-Substituted TPPs
Figure 1. Polystyrene-cross-linking TPPs.
2. Results and Discussion
Preparation of polystyrene-cross-linking ortho-
substituted triphenylphosphines. We adopted a methyl group
as an ortho substituent because utility of tri(o-tolyl)phosphine
is well-established.9 Initially, we began to prepare threefold
vinylated triphenylphosphine derivatives as threefold
cross-linkers for the polymer-bound phosphines (Scheme 1).
For
the
preparation
of
C3-symmetric
tri(o-tolyl)phosphine-type cross-linker CL2, we followed our
previous procedure developed for the synthesis of CL1 with a
slight modification (aryllithium reagents instead of
arylmagnesium reagents) (Scheme 1, top).4 Specifically, PCl3
was reacted with aryllithium reagents prepared in situ from the
corresponding aryl bromides (1 and 2) and nBuLi.
Non-C3-symmetric tertiary phosphines CL3 and CL4
were synthesized in a stepwise manner (Scheme 1, center
and bottom). The synthesis of CL3 started from the reaction
This article reports the synthesis and characterization of
polystyrene-cross-linking
substituted
triphenylphosphine
derivatives having one or more ortho-tolyl groups instead of
the P-phenyl groups of the parent PS-TPP phosphine ligand
(Figure 1, right). Coordination of the polymer-bound
tri(o-tolyl)phosphine-type ligand toward a Pd(II) complex was
investigated by 31P CP/MAS NMR spectroscopy. The effects of
of
dichloro(diethylamino)phosphine
with
the
ortho-methyl-substituted aryllithium reagent followed by
chlorination with dry HCl, to give diarylchlorophosphine A. A
subsequent reaction of A with p-styryllithium afforded CL3 in

an acceptable yield. CL4 containing the single
ortho-methyl-substituted aryl group were obtained via
aryldichlorophosphines B, which was prepared from
bis(diethylamino)chlorophosphine as a P source.
Table 1. Swelling Propertiya)
Swelling Ratio in Organic Solvents
Polymers
Toluene
2.1
THF
2.0
Hexane
1.6
DMF
1.1
PS-TPP
PS-oMe-TPP
PS-oMe2-TPP
PS-oMe3-TPP
2.3
2.2
1.8
1.0
2.5
2.4
1.8
1.1
R
R
1) nBuLi (3.1–3.3 equiv)
THF, –78 °C
2.6
2.1
1.6
1.0
Br
P
3
2) PCl3 (1 equiv)
THF, –78 °C to rt
a) Original volume in drying was 2.0–2.1 mL/g.
(3.2–3.3 equiv)
1 (R = H)
2 (R = Me)
CL1 (R = H) 63%
CL2 (R = Me) 54%
Table 2. 31P CP/MAS NMR and 31P NMR Chemical Shifts
Li
1) nBuLi (2.1 equiv)
THF, –78 °C
d1
Cross-
Linkers
d2
Dd
Me
Polymers
(ppm)a)
(ppm)b)
(d1–d2)
P
2) PCl2(NEt2) (1.0 equiv)
THF, –78 °C to rt
(1.1 equiv)
2
Ar2PCl
2
PS-TPP
–6
–15
–23
–31
CL1
CL4
CL3
CL2
−6.3
–13.9
–21.5
–29.4
0
–1
–2
–2
THF
–78 °C to rt
3) HCl (2.0 equiv)
THF, 0 °C to rt
(2.15 equiv)
A
PS-oMe-TPP
PS-oMe2-TPP
PS-oMe3-TPP
CL3 24%
Ar = 2-Me-4-CHCH2-C6H3
Li
1) nBuLi (1.1 equiv)
THF, –78 °C
Me
a) 31P CP/MAS NMR. b) 31P NMR in CDCl3.
P
2) PCl(NEt2)2 (1.0 equiv)
THF, –78 °C to rt
(2.1 equiv)
2
ArPCl2
2
THF
–78 °C to rt
3) HCl (4.0 equiv)
THF, 0 °C to rt
(1.2 equiv)
B
CL4 22%
–31
Me
Me
(PS)
Ar = 2-Me-4-CHCH2-C6H3
P
(PS)
Me
tBu
(PS)
Scheme 1. Synthesis of CL1–4.
(PS)
(PS)
tBu
(PS)
PS-oMe3-TPP
tBu
As shown in Scheme 2, three types of
polystyrene-cross-linking ortho-substituted
triphenylphosphines (PS-oMe-TPP, PS-oMe2-TPP and
36
27 (unidentified)
Ar3P=O
PS-oMe3-TPP) were prepared through radical emulsion
polymerization between 4-t-butylstyrene as a monomer and
CL2–4 as threefold cross-linkers (monomer/cross-linker 60:1)
according to the reported protocol for the synthesis of PS-TPP
(Divinylbenzene co-cross-linker was not used).4,10 The ortho
substituents in the phosphine cross-linkers did not significantly
affect co-polymerization efficacies (81 vs. 75–77 wt% yields).
