NiCl2(PMe3)2-catalyzed borylation of aryl chlorides

Article abstract of DOI:10.1021/ol202267t

The cross-coupling of aryl chlorides and bis(pinacolato)diboron was achieved using NiCl₂(PMe₃)₂ catalyst in the presence of metal 2,2,2-trifluoroethoxide. The catalyst smoothly provided the desired products regardless of a variety of functional groups and substituted positions.

Full text of DOI:10.1021/ol202267t

ORGANIC
LETTERS
2011
Vol. 13, No. 21
5766–5769
NiCl2(PMe3)2-Catalyzed Borylation of Aryl
Chlorides
Tetsuya Yamamoto, Tomoyuki Morita, Jun Takagi, and Tetsu Yamakawa*
Catalysis Group, Sagami Chemical Research Institute, 2743-1 Hayakawa, Ayase,
Kanagawa 252-1193, Japan
t_yamakawa@sagami.or.jp
Received August 29, 2011
ABSTRACT
The cross-coupling of aryl chlorides and bis(pinacolato)diboron was achieved using NiCl2(PMe3)2 catalyst in the presence of metal 2,2,2-
trifluoroethoxide. The catalyst smoothly provided the desired products regardless of a variety of functional groups and substituted positions.
Arylboronic acids and their derivatives are important
building blocks in organic synthesis.1 In particular, their
application in transition-metal-catalyzed carbonÀcarbon
and carbonÀheteroatom bond formation renders them
one of the most useful synthetic tools in both academic
laboratories and industry.2 The traditional syntheses of
arylboron compounds have technical problems and are
limited in functional group tolerance.1 In the past two
decades, two efficient methods for the synthesis of arylbo-
ronic esters via transition-metal-catalyzed carbonÀboron
bond formation have been developed. One is Rh- or Ir-
catalyzed direct CÀH borylation of arenes,3,4 and the other
is Pd-,5 Ni-,6 or Cu-catalyzed7 substitutional borylation of
aryl halides. Direct CÀH borylation is generally meta- or
para-oriented under typical conditions due to the steric
hindrance of the substituent at the ortho-position. In
contrast, the borylation of substrates with functional
groups such as hydrosilyl4a,b and carbonyl4cÀf occurs only
at the ortho-position of these groups through ortho-meta-
lation. Therefore, direct CÀH borylation is not always
applicable for the synthesis of desired arylboronic esters.
On the other hand, substitutional borylation should
proceed only at the carbonÀhalogen bond and can provide
the desired products from appropriate aryl halides. Pd-
catalyzed borylation was achieved with even aryl chlorides
by the use of electron-rich and bulky5bÀe,g or silica-
supported5m ligands, while Cu-catalyzed borylation was
limited to aryl bromides and iodides.7 The development of
widely available Ni catalysts for substitutional borylation is a
recent topic in the field of cross-coupling reactions. In the past
few years, Percec and Murata independently developed Ni-
catalyzed borylation using dialkoxyborane.6bÀh Although
this borylation proceeds smoothly with aryl halides and
mesylates, it has some limitations with respect to functio-
nalized substrates. Therefore, we have been interested in
the development ofNi-catalyzedborylation withimproved
substrate scope. Herein, we report the NiCl2(PMe3)2-
catalyzed borylation of a wide range of functionalized aryl
chlorides, including sterically challenging substrates using
bis(pinacolato)diboron in the presence of metal 2,2,2-
trifluoroethoxide.
Table 1 shows the results of the Ni-catalyzed borylation
of methyl 4-chlorobenzoate, 1a, using K3PO4 as a base.
(3) For recent reviews, see: (a) Hartwig, J. F. Chem. Soc. Rev. 2011,
40, 1992. (b) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy,
J. M.; Hartwig, J. F. Chem. Rev. 2010, 110, 890.
(1) Boronic Acids; Hall, D. G., Ed.; Wiley-VCH: Weinheim, Germany,
2005.
(2) For selected reviews, see: (a) Liu, C.; Zhang, H.; Shi, W.; Lei, A.
Chem. Rev. 2011, 111, 1780. (b) Partyka, D. V. Chem. Rev. 2011, 111,
1529. (c) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
Resmerita, A. M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346.
(d) Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461.
(e) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275. (f) Corbet,
J.-P.; Mignani, G. Chem. Rev. 2006, 106, 2651.
(4) (a) Robbins, D. W.; Boebel, T. A.; Hartwig, J. F. J. Am. Chem.
Soc. 2010, 132, 4068. (b) Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc.
2008, 130, 7534. (c) Yamazaki, K.; Kawamorita, S.; Ohmiya, H.;
Sawamura, M. Org. Lett. 2010, 12, 3978. (d) Kawamorita, S.; Ohmiya,
H.; Sawamura, M. J. Org. Chem. 2010, 75, 3855. (e) Ishiyama, T.;
Isou, H.; Kikuchi, T.; Miyaura, N. Chem. Commun. 2010, 46, 159.
(f) Miyaura, N. Bull. Chem. Soc. Jpn. 2008, 81, 1535.
r
10.1021/ol202267t
Published on Web 10/06/2011
2011 American Chemical Society

