Silica-supported tripod triarylphosphines: Application to palladium-catalyzed borylation of chloroarenes

Article abstract of DOI:10.1246/cl.131161

Silica-supported tripod triarylphosphines that have a Ph3Ptype core tripodally immobilized on a silica surface enabled the Pd-catalyzed borylation of chloroarenes with bis(pinacolato)diboron under mild conditions. The immobilization in tripod was crucial for the excellent performance of the Ph3P-based ligands.

Full text of DOI:10.1246/cl.131161

CL-131161
Received: December 11, 2013 | Accepted: December 29, 2013 | Web Released: January 9, 2014
Silica-supported Tripod Triarylphosphines:
Application to Palladium-catalyzed Borylation of Chloroarenes
Tomohiro Iwai, Tomoya Harada, Ryotaro Tanaka, and Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Hokkaido 060-0810
(E-mail: sawamura@sci.hokudai.ac.jp)
[PdCl(η3-cinnamyl)]2
(Pd: 0.5 mol %)
Silica-supported tripod triarylphosphines that have a Ph3P-
type core tripodally immobilized on a silica surface enabled the
Pd-catalyzed borylation of chloroarenes with bis(pinacolato)di-
boron under mild conditions. The immobilization in tripod was
crucial for the excellent performance of the Ph3P-based ligands.
O
O
O
O
Ligand (Pd/P 1:2)
+
Me
Cl
B B
Me
Bpin
KOAc (1.5 mmol)
benzene
25 °C, 10 h
1a (0.5 mmol)
2 (0.55 mmol)
3a
Ligand, 1H NMR yield of 3a
Me
P
Me
Me
Si
P
P
Me
Arylboronic acids and their derivatives are versatile inter-
mediates in organic synthesis because of their applicability
and broad functional group compatibility in many reactions,
less toxicity, and air- and moisture stability.1 The Pd-catalyzed
borylation of aryl halides with boron reagents (Miyaura
borylation) offers a method for synthesizing arylboronates with
excellent functional group compatibility.2-8 Recently, we re-
ported that a heterogeneous Pd catalyst system based on a silica-
supported monodentate trialkylphosphine ligand Silica-SMAP
shows an excellent performance for this catalytic reaction
allowing the use of a broad range of chloroarenes as substrates.9
We proposed that this catalytic performance of the Pd-
Silica-SMAP system originated from the novel characteristic of
the Silica-SMAP monodentate phosphine to favor monoligation
to the Pd atom and that this is due to the immobilization of the
phosphine molecule with restricted mobility and with a high
degree of directionality.10 In addition, we introduced other
immobilized phosphine ligands Silica-TRIP,10 Silica-3p-TPP,11
and PS-Ph3P,12 which are based on a common design concept
but have a triarylphosphine core in contrast to the Silica-SMAP
trialkylphosphine, and demonstrated these immobilized triaryl-
phosphines to be useful for the Pd-catalyzed Suzuki-Miyaura
coupling,11-13 the Buchwald-Hartwig amination,12 or Ir (Rh)-
catalyzed directed sp3-C-H borylation reactions.10h,10j
Si
O
Me
O
Me
Si
O
Si
O
Si
Si
O
O
O
Si
O
O
O
O
Si
O
Si
O
O
O
O
O
Si
O
O
O
SiO2
SiO2
SiO2
Silica-3p-TPP, 95% (80%)
Silica-SMAP, 81%
Silica-TRIP, 98%
P
Me
P
Me
O
Me
Me
Si
Me
Me
Me
Si
O
Si
O
Si
Me
Me
Me
Si
O
O
Si
O
O
Me
Si
O
O
Me
Si
O
O
O
Si
O
O
Si
O
O
O
O
Si
O
O
O
Si
O
O
SiO2
SiO2
O
Silica-3p-TBP, 88%
Silica-3m-TPP, 92%
P
Ph2P
Ph
PPh2
Me
Me
Si
Me
O
O
Me
Me
Me
Me
O
Si
O
Me
O
Si
O
Si
O
Si
O
O
O
Si
O
O
Si
O
O
Si
O
SiO2
O
SiO2
SiO2
Silica-2p-TPP, 70%
Silica-1p-TPP, 48%
Silica-1p-EtTPP, 16%
none, 0%
P
SiMe2(OiPr)
PPh3, 0%
3
3p-TPP, 0%
Herein, we report that silica-supported tripod triarylphos-
phine ligands such as Silica-3p-TPP enabled Pd-catalyzed
borylation of chloroarenes under mild conditions. The hetero-
geneous Pd system based on Silica-3p-TPP was applicable to
one-pot biaryl synthesis via the Miyaura borylation-Suzuki-
Miyaura coupling sequence.
