Palladium- or nickel-catalyzed coupling reaction of dialkoxyboranes with chloroarenes: arylation of 1,3,2-dioxaborolanes or l,3,2-dioxaborinanes

Article abstract of DOI:10.3987/COM-09-S(S)63

The borylation of electron-deficient aryl chlorides with pinacolborane proceeded in the presence of BU₄NI and a catalytic amount of Pd(dba)₂ / bis(2-di-tert-butylphosphinophenyl) ether. The combination of NiCl2(dppp) catalyst and Bu₄NBr was also efficient for the borylation of aryl chlorides.

Full text of DOI:10.3987/COM-09-S(S)63

HETEROCYCLES, Vol. 80, No. 1, 2010
213
HETEROCYCLES, Vol. 80, No. 1, 2010, pp. 213 - 218. © The Japan Institute of Heterocyclic Chemistry
Received, 21st July, 2009, Accepted, 18th August, 2009, Published online, 21st August, 2009
DOI: 10.3987/COM-09-S(S)63
PALLADIUM- OR NICKEL-CATALYZED COUPLING REACTION OF
DIALKOXYBORANES WITH CHLOROARENES: ARYLATION OF
1,3,2-DIOXABOROLANES OR 1,3,2-DIOXABORINANES†
Miki Murata,* Tomoko Sambommatsu, Takeshi Oda, Shinji Watanabe, and
Yuzuru Masuda
Department of Materials Science and Engineering, Kitami Institute of
Technology, 165 Koencho, Kitami 090-8507, Japan
E-mail: muratamk@mail.kitami-it.ac.jp
Abstract – The borylation of electron-deficient aryl chlorides with pinacolborane
proceeded in the presence of Bu4NI and a catalytic amount of Pd(dba)2 /
bis(2-di-tert-butylphosphinophenyl) ether. The combination of NiCl2(dppp)
catalyst and Bu4NBr was also efficient for the borylation of aryl chlorides.
Arylboronic acids and their esters are versatile reagents for modern organic synthesis, particularly with
reactions involving carboncarbon bond formation through the Suzuki-Miyaura cross-coupling reaction.1
The versatility of this methodology renders arylboronates attractive targets for synthesis. In recent years,
the palladium-catalyzed borylation of aryl electrophiles with bis(pinacolato)diboron2 or
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (pinacolborane, 1a)37 has proved to be a general and powerful
method for carbonboron bond formation. In particular, 1a is a cheaper and more atom-economical boron
source. Although numerous catalyst systems have been reported to affect the borylation using 1a, the use
of aryl iodides or bromides is often necessary. Despite several advantages of employing aryl chlorides 2,
examples of the borylation of 2 with 1a are rare.8 We demonstrated the first examples of the
palladium-catalyzed borylation of 2; however, this method was only applicable to aryl chlorides having
electron-donating groups at para-position.6 Thereafter, the scope of 2 in the palladium-catalyzed
borylation was somewhat improved by Buchwald and his colleague.7 However, there has been no
successful report of the borylation of aryl chlorides having electron-withdrawing groups on the aromatic
rings. In this paper, we wish to report an efficient protocol for the transition-metal-catalyzed borylation of
† This paper is dedicated to Professor Akira Suzuki on the occasion of his 80th birthday.

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HETEROCYCLES, Vol. 80, No. 1, 2010
electron-deficient aryl chlorides 2 using cyclic dialkoxyboranes 1 (Scheme 1).
catalyst / Bu4NX
O
O
O
O
Et3N
B
H
Cl
B
H
+
+
dioxane
100 °C
EWG
EWG
EWG
1
2
3
4
Me
Me
(1a),
Me
Me
Me
Me
O
O
O
B H
B H
catalyst / Bu NX :
Pd(dba)2 / t-Bu-DPEphos / Bu4NI
1 :
(1b)
4
O
or NiCl2(dppp) / Bu4NBr
Me
Scheme 1. Borylation of Electron-Deficient Aryl Chlorides
As a test for the optimization of reaction parameters, 1a and ethyl 4-chlorobenzoate (2a) were selected as
reaction partners. The results are summarized in Table 1. The borylation of such an electron-deficient aryl
chloride using Pd(dba)2 and bis(2-di-tert-butylphosphinophenyl) ether (t-Bu-DPEphos) as a catalyst gave
only 13% yield of the borylated product 3a due to a strong tendency to produce the reduced arene 4a
(entry 1).6 Recently, we reported that addition of an iodide anion source improved the selectivity on the
analogous silylation of aryl halides with hydrosilanes.9 We then examined a treatment with additional 2
equiv of tetrabutylammonium halides, and found that the borylation proceeded selectively in the presence
of Bu4NI (entry 2). Bu4NBr or Bu4NCl was less effective (entries 3 and 4). Although the mechanism for
this borylation is unclear at the present stage, the role of iodide ion may be attributed to the halide ligand
exchange of the arylpalladium(II) halide intermediate.3,9
Table 1. Reaction of Ethyl 4-Chlorobenzoate (2a) with Pinacolborane (1a)a
yield (%)b
entry
catalyst
additive
3a
13
84
57
36
5
4a
65
12
30
45
5
1
2
3
4
5
6
7
8
Pd(dba)2/t-Bu-DPEphosc
none
Bu4NI
Bu4NBr
Bu4NCl
none
NiCl2(dppp)d
Bu4NI
Bu4NBr
Bu4NCl
74
85
29
11
7
19