These polystyrene-monophosphine hybrids were obtained as
bead-shaped insoluble colorless materials. These cross-linked
polymers showed good swellabilities toward common organic
solvents as PS-TPP (Table 1). Indeed, swelling was good with
toluene and THF, moderate with hexane, but poor with DMF.
The 31P CP/MAS NMR analysis showed relatively broad
signals due to inhomogeneity of the cross-linked polymers (half
δ / ppm
–10
110
90
70
50
30
10
–30
–50
–70
–90
–110
Figure 2. 31P CP/MAS NMR spectrum of PS-oMe3-TPP.
Coordination toward
a
Pd(II) species. As
a
representative of the prepared polystyrene-cross-linking
ortho-substituted triphenylphosphines, PS-oMe3-TPP was
examined for coordination properties toward a Pd metal
through the reaction with PdCl2(PhCN)2 in CH2Cl2 at rt. The
reaction caused coloring of the beads in orange-brown. The
beads were filtered, washed and dried in vacuo. The 31P
CP/MAS NMR spectra of the resulting materials suggested
selective formation of mono-P-ligated Pd species
PdCl2(L)(PS-oMe3-TPP) (L = PhCN or solvent), irrespective of
the P loading relative to Pd (P/Pd 1:2, 1:1, 2:1; Figure 3). When
P was excess (P/Pd 2:1; Figure 3c), the free phosphine
line width for PS-oMe3-TPP: ca. 20 ppm, Figure 2).11 Their 31
P
NMR chemical shifts were comparable to those of the
corresponding cross-linkers (CL2–4) as was the case for their
parent phosphine PS-TPP (Table 2, Dδ = 0 to –2), suggesting
no significant change of steric and electronic features of the P
centers after the polymerization.12
remained.
In
contrast,
the
soluble
counterpart
tri(o-tolyl)phosphine was completely consumed with the same
P loading relative to Pd (P/Pd 1:1 or 2:1; Figure 4), giving a
bis-P-ligated Pd species.13 Thus, the polymer-cross-linking was
crucial for selective mono-P ligation.
R3
R2
(PS)
R3
tBu
R2
R1
(PS)
P
P
R1
(60 equiv)
tBu
(PS)
(PS)
AIBN (1.2 equiv)
acacia gum, NaCl
PhCl/H2O (1:20)
80 °C, 24 h
(PS)
tBu
(PS)
[P] ~0.10 mmol/g
CL1–4
tBu
From CL1; PS-TPP (R1 = R2 = R3 = H)
81%
From CL4; PS-oMe-TPP (R1 = Me, R2 = R3 = H) 75%
From CL3; PS-oMe2-TPP (R1 = R2 = Me, R3 = H) 77%
From CL2; PS-oMe3-TPP (R1 = R2 = R3 = Me)
77%
Scheme 2. Synthesis of polystyrene-cross-linking TPPs.

PdCl2(PhCN)2 as a catalyst precursor (1 mol% Pd). The results
are summarized in Table 3.
25
(a)
PdCl2(L)
Me
Me
(PS)
As described in our previous report,4 the parent ligand
PS-TPP successfully catalyzed the coupling reaction to give the
desired product 5 in 98% yield (Table 3, entry 1). PS-oMe-TPP
induced catalytic activity, but the reaction efficacy was slightly
decreased (93%, entry 2). Even lower reaction efficacies were
observed with more hindered ligands, PS-oMe2-TPP and
PS-oMe3-TPP (entries 3 and 4). However, it should be noted
that the use of the corresponding soluble ligands
P
(PS)
Me
tBu
(PS)
(PS)
(PS)
tBu
(PS)
tBu
PdCl2(L)(PS-oMe3-TPP)
*
spinning
side bands
* *
δ / ppm
–90 –110
[triphenylphosphine,
diphenyl(o-tolyl)phosphine,
–10
110
90
70
50
30
10
–30
–50
–70
phenyldi(o-tolyl)phosphine and tri(o-tolyl)phosphine] resulted
in almost no reaction under otherwise the same conditions
(<2% yields, entries 5–8), indicating the importance of the
polystyrene-cross-linking. The advantage of the polymer-bound
triphenylphosphines over their soluble counterparts were also
observed in the Pd-catalyzed Buchwald–Hartwig amination of
1-butyl-4-chlorobenzene (3b) with aniline (6) in the present of
NaOtBu as a base (Table 4).
The observed negative effects of the ortho substituents in
the polymer-cross-linking systems toward catalytic efficacy
seem to be contradictory to those in the homogeneous systems.
However, this can be reasonable if oxidative addition of Ar–Cl
to Pd(0) is catalyst-turnover-limiting irrespective of the ligand
used. That is, increase in the steric demand of the phosphine
seems to be beneficial in the homogeneous systems because it
causes increase in the distribution of active mono-P-ligated Pd
species while the ease of mono-P-ligation does not depend on
the ortho substituents in the polymer-cross-linking system. The
substituent effect in the latter may be rather unfavorable for
some reasons: Enhanced catalyst deactivation or decrease in the
reactivity toward transmetalation may be considered.