Figure 1. Ligand effects in Pd-catalyzed borylation of 1a with
2. Conditions: 1a (0.5 mmol), 2 (0.55 mmol), [PdCl(η3-cin-
namyl)]2 (0.00125 mmol, 0.5 mol % Pd), ligand ([P] 0.07-
0.11 mmol g¹1, 0.005 mmol, 1 mol % P), KOAc (1.5 mmol),
benzene (1 mL), 25 °C, 10 h. Yields were determined by
1H NMR analysis. The isolated yield is given in parenthesis.
Various immobilized phosphines were evaluated for the
ligand performance in the Pd-catalyzed borylation of p-chloro-
toluene (1a, 0.5 mmol) with bis(pinacolato)diboron (2,
0.55 mmol) at 25 °C for 10 h in the presence of KOAc
(1.5 mmol) as a base. Pd catalysts were prepared in situ from
[PdCl(η3-cinnamyl)]2 (0.5 mol % Pd) and the phosphine ligands
(Pd/P 1:2). The results are summarized in Figure 1. Notably,
4,4¤-dimethylbiphenyl, a potential by-product due to the cou-
pling between 1a and borylation product 3a, was not formed
under the conditions using the mild base KOAc. Interestingly,
the triptycene-type ligand Silica-TRIP was more effective than
Silica-SMAP inspite of its lower electron-donating ability as
a triarylphosphine (98% yield).14 Among the silica-supported
tripod triarylphosphines with different backbone structures
(Silica-3p-TPP, Silica-3m-TPP,15 and Silica-3p-TBP15), Silica-
3p-TPP was the most efficient, causing a high conversion of 1a
into 3a.16,17 The mono-P-ligating features of the silica-supported
ligands would assist oxidative addition of the C-Cl bond to the
Pd0-P species. The enhanced ligand performances of the Silica-
TRIP and Silica-3p-TPP triarylphosphines over the Silica-
SMAP trialkylphosphine suggest the importance of transmeta-
lation and reductive elimination steps in these catalytic systems.
Silica-3p-TPP is advantageous over Silica-TRIP in terms of the
ease in preparation.
The heterogeneous catalysts were easily separated from the
products by filtration, and inductively coupled plasma atomic
emission spectroscopy (ICP-AES) analysis of the filtrate
584 | Chem. Lett. 2014, 43, 584–586 | doi:10.1246/cl.131161
© 2014 The Chemical Society of Japan

Table 1. Borylation of various chloroarenes 1 with 2a
[PdCl(η3-cinnamyl)]2
(Pd: 1 mol %)
O
Cl
[PdCl(η3-cinnamyl)]2
1a
Silica-3p-TPP
(Pd/P 1:2)
Me
(0.5 mmol)
(Pd: 0.5 mol %)
Silica-3p-TPP (Pd/P 1:2)
O
1d (0.5 mmol)
O
O
O
O
Me
+
+
Cl
1 (0.5 mmol)
B B
Bpin
K3PO4 (1.5 mmol)
benzene/H2O
(1 + 0.1 mL)
KOAc (1.5 mmol)
benzene (1 mL)
25 °C, 10 h
Me
R
R
2
KOAc (1.5 mmol)
4
(0.5 mmol)
solvent, temp., 10 h
2 (0.55 mmol)
3
74% (isolated)
in two steps
60 °C, 10 h
Chloroarene
Temp.
/°C
Product
Yieldb
/%
Entry
Solvent
1
2
Scheme 1. One-pot biaryl synthesis combining Miyaura
borylation and Suzuki-Miyaura coupling.