HETEROCYCLES, Vol. 80, No. 1, 2010
215
a Reaction conditions: 2a (0.25 mmol), 1a (0.50 mmol), Et3N (0.75 mmol), catalyst (5
mol%), additive (0.50 mmol), in dioxane at 100 °C. b GC yields are based on 2a. c The
reactions were carried out for 24 h in 1 mL of dioxane by using a catalyst prepared in
d
situ from Pd(dba)2 (12.5 mol) and t-Bu-DPEphos (12.5 mol). The reactions were
carried out for 48 h in 0.25 mL of solvent.
It is known that the borylation of aryl halides was also performed using NiCl2(dppp) as a catalyst;
however, no successful example of the borylation of aryl chlorides 2 has appeared.10 Gratifyingly, this
coupling work was achieved with the aid of tetrabutylammonium halides in analogy with the above
palladium-catalyzed reaction, whereas the absence of tetrabutylammonium halides gave no satisfactory
result as expected (entry 5). Thus, the NiCl2(dppp) catalyst proved to be highly efficient for the borylation
of 2a in the presence of Bu4NBr (entry 7), although replacing the halide anion of tetrabutylammonium
salts gave lower yields under the same conditions (entries 6 and 8).
After optimization of the reaction conditions, we investigated the scope of the borylation of the aryl
chlorides 2 using 1. These results are presented in Table 2. For all the cases listed in Table 2, small
amounts of reduced by-products 4 were produced, but their isolation was very easy. In the first part of this
study, the palladium catalyst system was applied to the coupling of various aryl chlorides 2 with 1a.11 The
present process was extremely tolerant of a variety of common functional groups. Thus, the presence of
functional groups, such as an ester (entries 8 and 9), ketone carbonyl (entries 3 and 4), and cyano groups
(entries 57), in the starting 2 did not interfere with the outcome of the present reaction. In contrast, an
ortho substituent prevented the borylation of 2i, although moderate yield was still obtained (entry 9). The
use of the catalyst derived from Pd(dba)2 and t-Bu-DPEphos demonstrated exceptional level of functional
group toleration, but the NiCl2(dppp) system lacked generality; i.e., several attempts at the selective
nickel-catalyzed borylation of 2 having ketone carbonyl and cyano groups were unsuccessful.
Table 2. Borylation of Representative 2 with 1
yield
(%)b
entry
1
2
conditiona
3
Me
Me
Me
Me
O
O
Cl
CF3
B
B
CF3
1
2c
3
1a
(2b)
A
B
A
84
(3b)
1a 2b
3b
81
Me
Me
Me
O
O
1a
87
COMe
Cl
COMe
Me
(2c)
(3c)

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HETEROCYCLES, Vol. 80, No. 1, 2010
Me
O
Me
Cl
Cl
B
4c
5
1a
1a
1a
1a
1a
1a
A
70
80
88
74
70
57
86
Me
O
Me
COPh
CN
COPh
CN
(2d)
(2e)
(3d)
(3e)
(3f)
(3g)
Me
O
Me
B
B
A
Me
O
Me
Me
O
Me
Cl
6
A
Me
O
CN
Me
(2f)
CN
Me
Me
O
Cl
CN
F
7
A
B
CN
F
Me
O
(2g)
Me
Me
O
Me
Cl
CO2Me
B
B
CO2Me
8
A
Me
O
Me
Me
Me
Me
(2h)
(3h)
F
F
A
O
O
9c
10
Cl
MeO2C
Me
Me
MeO2C
(2i)
(3i)
Me
O
1b 2a
1b 2b
B
B
B
O
CO2Et
(3j)
Me
Me
Me
Me
O
11
77
81
B
CF3
O
(3k)
Me
F
F
Me
O
O
12c
1b
B
B
B
F
Cl
F
(2j)
(3l)
Me
Me
Me
O
13
1b 2h
89
B
CO2Me
O
(3m)
Me
F

