An efficient catalyst system for palladium-catalyzed borylation of aryl halides with pinacolborane

Article abstract of DOI:10.1055/s-2006-947365

The combination of Pd(dba)₂ and bis(2-di-tert-butyl- phosphinophenyl)ether has proven to be efficient for the cross-coupling of pinacolborane with aryl bromides and chlorides. The substrate scope is broad and the present system enables the synthesis of ortho-, meta-, and para-substituted electron-rich and -deficient arylboronates. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-947365

LETTER
1867
An Efficient Catalyst System for Palladium-Catalyzed Borylation of Aryl
Halides with Pinacolborane
P
M
alladium(0)-Catalyze
i
d
Bory
k
i
l
Halides Murata,* Tomoko Sambommatsu, Shinji Watanabe, Yuzuru Masuda
Department of Materials Science, Kitami Institute of Technology, Kitami 090-8507, Japan
Fax +81(157)264973; E-mail: muratamk@mail.kitami-it.ac.jp
Received 25 April 2006
poor yields, and no example of the borylation of aryl
chlorides was provided. In this paper, we wish to report a
general protocol for the palladium-catalyzed borylation of
Abstract: The combination of Pd(dba)2 and bis(2-di-tert-butyl-
phosphinophenyl)ether has proven to be efficient for the cross-
coupling of pinacolborane with aryl bromides and chlorides. The
substrate scope is broad and the present system enables the synthe- aryl halides 2 using 1. The present catalyst system using a
sis of ortho-, meta-, and para-substituted electron-rich and -defi- bulky and electron-rich bis-phosphine ligand overcomes
cient arylboronates.
many limitations of the previous methods.
Key words: boron, palladium, catalysis, cross-coupling, ligands
An initial screening was performed using several phos-
phine ligands L1–L8 (Figure 1) for the coupling reaction
of 1 and ethyl 4-bromobenzoate (2a). These results are
Arylboronic acids and their esters are useful intermediates summarized in Table 1. The treatment of 2a (1 equiv)
in organic synthesis, particularly with reactions involving with 1 (2 equiv) and Et N (3 equiv) in the presence of
3
carbon–carbon bond formation through the palladium- 5 mol% of Pd(dba) and the phosphine ligand (Pd:P = 1:2)
2
1
catalyzed Suzuki–Miyaura cross-coupling reaction. Var- in dioxane at 80 °C was found to lead to the corresponding
ious methods are now available for their preparation. arylboronate 3a. The formation of ethyl benzoate (4a) by
Above all, the palladium-catalyzed cross-coupling reac- reduction of the starting 2a was the major side reaction.
2
3–8
tions of tetra(alkoxo)diborons or dialkoxyboranes with For the electron-deficient 2a, the use of ligands L1, DPPF
organic electrophiles have emerged as a general and (L3), and DPEphos (L6), which have been utilized for the
powerful method for carbon–boron bond formation. The borylation of aryl iodides and electron-rich aryl bromides,
borylation using dialkoxyborane, such as pinacolborane did not provide the desired product 3a as expected (entries
3
,5,8
(
1), is an atom-economical method, more economically 1, 3, 6).
Recently, it has been revealed that DiPPF
9
10
profitable as 1, and cheaper than bis(pinacolato)diboron. (L4) and DtBPF (L5) were effective ligands for other
We demonstrated the first examples of the palladium-cat- palladium-catalyzed carbon–heteroatom bond forming
alyzed borylation of aryl halides 2 with 1 to provide aryl- processes. Bearing these reports in mind, we postulated
boronates 3 (Equation 1). Although our original that bis-phosphines having dialkylphosphino groups to-
procedure using PdCl (dppf) was found to work effective- gether with large bite angles created by backbones, such
3
2
ly for most aryl iodides, aryl bromides were often prob- as L4 and L5, could be efficient supporting ligands for the
lematic with undesirable reduced arenes 4. Recently, the borylation. We then examined the chelating alkylphos-
5
8
Buchwald phosphine ligand and DPEphos have been phines. Employing L4 and i-Pr-DPEphos (L7), however,
utilized as efficient supporting ligands for the palladium- gave poor yields of 3a due to the extensive formation of
catalyzed borylation of aryl bromides. Whereas the scope 4a (entries 4 and 7). Among the many trials using elec-
of the aryl halides 2 in the palladium-catalyzed borylation tron-rich and sterically hindered bidentate phosphines, we
has been improved, these catalyst systems still had some were pleased to observe that the use of t-Bu-DPEphos
drawbacks, for example the reactions of electron-deficient (L8) remarkably improved the yield and selectivity,
or ortho,ortho¢-disubstituted bromides produced only although the formation of 4a could not be completely
suppressed (entry 8).11
Pd catalyst
Et3N
PR2
PinB
H
+
X
Ar
PinB Ar
+
H
Ar
R = Cy L1
t-Bu L2
R = Ph L3
i-Pr L4
dioxane
Fe
1
2
3
4
t-Bu L5
PR2
PR2
O
PinB =
B
PR2
O
PR2
O
R = Ph L6
i-Pr L7
Equation 1 Palladium-catalyzed borylation using pinacolborane
t-Bu L8
SYNLETT 2006, No. 12, pp 1867–1870
Advanced online publication: 24.07.2006
0
1
.0
8
.2
0
0
6
Figure 1 Phosphine ligands
DOI: 10.1055/s-2006-947365; Art ID: U05006ST
©
Georg Thieme Verlag Stuttgart · New York