MeO
Cl
MeO
Bpin
1c
2
benzene
benzene
benzene
25
25
25
91 (66)
99 (79)
95 (74)
1b
3b
quantitatively borylated at 25 °C with 0.5 mol % catalyst loading
(Entries 2-4). Pd catalysis (1 mol % Pd, 60 °C) was applicable to
the borylation of heteroaryl chlorides 1f and 1g to afford the
corresponding heteroaryl boronates 3f and 3g in good to high
yields (Entries 5 and 6). o-Chlorotoluene (1h) reacted at 60 °C
to give 3h in quantitative yield (Entry 7). The Pd-Silica-3p-
TPP system was capable of converting the more challenging
substrates 2,6-dimethylchlorobenzene (1i) and 2,4,6-triethyl-
chlorobenzene (1j) into sterically congested arylboronates 3i and
3j, respectively, under relatively mild conditions with reason-
able catalyst loading (Entries 8 and 9). However, the reaction of
these sterically demanding substrates proceeded under milder
conditions with the more compact Silica-SMAP ligand.9
The efficacy of the tripod phosphine-based catalyst systems
for the Miyaura borylation and the Suzuki-Miyaura coupling
with chloroarenes allows the one-pot synthesis of an unsym-
metrical biaryl from two different chloroarenes as shown in
Scheme 1. The substrates for the borylation reaction 1a and 2
were mixed together in benzene with KOAc (1a/2/KOAc 1:1:3)
in the presence of the Pd-Silica-3p-TPP catalyst (1 mol % Pd,
Pd/P 1:2), and the mixture was stirred at 25 °C for conversion to
3a (10 h). To this mixture, chloroarene 1d (1 equiv) dissolved in
benzene and aq. K3PO4 (3 equiv) were added, and the mixture
was stirred at 60 °C for 10 h. After removal of solids, silica gel
chromatography afforded the unsymmetrical biaryl 4 in 74%
yield.
In summary, a silica-supported tripod triarylphosphine
(Silica-3p-TPP) having a Ph3P-type core tripodally immobilized
on silica gel enabled the Pd-catalyzed borylation of chloroarenes
under mild conditions inspite of the moderate electron-donating
and steric properties. Various chloroarenes substituted with
electron-donating and electron-withdrawing groups were suc-
cessfully converted into the corresponding arylboronates in high
yields. The heterogeneous Pd catalyst system is applicable to
one-pot biaryl synthesis from a pair of chloroarenes through
the Miyaura borylation-Suzuki-Miyaura coupling sequence.
Further catalytic application of silica-supported tripod triaryl-
phosphines as a ligand is currently under investigation.
F3C
O
Cl
F3C
O
Bpin
3c
1c
Bpin
Cl
3
Me
O
Me
O
1d
3d
Bpin
Cl
4
benzene
25
99 (60)
99 (65)
83 (49)
MeO
MeO
1e
3e
5c
6c
1,4-dioxane 60
1,4-dioxane 60
Cl
Bpin
1f
3f
S
S
Cl
1g
Bpin
3g
N
N
Me
Me
Me
Me
7
8
benzene
benzene
60
80
99 (89)
87 (80)
Bpin
3h
Cl
1h
Cl
Bpin
3i
Me
Et
Me 1i
Et
Et
Cl
Et
Bpin
9
toluene
90
74d (70)
Et
1j
Et
3j
aConditions:
1
(0.5 mmol), 2
(0.55 mmol), [PdCl(η3-cin-
namyl)]2 (0.00125 mmol, 0.5 mol % Pd), Silica-3p-TPP ([P]
0.11 mmol g¹1, 0.005 mmol, 1 mol % P), KOAc (1.5 mmol),
solvent (1 mL), 25-90 °C, 10 h. bYields were determined by
1H NMR analysis. The isolated yields are given in parentheses.
c[PdCl(η3-cinnamyl)]2 (0.0025 mmol, 1 mol % Pd). d1,3,5-
Triethylbenzene (17%) was detected in the crude mixture.
indicated that the Pd leaching was below the detection limit
(0.02% of the loaded Pd). Unfortunately, attempts to reuse the
catalyst were unsuccessful.
The bipod and monopod phosphines (Silica-2p-TPP,11
Silica-1p-TPP,11 and Silica-1-EtTPP11) were also effective, but
were significantly less efficient than the tripod phosphines,
affording 3a in only 70%, 48%, and 16% yields, respectively
(Figure 1). No reaction occurred with the soluble phosphine
ligands such as 3p-TPP11 and Ph3P or under the phosphine-free
conditions.