(b)
25
PdCl2(L)
Me
Me
(PS)
P
(PS)
Me
tBu
(PS)
(PS)
(PS)
PS-oMe3-TPP
tBu
(PS)
tBu
PdCl2(L)(PS-oMe3-TPP)
–30
*
spinning
side bands
*
*
δ / ppm
–90 –110
–10
110
90
70
50
30
10
–30
–50
–70
–32
(c)
PdCl2(L)
Me
Me
(PS)
PS-oMe3-TPP
P
(PS)
25
Me
tBu
(PS)
(PS)
(PS)
tBu
(PS)
tBu
PdCl2(L)(PS-oMe3-TPP)
spinning
side bands
*
*
δ / ppm
–90 –110
–10
110
90
70
50
30
10
–30
–50
–70
Figure 3. 31P CP/MAS NMR spectra obtained from
PS-oMe3-TPP and PdCl2(PhCN)2 [P/Pd (a) 1:2, (b) 1:1 and (c)
2:1; L = PhCN or solvent].
Table 3. Ligand Effects in the Pd-catalyzed Suzuki–
Miyaura Reaction of 3a with 4a)
PdCl2(PhCN)2 (1 mol%)
Ligand (2 mol%)
+
Me
Cl
(HO)2BPh
Me
Ph
KF (3 equiv)
THF (1 mL), 25 °C, 18 h
3a (0.25 mmol)
4 (1.5 equiv)
5
27.4
(a)
PdCl2(L){(o-tol)3P}
Entry
Ligand
PS-TPP
Yield (%)b
1
2
3
4
5
6
7
8
98 (95)
PS-oMe-TPP
PS-oMe2-TPP
PS-oMe3-TPP
Ph3P
Ph2(o-tol)P
Ph(o-tol)2P
(o-tol)3P
93
85
67
0
0
0
27.3
(b)
22.9
PdCl2(L){(o-tol)3P}
PdCl2{(o-tol)3P}2
δ / ppm
–10
110
90
70
50
30
10
–30
–50
–70
–90
–110
2
Figure 4. 31P NMR spectra (CDCl3) obtained from (o-tol)3P
and PdCl2(PhCN)2 [P/Pd (a) 1:1 and (b) 2:1; L = PhCN or
solvent]
a) Conditions: 3a (0.25 mmol), 4 (0.375 mmol), PdCl2(PhCN)2
(1 mol%), ligand (2 mol%), KF (0.75 mmol), THF (1 mL),
25 °C, 18 h. b) Yields were determined by H NMR analysis.
1
An isolated yield is shown in parentheses.
Palladium-Catalyzed
Cross-Coupling
of
Aryl
Chlorides. To evaluate effects of ortho-methyl substituents of
polystyrene-cross-linking triphenylphosphines toward catalytic
activities, we examined the room-temperature Pd-catalyzed
Suzuki–Miyaura cross-coupling of an unactivated aryl chloride,
for which the utility of PS-TPP have previously been
demonstrated.4,14
Specifically,
the
reaction
between
4-chlorotoluene (3a, 0.25 mmol) and phenylboronic acid (4, 1.5
equiv) was conducted in THF at 25 °C with KF as a base and

Table 4. Ligand Effects in the Pd-catalyzed Buchwald–
Hartwig Amination of 3b with 6a)
(Alumina
Activated
200,
Nakarai
Tesque,
Inc.).
4-Bromostyrene (1) was purchased from TCI Co.
1-Bromo-2-methyl-4-vinylbenzene (2) was synthesized
according to the literature with slight modifications.15
Phenylboronic acid (4) was recrystallized from hot water
before use.
[PdCl(π-allyl)]2 (Pd: 1 mol%)
Ligand (2 mol%)
+
Bu
Cl
H2NPh
Bu
NH
Ph
NaOtBu (1.4 equiv)
toluene (1 mL), 100 °C, 20 h
3b (0.25 mmol)
6 (1.2 equiv)
7
Preparation of CL1 (Scheme 1). In
a 100-mL
round-bottom flask equipped with a magnetic stirring bar,
nBuLi (1.64 M in hexane, 4.02 mL, 6.6 mmol, 3.3 equiv) was
slowly added to the solution of 4-bromostyrene (1, 1.21 g, 6.6
mmol, 3.3 equiv) in THF (30 mL) at –78 °C. After the mixture
was stirred for 1 h at –78 °C, PCl3 (0.275 g, 2.0 mmol) was
added at this temperature over 5 min. The mixture was warmed
to rt and stirred for 4 h. After quenching with aq. NH4Cl, the
mixture was extracted with CHCl3. The organic layer was
washed with water, dried over MgSO4, filtered, and
concentrated. The residue was purified by silica gel column
chromatography (hexane/EtOAc 100:0 to 95:5) to give CL1 as
white solids (0.429 g, 63% yield). 1H NMR (400 MHz,
CDCl3): δ 5.27 (d, J = 11.2 Hz, 3H), 5.77 (d, J = 17.6 Hz, 3H),
6.69 (dd, J = 17.6, 11.2 Hz, 3H), 7.24–7.30 (m, 6H), 7.30–7.39
(m, 6H). 13C NMR (100.5 MHz, CDCl3): δ 114.69 (3C),
126.28 (d, JC–P = 7.6 Hz, 6C), 133.84 (d, JC–P = 20.2 Hz, 6C),
136.31 (3C), 136.56 (d, JC–P = 10.6 Hz, 3C), 137.93 (3C). 31P
NMR (161.8 MHz, CDCl3): δ –6.3. The title compound has
been prepared previously.4
Entry
Ligand
Yield (%)b
1
2
3
4
5
6
7
8
PS-TPP
90 (90)
PS-oMe-TPP
PS-oMe2-TPP
PS-oMe3-TPP
Ph3P
Ph2(o-tol)P
Ph(o-tol)2P
(o-tol)3P
23
38
10
4
3
10
4
a) Conditions: 3b (0.25 mmol), 6 (0.30 mmol), [PdCl(p-allyl)]2
(Pd: 1 mol%), ligand (2 mol%), NaOtBu (0.35 mmol), toluene
(1 mL), 100 °C, 20 h. b) Yields were determined by H NMR
1
analysis. An isolated yield is shown in parentheses.