1
868
M. Murata et al.
LETTER
Table 1 Screening of Ligands for Borylation of Ethyl 4-Bromo-
benzoate (2a)
borylation using 1. The present catalyst system also
proved to be highly efficient for the electron-rich aryl
chlorides 2j and 2k, although the reaction temperature of
a
Entry
Ligand
Yield (%)b
1
20 °C was required (entries 9 and 10). To the best of our
3
a
0
6
0
4a
0
knowledge, this is the first example of the selective
borylation of aryl chlorides with 1. However, several at-
tempts at the borylation of the electron-deficient aryl
chloride 2l were unsuccessful as the presence of electron-
withdrawing substituents remarkably increased the yield
of 4a (entry 11).
1c
L1
2c
3
4
5
6
7
L2
44
40
80
15
46
62
16
L3, DPPF
L4, DiPPF
L5, DtBPF
L6, DPEphos
L7, i-Pr-DPEphos
L8, t-Bu-DPEphos
11
75
0
To verify the feasibility of the reaction on a common
laboratory scale, the borylation of 2a was repeated on a 5-
mmol scale (see the experimental section). In this case,
the amounts of 1, the catalyst, and the solvent were low-
ered. The reducing the amount of the reagents would be
desirable to limit the amount of waste generation from this
procedure, especially if the borylation was performed on
a preparative scale. Actually, the present system was
applied to the larger scale synthesis of 3a without any
difficulty.
15
84
8
a
Reaction conditions: 2a (0.5 mmol), 1 (1.0 mmol), Et N (1.5 mmol),
3
Pd(dba) (25 mmol), ligand (25 mmol), in dioxane (2 mL) at 80 °C
2
for 6 h.
b
GC yields are based on 2a.
c
In conclusion, we have developed a general method for
the borylation of aryl halides 2 with pinacolborane 1 using
50 mmol of phosphine ligand was used.
Pd(dba) /t-Bu-DPEphos (L8) as the catalyst. The
2
substrate scope was significantly broad and included
electron-deficient and sterically hindered aryl bromides
and electron-rich aryl chlorides. This catalyst system has
the widest substrate scope of any reported to date. Further
investigations to broaden the scope of the organic electro-
philes are currently underway in our laboratory.
After optimization of the reaction conditions, we investi-
gated the scope of the borylation of the aryl halides 2 us-
ing 1. These results are presented in Table 2. For all the
cases listed in Table 2, small amounts of reduced by-prod-
ucts 4 were produced, but their isolation was very easy.
The present process was extremely tolerant of a variety of
common functional groups. Thus, the presence of func-
tional groups, such as an ester (Table 1), ketone carbonyl
Palladium-Catalyzed Borylation of Aryl Halides; General
Procedure (Table 1 and Table 2)
(
4
Table 2, entry 2), cyano (entry 3), and nitro groups (entry
), in the starting 2 did not interfere with the outcome of
In a glove box, Pd(dba) (25 mmol) and t-Bu-DPEphos (L8, 25
2
the present reaction. The use of the catalyst derived from mmol) were placed in a screw-capped vial, and dissolved in 2 mL of
Pd(dba) and L8 demonstrated a good deal of generality, 1,4-dioxane. After being stirred for 30 min, Et N (1.5 mmol), the
2
3
aryl halide 2 (0.50 mmol), and pinacolborane (1, 1.0 mmol) were
successively added. The vial was sealed with a cap and removed
from the glove box. The reaction mixture was then stirred at 80–
and the differences in the yields among the electronic
characteristics of the substituent on the aryl bromides 2
(
X = Br) were not particularly large. In addition, the
1
00 °C for 6 h. After the reaction, the mixture was diluted with
sterically hindered bromides 2g–i also gave the corre-
sponding arylboronates 3 in high yields (entries 6–8). It is
Et O, washed with brine, and dried over Na SO . The solvent was
2
2
4
removed under reduced pressure, and the residue was purified by
noteworthy that the reactions of the ortho,ortho¢-disub- Kugelrohr distillation to give the desired arylboronate 3. The prod-
3
5
1
stituted bromides 2h and 2i, which were problematic sub- ucts 3a–c, 3e and 3h were identified by comparison of their H
5
,8
NMR data with those reported in the literature. Other boronates
d,f,g,i,j were characterized by H NMR and C NMR spectrosco-
py and HRMS analysis.