This work was supported by Grants-in-Aid for Scientific
Research on Innovative Areas “Reaction Integration” (MEXT)
and ACT-C (JST) to M.S. and by Grant-in-Aid for Young
Scientists (B) from JSPS to T.I.
The borylation protocol using the Pd-Silica-3p-TPP catalyst
system was applied to the reaction of various chloroarenes.
Results are summarized in Table 1. p-Chloroanisole (1b), which
has an electron-donating MeO substituent, was somewhat less
reactive than the electronically unbiased substrate 1a, but the
borylation of 1b with 1 mol % catalyst loading proceeded
smoothly at 25 °C to afford 3b in 91% yield (Entry 1). The
chloroarenes with electron-withdrawing para-substituents such
as CF3 (1c), MeCO (1d), and MeO2C (1e) groups were
References and Notes
1
For reviews on application of arylboronic acid derivatives,
see: a) Boronic Acids: Preparation and Applications in
Organic Synthesis and Medicine, ed. by D. G. Hall, Wiley-
VCH, 2005. doi:10.1002/3527606548. b) N. Miyaura, Bull.
Chem. Soc. Jpn. 2008, 81, 1535.
Chem. Lett. 2014, 43, 584–586 | doi:10.1246/cl.131161
© 2014 The Chemical Society of Japan | 585

2
3
T. Ishiyama, M. Murata, N. Miyaura, J. Org. Chem. 1995,
60, 7508.
For a recent review: W. K. Chow, O. Y. Yuen, P. Y. Choy,
C. M. So, C. P. Lau, W. T. Wong, F. Y. Kwong, RSC Adv.
2013, 3, 12518.
For references on the metal-catalyzed borylation of chloro-
arenes at room temperature, see: For Pd-catalyzed coupling:
a) K. L. Billingsley, T. E. Barder, S. L. Buchwald, Angew.
Chem., Int. Ed. 2007, 46, 5359. For Ni-catalyzed coupling,
see: b) G. A. Molander, L. N. Cavalcanti, C. García-García,
J. Org. Chem. 2013, 78, 6427.
For selected references with Pd-catalyzed borylation of
chloroarenes, see: a) T. Ishiyama, K. Ishida, N. Miyaura,
Tetrahedron 2001, 57, 9813. b) A. Fürstner, G. Seidel, Org.
Lett. 2002, 4, 541. c) M. Murata, T. Sambommatsu, S.
Watanabe, Y. Masuda, Synlett 2006, 1867. d) G. A.
Molander, S. L. J. Trice, S. D. Dreher, J. Am. Chem. Soc.
2010, 132, 17701. e) W. K. Chow, O. Y. Yuen, C. M. So,
W. T. Wong, F. Y. Kwong, J. Org. Chem. 2012, 77, 3543.
For selected references on metal-catalyzed borylations of
aryl mesylates and tosylates, see: For Pd-catalyzed coupling:
a) W. K. Chow, C. M. So, C. P. Lau, F. Y. Kwong, Chem.®
Eur. J. 2011, 17, 6913. For Ni-catalyzed coupling: b) D. A.
Wilson, C. J. Wilson, C. Moldoveanu, A.-M. Resmerita, P.
Corcoran, L. M. Hoang, B. M Rosen, V. Percec, J. Am.
Chem. Soc. 2010, 132, 1800.
Recently, transition-metal-catalyst-free borylation of aryl
halides with silylborane/base or borylzincate systems were
reported. These reactions, however, showed no or only a low
efficiency for the reaction of chloroarenes. See: a) E.
Yamamoto, K. Izumi, Y. Horita, H. Ito, J. Am. Chem. Soc.
2012, 134, 19997. b) Y. Nagashima, R. Takita, K. Yoshida,
K. Hirano, M. Uchiyama, J. Am. Chem. Soc. 2013, 135,
18730.
H. Ohmiya, M. Sawamura, Organometallics 2008, 27, 6495.
c) S. Kawamorita, H. Ohmiya, K. Hara, A. Fukuoka, M.
Sawamura, J. Am. Chem. Soc. 2009, 131, 5058. d) S.