3. Conclusion
We
synthesized
polystyrene-cross-linking
triphenylphosphines having ortho-methyl-substituents through
radical emulsion polymerization of 4-t-butylstyrene with the
corresponding tris(p-styryl)phosphine derivatives as threefold
Preparation of CL2 (Scheme 1). In
round-bottom flask equipped with a magnetic stirring bar,
nBuLi (1.64 M in hexane, 1.89 mL, 3.1 mmol, 3.1 equiv) was
a 100-mL
cross-linkers.
Coordination
behavior
of
the
slowly
added
to
the
solution
of
tri(o-tolyl)phosphine-type ligand PS-oMe3-TPP toward
PdCl2(PhCN)2 was investigated by 31P CP/MAS NMR
spectroscopy. The NMR study suggested a mono-P-ligating
feature of PS-oMe3-TPP as in the case of the parent ligand
PS-TPP. The polystyrene-cross-linking ortho-substituted TPP
1-bromo-2-methyl-4-vinylbenzene (2, 0.630 g, 3.2 mmol, 3.2
equiv) in THF (10 mL) at –78 °C. After the mixture was stirred
for 1 h at –78 °C, PCl3 (0.137 g, 1.0 mmol) was added at this
temperature over 5 min. The mixture was warmed to rt and
stirred for 12 h. After quenching with aq. NH4Cl, the mixture
was extracted with CHCl3. The organic layer was washed with
water, dried over MgSO4, filtered, and concentrated. The
residue was purified by silica gel column chromatography
(hexane/EtOAc 100:0 to 95:5) to give CL2 as white solids
(0.208 g, 54% yield). M.p. ~108.8 °C (decomp.). 1H NMR
(400 MHz, CDCl3): δ 2.38 (s, 9H), 5.26 (d, J = 11.2 Hz, 3H),
5.77 (d, J = 16.8 Hz, 3H), 6.65–6.72 (m, 6H), 7.12 (dd, J = 7.6,
1.2 Hz, 3H), 7.26–7.28 (m, 3H). 13C NMR (100.5 MHz,
CDCl3): δ 21.18 (d, JC–P = 21.1 Hz, 3C), 114.24 (3C), 123.98
(3C), 127.90 (d, JC–P = 4.7 Hz, 3C), 133.27 (3C), 134.03 (d, JC–
ligands
induced
the
Pd-catalyzed
Suzuki–Miyaura
cross-coupling and Buchwald–Hartwig amination of aryl
chlorides with ligand performances lower than those of the
parent PS-TPP ligand.
4. Experimental
Generals. Solution NMR spectra were recorded on a
JEOL ECX-II (400 MHz for 1H NMR, 100.5 MHz for 13C
NMR, and 161.8 MHz for 31P NMR). Chemical shift values are
referenced to Me4Si (1H; 0 ppm), CDCl3 (13C; 77.0 ppm), and
H3PO4 (31P; 0 ppm). Magic angle spinning (MAS) NMR
spectra were recorded on a Bruker MSL-300 spectrometer,
operating at 75.5 MHz for 13C NMR, and 121.5 MHz for 31P
NMR. High-resolution mass spectra (Thermo Scientific
Exactive for ESI-MS) were recorded at the Instrumental
Analysis Division, Global Facility Center, Creative Research
Institution, Hokkaido University. IR spectra were measured a
PerkinElmer Frontier instrument. Melting points were
determined on a micro melting point apparatus using micro
cover glass (Yanaco MP-500D). TLC analyses were performed
on commercial glass plates bearing 0.25-mm layer of Merck
Silica gel 60F254. Silica gel (Kanto Chemical Co., Ltd., Silica
gel 60 N, spherical, neutral) was used for column
chromatography.
= 10.6 Hz, 3C), 136.50 (3C), 137.83 (3C), 142.77 (d, JC–P
=
P
26.8 Hz, 3C). 31P NMR (161.8 MHz, CDCl3): δ –29.4. IR
(ATR): 3007, 2914, 1627, 1596, 1546, 1477, 1446, 1379, 987,
908, 830, 740, 693 cm–1. ESI-HRMS (m/z): [M+H]+ cacld for
C27H28P, 383.19231; found, 383.19220.