HETEROCYCLES, Vol. 80, No. 1, 2010
217
Me
Me
CO2Me
CO2Me
O
14
1b
B
59
Cl
B
O
(2k)
(3n)
F
Me
F
a The reactions were carried out at 100 °C for 24 h by using 2 (0.50 mmol), 1 (1.0
mmol), Et3N (1.5 mmol), Bu4NX (1.0 mmol), and catalyst (25 mol), unless otherwise
noted The catalyst, Bu4NX, and solvent are as follows. Condition A: Pd(dba)2 (25
mol), t-Bu-DPEphos (25 mol), and Bu4NI in dioxane (2 mL). Condition B:
NiCl2(dppp) (25 mol) and Bu4NBr in dioxane (0.5 mL). b Isolated yields are based on
2. c The reactions were conducted for 48 h.
Quite recently, 4,4,6-trimethyl-1,3,2-dioxaborinane (1b) has been used as a borylating reagent to achieve
the palladium-catalyzed borylation of aryl halides; however, this method was limited to aryl iodides and
bromides.12 The second portion of this work involved the application of our protocol to the catalytic
borylation of electron-deficient aryl chlorides 2 with 1b. While the Pd(dba)2/t-Bu-DPEphos/Bu4NI system
was not suitable for the reaction of aryl chlorides with 1b, we were pleased to observe that the
nickel-catalyzed borylation could be carried out in the presence of Bu4NBr. At present, we have no
definitive explanation for the superior efficiency of the nickel catalyst for 1b. Several functionalized aryl
chlorides 2 containing ester group (entries 10, 13, and 14) and fluorine atom (entries 1114) were
efficiently converted to the corresponding products 3.
In conclusion, we have developed a general method for the arylation of cyclic dialkoxyboranes 1 using
electron-deficient aryl chlorides 2 as arylating reagents. The Pd(dba)2/t-Bu-DPEphos or NiCl2(dppp)
catalyst system was effective for the coupling of aryl chlorides, and the selective borylation proceeded by
a treatment with additional tetrabutylammonium halides in either case. Further investigations to broaden
the scope of the organic electrophiles are currently underway in our laboratory.
ACKNOWLEDGEMENTS
This work was partially supported by Grant-in-Aid for Scientific Research on Priority Areas (No.
20036006, "Synergistic Effects for Creation of Functional Molecules") from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. We also thank BASF Corporation for a generous
donation of pinacolborane (1a).
REFERENCES AND NOTES
1. For reviews of the Suzuki coupling, see: (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457;
(b) N. Miyaura, Adv. Organomet. Chem., 1998, 6, 187; (c) N. Miyaura, Top. Curr. Chem., 2002, 219,
11.

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HETEROCYCLES, Vol. 80, No. 1, 2010
2. For reviews of the Miyaura borylation, see: (a) T. Ishiyama and N. Miyaura, J. Organomet. Chem.,
2000, 611, 392; (b) T. Ishiyama and N. Miyaura, Chem. Rec., 2004, 3, 271.
3. (a) M. Murata, S. Watanabe, and Y. Masuda, J. Org. Chem., 1997, 62, 6458; (b) M. Murata, T.
Oyama, S. Watanabe, and Y. Masuda, J. Org. Chem., 2000, 65, 164.
4. O. Baudoin, D. Guénard, and F. Guéritte, J. Org. Chem., 2000, 65, 9268.
5. P. -E. Broutin, I. Čerña, M. Campaniello, F. Leroux, and F. Colobert, Org. Lett., 2004, 6, 4419.
6. M. Murata, T. Sambommatsu, S. Watanabe, and Y. Masuda, Synlett, 2006, 1867.
7. K. L. Billingsley and S. L. Buchwald, J. Org. Chem., 2008, 73, 5589.
8. For a review on palladium-catalyzed couplings of aryl chlorides, see: A. F. Littke and G. C. Fu,
Angew. Chem. Int. Ed., 2002, 41, 4176.
9. (a) M. Murata, M. Ishikura, M. Nagata, S. Watanabe, and Y. Masuda, Org. Lett., 2002, 4, 1843; (b)
M. Murata, H. Ohara, R. Oiwa, S. Watanabe, and Y. Masuda, Synthesis, 2006, 1771; (c) M. Murata,
H. Yamasaki, T. Ueta, M. Nagata, M. Ishikura, S. Watanabe, and Y. Masuda, Tetrahedron, 2007, 63,
4087.
10. (a) A. B. Morgan, J. L. Jurs, and J. M. Tour, J. Appl. Polym. Sci., 2000, 76, 1257; (b) B. M. Rosen, C.
Huang, and V. Percec, Org. Lett., 2008, 10, 2597; (c) D. A. Wilson, C. J. Wilson, B. M. Rosen, and
V. Percec, Org. Lett., 2008, 10, 4879.
11. General Procedure. In a glove box, Pd(dba)2 (25 mol) and t-Bu-DPEphos (25 mol) were placed in
a screw-capped vial containing a stir bar, and dissolved in 2 mL of 1,4-dioxane. After being stirred
for 1 h at room temperature, Et3N (1.5 mmol), Bu4NI (1.0 mmol), aryl chloride 2 (0.50 mmol), and
1a (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 100 °C for 24 h. The resulting mixture was allowed to
cool to room temperature, diluted with Et2O, washed with brine, and dried over Na2SO4. The solvent
was removed under reduced pressure, and the residue was purified by Kugelrohr distillation to give
the desired arylboronate 3.
12. (a) M. Murata, T. Oda, S. Watanabe, and Y. Masuda, Synthesis, 2007, 351; (b) N. Praveen Ganesh
and P. Y. Chavant, Eur. J. Org. Chem., 2008, 4690.