strates in previous catalyst systems, proceeded in high
yields (entries 7 and 8). The present system enables the
synthesis of ortho-, meta-, and para-substituted electron-
rich and -deficient arylboronates 3 from the correspond-
ing bromides 2.
1
13
3
1
3
Large-Scale Preparation of Arylboronates; General Procedure
A flask with a septum inlet was charged with Pd(dba) (28 mg, 0.05
2
mmol), L8 (25 mg, 0.05 mmol), and a magnetic stirring bar, and
Although aryl chlorides are less reactive for the palladi-
um-catalyzed processes than their bromide and iodide
counterparts, these substrates are often more readily
available from commercial sources and less expensive.12
then flushed with nitrogen. Dioxane (10 mL), Et N (2.0 mL, 14
3
mmol), 2a (1.14 g, 4.97 mmol), and 1 (0.87 mL, 6 mmol) were add-
ed by syringe. After being stirred for 16 h at 80 °C, the mixture was
extracted with Et O (10 mL). The extract was washed with brine (10
2
Thus, we then turned our attention toward the application mL), dried over Na SO , and concentrated. The residue was purified
2
4
of aryl chlorides 2 (X = Cl) for the palladium-catalyzed by Kugelrohr distillation to give 1.11 g (81% yield) of 3a.
Synlett 2006, No. 12, 1867–1870 © Thieme Stuttgart · New York

LETTER
Palladium(0)-Catalyzed Borylation of Aryl Halides
1869
Table 2 Palladium-Catalyzed Borylation of Representative 2 with 1
Entry
Aryl Halide 2
Product 3
Condition
Yield (%)a
91
Br
OMe
Ac
PinB
OMe
Ac
1
100 °C, 6 h
2
b
3b
Br
PinB
3c
2
3
80 °C, 6 h
80 °C, 6 h
78
79
2
c
Br
PinB
CN
CN
2
d
3d
Br
NO2
CF3
PinB
3e
NO2
4
5
80 °C, 2 h
80 °C, 6 h
76
82
2
e
Br
PinB
CF3
2
f
3f
Ph
Ph
6
7
100 °C, 6 h
100 °C, 6 h
86
82
Br
PinB
2
g
3g
Me
Me
Br
PinB
Me
Me
3h
2
h
i-Pr
i-Pr
Br
i-Pr
PinB
i-Pr
8
9
100 °C, 6 h
72
i-Pr
i-Pr
2
i
3i
Cl
NHMe
OMe
PinB
NHMe
120 °C, 24 h
120 °C, 24 h
81
86
2
j
3j
1
1
0
1
Cl
3
b
2
k
Cl
CO2Et
3a
120 °C, 24 h
10b
2
l
a
Isolated yields are based on 2.
GC yield. The GC analysis also indicated the formation of 4a in 87% yield.
b
Synlett 2006, No. 12, 1867–1870 © Thieme Stuttgart · New York

1
870
M. Murata et al.
LETTER
References and Notes
(12) For a review of the palladium-catalyzed couplings of aryl
chlorides, see: Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed.
(
1) For reviews of the Suzuki coupling, see: (a) Miyaura, N.;
Suzuki, A. Chem. Rev. 1995, 95, 2457. (b) Miyaura, N.
Adv. Organomet. Chem. 1998, 6, 187. (c) Miyaura, N. Top.
Curr. Chem. 2002, 219, 11.
2
002, 41, 4176.
1
(
13) Compound 3d: H NMR (CDCl ): d = 1.35 (s, 12 H), 7.47 (t,
3
J = 7.9 Hz, 1 H), 7.73 (d, J = 7.9 Hz, 1 H), 8.01 (d, J = 7.9
13
Hz, 1 H), 8.09 (s, 1 H). C NMR (CDCl ): d = 24.81, 84.46,
3
(
(
(
2) For reviews of the Miyaura borylation, see: (a) Ishiyama,
111.95, 118.79, 128.36, 134.37, 138.37, 138.73. HRMS
T.; Miyaura, N. J. Organomet. Chem. 2000, 611, 392.