Table 1. Screening of Ni Complexes
Table 2. Effect of the Base on the Ni-Catalyzed Borylation
catalyst
(mol %)
additive
(mol %)
yield of
yield of methyl
benzoatea (%)
additive
(mol %)
yield of
yield of methyl
benzoatea (%)
entry
1
2aa (%)
entry
base
2aa (%)
NiCl2(dppp)
(10)
À
33
5
14
29
0
1
2
3
4
5
6
7
Na3PO4
K2CO3
Cs2CO3
AcOK
À
À
À
À
À
À
16
24
33
0
0
2
2
NiCl2(dppp)
(5)
dppf (10)
6
0
3b
4
NiCl2(dppp)
(5)
dppf (10)
1
PhOK
19
18
0
15
7
t-BuOK
K3PO4
NiCl2(PCy3)2
(10)
À
À
À
À
À
À
À
À
À
13
6
12
64
74
1
H2O
0
(200)
5
NiCl2(PPh3)2
(10)
8
K3PO4
K3PO4
CsF
EtOH
27
88
13
12
3
(200)
6
NiCl2(dmpe)
(10)
12
22
5
9
CF3CH2OH
(200)
7
NiCl2(dppm)
(10)
10
11b
TMSOCH2CF3
(300)
90c
99c
8
NiCl2(dppe)
(10)
6
CsF
TMSOCH2CF3
(210)
0
9
NiCl2(dppf)
(10)
8
40
0
12b
13b
CsF
À
32
0
12
0
À
TMSOCH2CF3
(210)
10
11
12
NiCl2(PMe3)2
(10)
74
73
39
a GC yield based on a calibrated internal standard. b Toluene (1 mL)
was replaced by THF (0.5 mL). c Isolated yield.
NiCl2(PMe3)2
(5)
2
NiCl2(PMe3)2
(1)
6
(entries 10 and 11). Nevertheless, the yield declined to
39% with 1 mol % of NiCl2(PMe3)2.
a GC yield based on a calibrated internal standard. b K3PO4
(1.0 mmol) was replaced by NEt3 (1.5 mmol).
Our next investigation surveyed bases to achieve satis-
factory yields for the borylation with only 1 mol % of
NiCl2(PMe3)2. The results are summarized in Table 2.
Inorganic bases such as Na3PO4, K2CO3, and Cs2CO3,
which have a similar basicity to that of K3PO4, were
not effective for the reaction (entries 1À3). Potassium
acetates5 and alkoxides such as potassium phenoxide8 and
potassium tert-butoxide7a are frequently used for the Pd-
or Cu-catalyzed borylation of aryl halides and triflates.
NiCl2(dppp)/NEt3 is known as an efficient catalyst for the
borylation of aryl halides using dialkoxyboranes.6bÀi
Moreover, NiCl2(PCy3)2/inorganic base catalyzes the bor-
ylation of aryl carbamates using bis(neopentylglycolato)-
diboron.6a However, these Ni catalyst systems were not
effective for this borylation (entries 1À4). Conventional
Ni-phosphine complexes such as NiCl2(dmpe), NiCl2-
(PPh3)2, NiCl2(dppm), NiCl2(dppe), and NiCl2(dppf)
also exhibited poor activity (entries 5À9). In contrast,
NiCl2(PMe3)2 catalyzed the borylation in good yield
(6) (a) Huang, K.; Yu, D.-G.; Zheng, S.-F.; Wu, Z.-H.; Shi, Z.-J.
Chem.;Eur. J. 2011, 17, 786. (b) Murata, M.; Sambommatsu, T.;
Oda, T.; Watanabe, S.; Masuda, Y. Heterocycles 2010, 80, 213.
(c) Leowanawat, P.; Resmerita, A.-M.; Moldoveanu, C.; Liu, C.; Zhang,
N.; Wilson, D. A.; Hoang, L. M.; Rosen, B. M.; Percec, V.
J. Org. Chem. 2010, 75, 7822. (d) Moldoveanu, C.; Wilson, D. A.; Wilson,
C. J.; Leowanawat, P.; Resmerita, A.-M.; Liu, C.; Rosen, B. M.; Percec,
V. J. Org. Chem. 2010, 75, 5438. (e) Wilson, D. A.; Wilson, C. J.;
Moldoveanu, C.; Resmerita, A.-M.; Corcoran, P.; Hoang, L. M.; Rosen,
B. M.; Percec, V. J. Am. Chem. Soc. 2010, 132, 1800. (f) Moldoveanu, C.;
Wilson, D. A.; Wilson, C. J.; Corcoran, P.; Rosen, B. M.; Percec, V. Org.
Lett. 2009, 11, 4974. (g) Wilson, D. A.; Wilson, C. J.; Rosen, B. M.;Percec,
V. Org. Lett. 2008, 10, 4879. (h) Rosen, B. M.; Huang, C.; Percec, V. Org.
Lett. 2008, 10, 2597. (i) Morgan, A. B.; Jurs, J. L.; Tour, J. M. J. Appl.
Polym. Sci. 2000, 76, 1257.
(7) (a) Kleeberg, C.; Dang, L.; Lin, Z. Y.; Marder, T. B. Angew.
Chem., Int. Ed. 2009, 48, 5350. (b) Zhu, W.; Ma, D. Org. Lett. 2006, 8,
261. (c) Fang, H.; Kaur, G.; Yan, J.; Wang, B. Tetrahedron Lett. 2005,
46, 671.
(8) Takagi, J.; Takahashi, K.; Ishiyama, T.; Miyaura, N. J. Am.
Chem. Soc. 2002, 124, 8001.
(5) (a) Tang, M.; Keshipeddy, S.; Zhang, Y.; Wei, X.; Savoie, J.;
Patel, N. D.; Yee, N. K.; Senanayake, C. H. Org. Lett. 2011, 13, 1366.
(b) Molander, G. A.; Trice, S. L. J.; Dreher, S. D. J. Am. Chem. Soc.
2010, 132, 17701. (c) Billingsley, K. L.; Buchwald, S. L. J. Org. Chem.
2008, 73, 5589. (d) Billingsley, K. L.; Barder, T. E.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2007, 46, 5359. (e) Murata, M.; Sambommatsu,
T.; Watanabe, S.; Masuda, Y. Synlett 2006, 1867. (f) Broutin, P. E.;
Cerna, I.; Campaniello, M.; Leroux, F.; Colobert, F. Org. Lett. 2004, 6,
4419. (g) Ishiyama, T.; Ishida, K.; Miyaura, N. Tetrahedron 2001, 57,
9813. (h) Baudoin, O.; Guenard, D.; Gueritte, F. J. Org. Chem. 2000, 65,
9268. (i) Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. J. Org.
Chem. 2000, 65, 164. (j) Murata, M.; Watanabe, S.; Masuda, Y. J. Org.
Chem. 1997, 62, 6458. (k) Ishiyama, T.; Itoh, Y.; Kitano, T.; Miyaura, N.
Tetrahedron Lett. 1997, 38, 3447. (l) Ishiyama, T.; Murata, M.; Miyaura,
N. J. Org. Chem. 1995, 60, 7508. (m) Kawamorita, S.; Ohmiya, H.; Iwai,
T.; Sawamura, M. Angew. Chem., Int. Ed. 2011, 50, 8363.
Org. Lett., Vol. 13, No. 21, 2011
5767