Preparation
Chlorobis(2-methyl-4-vinylphenyl)phosphine A was prepared
by following procedure: In 20-mL Schlenk flask,
dichloro(diethylamino)phosphine (0.435 g, 2.50 mmol, 1.0
equiv) was added to solution of
of
CL3
(Scheme
1).
a
a
a
(2-methyl-4-vinylphenyl)lithium, which was prepared from 2
(1.06 g, 5.38 mmol, 2.15 equiv) and nBuLi (1.6 M in hexane,
3.28 mL, 5.25 mmol, 2.1 equiv) in THF (10 mL) at –78 °C, and
the mixture was stirred for 1 h at –78 °C. After being warmed
to rt, the mixture was again cooled to 0 °C. After addition of
HCl (4 M in 1,4-dioxane, 1.25 mL, 5.0 mmol, 2.0 equiv) at
0 °C, the mixture was stirred for 1 h at 0 °C, and then warm to
rt. After removal of volatiles under vacuum, the residue was
suspended with Et2O.
All reactions were carried out under nitrogen or argon
atmosphere. Materials were obtained from commercial
suppliers or prepared according to standard procedures unless
otherwise noted. 4-t-Butylstyrene (>90% GC purity, stabilized
with 4-t-butylcatechol) was purchased from TCI Co., Ltd., and
were purified by passing through an alumina column before use
The solution of A in Et2O was slowly transferred to
another 100-mL round-bottom flask with (p-styryl)lithium,

which was prepared from 1 (0.527 g, 2.90 mmol, 1.15 equiv)
and nBuLi (1.53 M in hexane, 1.80 mL, 2.75 mmol, 1.1 equiv)
in THF (10 mL) at –78 °C for 1 h, via cannula capped with a
filter paper at –78 °C. The mixture was warmed to rt and stirred
for 12 h. After quenching with MeOH, the mixture was
concentrated. The residue was purified by silica gel column
chromatography (hexane/EtOAc 100:0 to 97:3) to give CL3 as
rapidly stirred aqueous solution. The mixture was stirred at
80 °C for 24 h. After being cooled to rt, the mixture was filtered
through a glass adaptor equipped with a cotton plug, washed
successively with H2O, MeOH, toluene, THF and MeOH, and
dried in vacuo at 100 °C to give the polymer PS-TPP as white
beads (4.03 g, 81 wt%). Obtained beads were passed through a
series of sieves, and the beads with 250–710 µm size in
diameter were used for catalytic reactions. The P loading was
calculated to be 0.10 mmol/g on the basis of ratio of the used
monomers, and was used in the catalytic application for
convenience. 31P CP/MAS NMR (121.5 MHz): δ –6. 13C
CP/MAS NMR (75.5 MHz): δ 32, 34, 37–55 (m), 117–137 (m),
143, 148.
1
white amorphous solids (0.222 g, 24% yield). H NMR (400
MHz, CDCl3): δ 2.38 (s, 6H), 5.24–5.30 (m, 3H), 5.74–5.81 (m,
3H), 6.64–6.76 (m, 5H), 7.13 (d, J = 7.6 Hz, 2H), 7.21 (t, J =
8.0 Hz, 2H), 7.26–7.27 (m, 2H), 7.38 (d, J = 8.0 Hz, 2H). 13C
NMR (100.5 MHz, CDCl3): δ 21.18 (d, JC–P = 21.2 Hz, 2C),
114.30 (2C), 114.64, 123.89 (2C), 126.43 (d, JC–P = 6.6 Hz, 2C),
127.91 (d, JC–P = 4.8 Hz, 2C), 133.11 (2C), 134.43 (d, JC–P
20.2 Hz, 2C), 134.77 (d, JC–P = 10.6 Hz, 2C), 134.98 (d, JC–P
=
=
Preparation of PS-oMe-TPP. The radical emulsion
polymerization between 4-t-butylstyrene (2.75 mL, 2.41 g,
>90% purity, 15 mmol) and CL4 (0.0886 g, 0.25 mmol) gave
PS-oMe-TPP as white beads (1.88 g, 75 wt%, 0.10 mmol/g).
31P CP/MAS NMR (121.5 MHz): δ –15. 13C CP/MAS NMR
(75.5 MHz): δ 32, 34, 37–55 (m), 117–137 (m), 143, 148.
Preparation of PS-oMe2-TPP. The radical emulsion
polymerization between 4-t-butylstyrene (2.75 mL, 2.41 g,
>90% purity, 15 mmol) and CL3 (0.0921 g, 0.25 mmol) gave
PS-oMe2-TPP as white beads (1.92 g, 77 wt%, 0.10 mmol/g).
31P CP/MAS NMR (121.5 MHz): δ –23. 13C CP/MAS NMR
(75.5 MHz): δ 32, 34, 37–55 (m), 117–137 (m), 143, 148.
Preparation of PS-oMe3-TPP. The radical emulsion
polymerization between 4-t-butylstyrene (2.75 mL, 2.41 g,
>90% purity, 15 mmol) and CL2 (0.0956 g, 0.25 mmol) gave
PS-oMe3-TPP as white beads (1.93 g, 77 wt%, 0.10 mmol/g).