+
(
EI): m/z calcd for C H BNO [M ]: 229.1274; found:
13 16 2
(
b) Ishiyama, T.; Miyaura, N. Chem. Rec. 2004, 3, 271.
3) (a) Murata, M.; Watanabe, S.; Masuda, Y. J. Org. Chem.
997, 62, 6458. (b) Murata, M.; Oyama, T.; Watanabe, S.;
–1
229.1312. IR (KBr): 2228 cm .
1
Compound 3f: H NMR (CDCl ): d = 1.36 (s, 12 H), 7.61 (d,
J = 7.9 Hz, 2 H), 7.92 (d, J = 7.9 Hz, 2 H). C NMR
3
1
13
Masuda, Y. J. Org. Chem. 2000, 65, 164.
(
CDCl ): d = 24.98, 84.25, 124.29 (q, J = 4 Hz), 124.13 (q,
3
4) (a) Murata, M.; Watanabe, S.; Masuda, Y. Tetrahedron Lett.
J = 272 Hz), 132.80 (q, J = 32 Hz), 135.21. HRMS (EI):
m/z calcd for C H BF O [M ]: 272.1196; found:
2000, 41, 5877. (b) Murata, M.; Oyama, T.; Watanabe, S.;
+
1
3
16
3
2
Masuda, Y. Synthesis 2000, 778. (c) Murata, M.; Oyama,
T.; Watanabe, S.; Masuda, Y. Synth. Commun. 2002, 32,
2
72.1229.
1
Compound 3g: H NMR (CDCl ): d = 1.21 (s, 12 H), 7.30–
3
2
513.
5) Baudoin, O.; Guénard, D.; Guéritte, F. J. Org. Chem. 2000,
5, 9268.
6) Doux, M.; Mézailles, N.; Melaimi, M.; Ricard, L.; LeFloch,
P. Chem. Commun. 2002, 1566.
13
7.50 (m, 8 H), 7.71 (d, J = 7.8 Hz, 1 H). C NMR (CDCl ):
3
(
(
(
(
(
d = 24.55, 83.69, 126.23, 126.79, 127.74, 128.92, 129.08,
6
1
30.03, 134.40, 143.19, 147.46. HRMS (EI): m/z calcd for
+
C H BO [M ]: 280.1635; found: 280.1629.
Compound 3i: H NMR (CDCl ): d = 1.21 (d, J = 6.7 Hz, 6
H), 1.25 (d, J = 6.7 Hz, 12 H), 1.37 (s, 12 H), 2.84 (sept,
1
8
21
2
1
3
7) Wolan, A.; Zaidlewicz, M. Org. Biomol. Chem. 2003, 1,
3274.
J = 6.7 Hz, 1 H), 2.98 (sept, J = 6.7 Hz, 2 H), 6.93 (s, 2 H).
8) Broutin, P.-E.; Čerña, I.; Campaniello, M.; Leroux, F.;
Colobert, F. Org. Lett. 2004, 6, 4419.
9) Murata, M.; Buchwald, S. L. Tetrahedron 2004, 60, 7397.
13
C NMR (CDCl ): d = 24.01, 24.55, 24.98, 34.00, 34.49,
3
83.61, 119.63, 149.72, 151.86. HRMS (EI): m/z calcd for
+
C H BO [M ]: 330.2730; found: 330.2773.
Compound 3j: H NMR (CDCl ): d = 1.32 (s, 12 H), 2.86 (d,
J = 5.5 Hz, 3 H), 3.92 (br s, 1 H), 6.58 (d, J = 8.5 Hz, 2 H),
2
1
35
2
(
10) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120,
369.
11) t-Bu-DPEphos (L8) was prepared from diphenylether and
t-Bu) PCl by a similar procedure for the preparation of
1
3
7
(
13
7
.65 (d, J = 8.5 Hz, 2 H). C NMR (CDCl ): d = 24.79,
3
(
2
30.22, 83.13, 111.38, 136.26, 151.74. HRMS (EI): m/z calcd
DPEphos. See: Kranenburg, M.; Vanderburgt, Y. E. M.;
Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Goubitz, K.;
Fraanje, J. Organometallics 1995, 14, 3081.
+
for C H BNO [M ]: 233.1587; found: 233.1611.
IR (KBr): 3425, 3401, 3375 cm .
1
3
20
2
–1
Synlett 2006, No. 12, 1867–1870 © Thieme Stuttgart · New York