Kawamorita, H. Ohmiya, M. Sawamura, J. Org. Chem.
2010, 75, 3855. e) K. Yamazaki, S. Kawamorita, H. Ohmiya,
M. Sawamura, Org. Lett. 2010, 12, 3978. f) S. Kawamorita,
T. Miyazaki, H. Ohmiya, T. Iwai, M. Sawamura, J. Am.
Chem. Soc. 2011, 133, 19310. g) S. Kawamorita, K.
Yamazaki, H. Ohmiya, T. Iwai, M. Sawamura, Adv. Synth.
Catal. 2012, 354, 3440. h) S. Kawamorita, R. Murakami, T.
Iwai, M. Sawamura, J. Am. Chem. Soc. 2013, 135, 2947.
i) S. Konishi, S. Kawamorita, T. Iwai, P. G. Steel, T. B.
Marder, M. Sawamura, Chem.®Asian J. 2014, 9, 434. See
also ref 9. For the synthesis and applications of Silica-TRIP,
see: j) S. Kawamorita, T. Miyazaki, T. Iwai, H. Ohmiya, M.
Sawamura, J. Am. Chem. Soc. 2012, 134, 12924. See also
ref 10f.
4
5
11 T. Iwai, R. Tanaka, T. Harada, M. Sawamura, Chem.®Eur. J.
2014, 20, 1057.
6
7
12 T. Iwai, T. Harada, K. Hara, M. Sawamura, Angew. Chem.,
Int. Ed. 2013, 52, 12322.
13 For a heterogeneous Pd catalyst system based on a polymeric
imidazole support that showed high activity for the Suzuki-
Miyaura coupling between chloroarenes and arylboronic
acids in water, see: Y. M. A. Yamada, S. M. Sarkar, Y.
Uozumi, J. Am. Chem. Soc. 2012, 134, 3190.
14 For selected references on employing triarylphosphines in
the Pd-catalyzed cross-coupling of chloroarenes, see: a) H.
Ohta, M. Tokunaga, Y. Obora, T. Iwai, T. Iwasawa, T.
Fujihara, Y. Tsuji, Org. Lett. 2007, 9, 89. b) T. Fujihara, S.
Yoshida, H. Ohta, Y. Tsuji, Angew. Chem., Int. Ed. 2008, 47,
8310. See also refs 5e, 11, 12.
15 Supporting Information for the preparation and character-
ization of Silica-3m-TPP and Silica-3p-TBP is available
electronically on the CSJ-Journal Web site, http://www.
csj.jp/journals/chem-lett/index.html.
16 The threefold crosslinked polystyrene-Ph3P hybrid PS-
Ph3P12 did not produce an active catalyst. The access of
the insoluble base (KOAc) to the catalytic center seems to be
inefficient.18
8
9
Transition-metal-catalyzed C-H borylation of arenes is also
a useful method to prepare aryl boronates. See: I. A. I.
Mkhalid, J. H. Barnard, T. B. Marder, J. M. Murphy, J. F.
Hartwig, Chem. Rev. 2010, 110, 890.
S. Kawamorita, H. Ohmiya, T. Iwai, M. Sawamura, Angew.
Chem., Int. Ed. 2011, 50, 8363.
10 Silica-SMAP and Silica-TRIP can be purchased from Wako
Pure Chemical Industries, Ltd. For the synthesis and
applications of Silica-SMAP, see: a) G. Hamasaka, A.
Ochida, K. Hara, M. Sawamura, Angew. Chem., Int. Ed.
2007, 46, 5381. b) G. Hamasaka, S. Kawamorita, A. Ochida,
R. Akiyama, K. Hara, A. Fukuoka, K. Asakura, W. J. Chun,
17 The Pd-Silica-3p-TPP catalyst system in dioxane as a
solvent also provided the product 3a in 94% yield, while
the reaction did not proceed at all in DMSO under otherwise
identical conditions.
18 M. Sumimoto, N. Iwane, T. Takahama, S. Sakaki, J. Am.
Chem. Soc. 2004, 126, 10457. See also ref 4a.
586 | Chem. Lett. 2014, 43, 584–586 | doi:10.1246/cl.131161
© 2014 The Chemical Society of Japan