31P CP/MAS NMR (121.5 MHz): δ –31. 13C CP/MAS NMR
(75.5 MHz): δ 32, 34, 37–55 (m), 117–137 (m), 143, 148.
9.5 Hz), 136.41, 136.47 (2C), 137.87 (2C), 137.99, 142.50 (d,
JC–P = 25.9 Hz, 2C). 31P NMR (161.8 MHz, CDCl3): δ –21.5.
IR (ATR): 3086, 2984, 1627, 1595, 1547, 1475, 1380, 1286,
992, 915, 907, 833, 740 cm–1. ESI-HRMS (m/z): [M+H]+ cacld
for C26H26P, 369.17666; found, 369.17670.
Preparation
Dichloro(2-methyl-4-vinylphenyl)phosphine B was prepared
by following procedure: In 20-mL Schlenk flask,
bis(diethylamino)chlorophosphine (0.526 g, 2.50 mmol, 1.0
equiv) was added to solution of
of
CL4
(Scheme
1).
a
a
a
(2-methyl-4-vinylphenyl)lithium, which was prepared from 2
(0.591 g, 3.00 mmol, 1.2 equiv) and nBuLi (1.54 M in hexane,
1.78 mL, 2.75 mmol, 1.1 equiv) in THF (10 mL) at –78 °C, and
the mixture was stirred for 1 h at –78 °C. After being warmed
to rt, the mixture was cooled to 0 °C. After addition of HCl (4
M in 1,4-dioxane, 2.50 mL, 5.25 mmol, 4.0 equiv) at 0 °C, the
mixture was stirred for 1 h at 0 °C, and then warm to rt. After
removal of volatiles under vacuum, the residue was suspended
with Et2O.
Swelling Test (Table 1).
polystyrene-cross-linking triphenylphosphines (diameter: 250–
710 µm) was performed according to the literature.16
A
swelling test of
A
The solution of B in Et2O was slowly transferred to
another 100-mL round-bottom flask with (p-styryl)lithium,
which was prepared from 1 (1.01 g, 5.50 mmol, 2.2 equiv) and
nBuLi (1.54 M in hexane, 3.41 mL, 5.25 mmol, 2.1 equiv) in
THF (10 mL) at –78 °C for 1 h, via cannula capped with a filter
paper at –78 °C. The mixture was warmed to rt and stirred for
15 h. After quenching with MeOH, the mixture was
concentrated. The residue was purified by silica gel column
chromatography (hexane/CH2Cl2 95:5 to 85:15) to give CL4 as
graduated 0.5-mL syringe equipped with a filter paper at the
exit was charged with ca. 50 mg of the PS resin, and an
appropriate solvent (0.5 mL) was added to the vessel. After the
mixture was let stand for 5–10 min for equilibration, the extra
solvent was removed from the syringe by using the plunger.
The volume of the swollen resin was recorded.
Reactions of PS-oMe3-TPP and PdCl2(PhCN)2 (Figure
3). PS-oMe3-TPP (200 mg, 0.02 mmol) and PdCl2(PhCN)2
(0.04 mmol for P/Pd 1:2; 0.02 mmol for P/Pd 1:1; 0.01 mmol
for P/Pd 2:1) were placed in a 5-mL glass tube containing a
magnetic stirring bar. CH2Cl2 (2 mL) was added and stirred at
rt for 2 h. The mixture was filtered, washed and dried in vacuo
at rt. The mixture was analyzed with 31P CP/MAS NMR
spectroscopy.
Reactions of (o-tol)3P and PdCl2(PhCN)2 (Figure 4).
(o-tol)3P (18.3 mg, 0.06 mmol) and PdCl2(PhCN)2 (0.06 mmol
for P/Pd 1:1; 0.03 mmol for P/Pd 2:1) were placed in a 5-mL
vial containing a magnetic stirring bar. CDCl3 (2 mL) was
added and stirred at rt for 5 min. The mixture was analyzed
with 31P NMR spectroscopy.
A Typical Procedure for the Pd-catalyzed Suzuki–
Miyaura Reactions (Table 3, entry 1). In a nitrogen-filled
glove box, PS-TPP (50 mg, 0.005 mmol, 2 mol%), THF (0.5
mL) and a solution of PdCl2(PhCN)2 (0.96 mg, 0.0025 mmol, 1
mol% Pd) in THF (0.5 mL) were placed in a 10-mL glass tube
containing a magnetic stirring bar. After stirring at rt for 5 min.,
4-chlorotoluene (3a, 31.6 mg, 0.25 mmol, 1.0 equiv),
phenylboronic acid (4, 45.7 mg, 0.375 mmol, 1.5 equiv) and
KF (43.6 mg, 0.75 mmol, 3.0 equiv) were added. The tube was
sealed with a screw cap, and was removed from the glove box.
The mixture was stirred at 25 °C for 18 h. The mixture was
filtered through a Celite pad (eluting with Et2O). The volatiles
1
white amorphous solids (0.192 g, 22% yield). H NMR (400
MHz, CDCl3): δ 2.39 (s, 3H), 5.24–5.30 (m, 3H), 5.73–5.80 (m,
3H), 6.63–6.77 (m, 4H), 7.13 (d, J = 7.6 Hz, 1H), 7.19–7.26 (m,
5H), 7.37 (d, J = 8.0 Hz, 4H). 13C NMR (100.5 MHz, CDCl3):
δ 21.20 (d, JC–P = 21.1 Hz), 114.36, 114.66 (2C), 123.81,
126.36 (d, JC–P = 7.7 Hz, 4C), 127.90 (d, JC–P = 4.7 Hz), 132.98,
134.11 (d, JC–P = 20.1 Hz, 4C), 135.49 (d, JC–P = 11.5 Hz),
135.72 (d, JC–P = 9.2 Hz, 2C), 136.35 (2C), 136.40, 137.87,
137.96 (2C), 142.29 (d, JC–P = 24.9 Hz). 31P NMR (161.8 MHz,
CDCl3): δ –13.9. IR (ATR): 3086, 3063, 3006, 2984, 1627,
1595, 1547, 1494, 1392, 1091, 1015, 908, 831, 755 cm–1.
ESI-HRMS (m/z): [M+H]+ cacld for C25H24P, 355.16101;
found, 355.16110.
A
Typical
Procedure
for
Synthesis
of
Polystyrene-Cross-Linking Triphenylphosphines (Scheme
2). For PS-TPP: A solution of acacia gum (4.80 g) and NaCl
(6.00 g) in water (120 mL) was placed in a 500-mL
round-bottom flask equipped with a magnetic stirring bar, and
was deoxygenated by purging with Ar. Meanwhile, a solution
of 4-t-butylstyrene (5.5 mL, 4.81 g, >90% purity, 30 mmol),
CL1 (0.170 g, 0.50 mmol, 1.0 equiv) and AIBN (0.0985 g, 0.60
mmol, 1.2 equiv) in chlorobenzene (6 mL) was degassed by
three freeze-pump-thaw cycles, and was injected into the

were removed under reduced pressure, and an internal standard
(1,3,5-trimethoxybenzene) was added to determine the yield of
4-metyl-1,1’-biphenyl (5, 98% yield). The crude product was
purified by silica gel column chromatography (hexane) to give
Eggenhuisen, D. Nand, M. Baldus, B. M. Weckhuysen,
R. J. M. Klein Gebbink, P. C. A. Bruijnincx, Catal. Sci.
Technol. 2013, 3, 2571–2579. d) Q. Sun, M. Jiang, Z.
Shen, Y. Jin, S. Pan, L. Wang, X. Meng, W. Chen, Y.
Ding, J. Li, F.-S. Xiao, Chem. Commun. 2014, 50,
11844–11847. e) Y.-B. Zhou, C.-Y. Li, M. Lin, Y.-J. Ding,
Z.-P. Zhan, Adv. Synth. Catal. 2015, 357, 2503–2508. f)
T. Chen, F. Mao, Z. Qi, Y. Li, R. Chen, Y. Wang, J.
Huang, RSC Adv. 2016, 6, 16899–16903.
1
5 as white solids (39.8 mg, 0.237 mmol, 95% yield). H NMR
(400 MHz, CDCl3): δ 2.39 (s, 3H), 7.24 (d, J = 8.0 Hz, 2H),
7.31 (tt, J = 7.6, 1.2 Hz, 1H), 7.42 (t, J = 7.2 Hz, 2H), 7.49 (d, J
= 8.0 Hz, 2H), 7.57 (dd, J = 8.4, 1.2 Hz, 2H). 13C NMR (100.5
MHz, CDCl3): δ 21.09, 126.95 (2C + 2C +1C), 128.69 (2C),
129.46 (2C), 136.99, 138.32, 141.12.
6.
A related our work on tripod immobilization of
A Typical Procedure for the Pd-catalyzed Buchwald–
Hartwig Amination Reactions (Table 4, entry 1). In a
nitrogen-filled glove box, PS-TPP (50 mg, 0.005 mmol, 2
mol%), and a solution of [PdCl(p-allyl)]2 (0.46 mg, 0.00125
mmol, 1 mol% Pd) in toluene (1 mL) were placed in a 10-mL
glass tube containing a magnetic stirring bar. After stirring at rt
for 5 min., 1-butyl-4-chlorobenzene (3b, 42.2 mg, 0.25 mmol,
1.0 equiv), aniline (6, 27.9 mg, 0.30 mmol, 1.2 equiv) and
NaOtBu (33.6 mg, 0.35 mmol, 1.4 equiv) were added. The tube
was sealed with a screw cap, and was removed from the glove
box. The mixture was stirred at 100 °C for 20 h. The mixture
was filtered through a Celite pad (eluting with Et2O). The
volatiles were removed under reduced pressure, and an internal
standard (1,2-diphenylethane) was added to determine the yield
of 4-butyl-N-phenylaniline (7, 90% yield). The crude product
was purified by silica gel column chromatography
(hexane/EtOAc 100:0 to 99:1) to give 7 as yellow oil (50.8 mg,
triphenylphosphine on a silica gel surface: T. Iwai, R.
Tanaka, T. Harada, M. Sawamura, Chem. Eur. J. 2014,
20, 1057–1065.
7.
8.
A related our work on a polystyrene-cross-linking
bisphosphine: T. Iwai, T. Harada, H. Shimada, K. Asano,
M. Sawamura, ACS Catalysis 2017, 7, 1681–1692.
Selected reviews; a) R. Martin, S. L. Buchwald, Acc.
Chem. Res. 2008, 41, 1461–1473. b) G. C. Fu, Acc.
Chem. Res. 2008, 41, 1555–1564. c) C. A. Fleckenstein,
H. Plenio, Chem. Soc. Rev. 2010, 39, 694–711. d) R. J.
Lundgren, K. D. Hesp, M. Stradiotto, Synlett 2011, 2011,
2443–2458. e) S. M. Wong, C. M. So, F. Y. Kwong,
Synlett 2012, 2012, 1132–1153. f) P. G. Gildner, T. J.
Colacot, Organometallics 2015, 34, 5497–5508.
Selected examples a) R. F. Heck, Acc. Chem. Res. 1979,
12, 146–151. b) W. A. Herrmann, C. Brossmer, K. Öfele,
C.-P. Reisinger, T. Priermeier, M. Beller, H. Fischer,
Angew. Chem. Int. Ed. Engl. 1995, 34, 1844–1848. c) A.
Tillack, D. Hollmann, D. Michalik, M. Beller,
Tetrahedron Lett. 2006, 47, 8881–8885.
9.
1
0.225 mmol, 90% yield). H NMR (400 MHz, CDCl3): δ 0.93
(t, J = 7.2 Hz, 3H), 1.37 (sext, J = 7.2 Hz, 2H), 1.54–1.60 (m,
2H), 2.56 (t, J = 7.6 Hz, 2H), 5.61 (br-s, 1H), 6.88 (t, J = 7.6
Hz, 1H), 7.00–7.03 (m, 4H), 7.09 (d, J = 8.4 Hz, 2H), 7.22–
7.27 (m, 2H). 13C NMR (100.5 MHz, CDCl3): δ 13.98, 22.33,
33.82, 34.91, 116.87 (2C), 118.63 (2C), 120.25, 129.17 (2C),
129.25 (2C), 135.99, 140.40, 143.80.
10. The P loadings to polystyrene resins were calculated to
be ~0.10 mmol/g on the basis of ratio of the used
monomers. These calculated values were used in metal
coordination studies and catalytic applications.
11. In some cases, small amounts of phosphine oxides were
detected due to partial oxidation of the P atom during the
polymerization. See the Supporting Information for their
31P CP/MAS NMR spectra.
12. The slight upfield shift (Dδ ca. –2 ppm) is reasonable
owing to the electron-donating effects of the p-alkyl
substituents on the P-phenyl groups.
This work was supported by JSPS KAKENHI Grant
Numbers JP25810056 in Young Scientists (B) and JP16K13988
in Challenging Exploratory Research to T.I. and by JST ACT-C
Grant Number JPMJCR12YN, JST CREST, and JSPS
KAKENHI Grant Number JP15H05801 in Precisely Designed
Catalysts with Customized Scaffolding to M.S. T.H. thanks the
JSPS fellowship for young scientists.
13. T. Bartik, T. Himmler, J. Organometal. Chem. 1985, 293,
343–351.
Supporting Information
14. For selected examples of Pd-catalyzed Suzuki–Miyaura
Experimental procedures, spectral and analytical data.
cross-coupling
of
aryl
chlorides
with
This
material
is
available
on
http://
triphenylphosphine-based ligands, see: a) H. Ohta, M.
Tokunaga, Y. Obora, T. Iwai, T. Iwasawa, T. Fujihara, Y.
Tsuji, Org. Lett. 2007, 9, 89–92. b) T. Fujihara, S.
Yoshida, H. Ohta, Y. Tsuji, Angew. Chem., Int. Ed. 2008,
47, 8310–8314. c) D. J. M. Snelders, G. van Koten, R. J.
M. K. Gebbink, J. Am. Chem. Soc. 2009, 131, 11407–
11416. See also refs 4, 5a, 5e, 5f and 6.
dx.doi.org/10.1246/############.
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Graphical Abstract
<Title>
Polystyrene-Cross-Linking Ortho-Substituted Triphenylphosphines: Synthesis, Coordination Properties, and Application to
Pd-Catalyzed Cross-Coupling of Aryl Chlorides
<Authors' names>
Tomohiro Iwai,* Kiichi Asano, Tomoya Harada, and Masaya Sawamura*
<Summary>
Polystyrene-cross-linking triphenylphosphines having methyl groups as ortho substituents were synthesized. Coordination of
the polymer-bound tri(o-tolyl)phosphine-type ligand toward a Pd(II) complex was investigated by 31P CP/MAS NMR spectroscopies.
Effects of the ortho-methyl-substituent were evaluated in the Pd-catalyzed cross-coupling of aryl chlorides.
<Diagram>