Table 3. Borylation of Para- and Meta-Substituted Aryl
Chlorides
Table 4. Borylation of Ortho-Substituted Aryl Halides
a Isolated yield. b THF was replaced by toluene. c THF was replaced
by 1,4-dioxane. d Reaction temperature was 120 °C. e The reaction was
carried out with bis(pinacolato)diboron (1.0 mmol, 2.0 equiv), CsF (1.5
mmol, 3.0 equiv), and TMSCH2CF3 (1.75 mmol, 3.5 equiv) at 135 °C.
a Isolated yield. b THF was replaced by 1,4-dioxane.
Then, we examined the addition of various metal 2,2,2-
trifluoroethoxides on the reaction. Since metal 2,2,2-tri-
fluoroethoxidesareknowntobeexplosive,10 weperformed
the reactions using a mixture of an inorganic salt and
However, these bases afforded a low yield for the present
borylation (entries 4À6). We then attempted the addition
of protic compounds, which are known to accelerate
transition-metal-catalyzed borylation with diborons.9
However, the addition of H2O and ethanol in the boryla-
tion using K3PO4 afforded lower yields (entries 7 and 8). In
contrast, 2,2,2-trifluoroethanol drastically improved the
yield (entry 9), suggesting that potassium 2,2,2-trifluoro-
ethoxide generated in situ worked effectively as a base.
(9) For selected papers, see: (a) Thorpe, S. B.; Guo, X.; Santos, W. L.
Chem. Commun. 2011, 47, 424. (b) Tobisu, M.; Fujihara, H.; Koh, K.;
Chatani, N. J. Org. Chem. 2010, 75, 4841. (c) Hirano, K.; Yorimitsu, H.;
Oshima, K. Org. Lett. 2007, 9, 5031. (d) Mun, S.; Lee, J. E.; Yun, J. Org.
Lett. 2006, 8, 4887.
5768
Org. Lett., Vol. 13, No. 21, 2011

trimethyl(2,2,2-trifluoroethoxy)silane. As a result, the yield
reached 90% using CsF (entry 10). The use of THF instead
of toluene further improved the yield to 99% (entry 11).
Since the addition of only CsF or TMSOCH2CF3 afforded
a pooryield, it canbe concluded thatcesium 2,2,2-trifluoro-
ethoxide is required to obtain an excellent yield (entry 11
vs 12 and 13).
The scope of various aryl halides in this borylation is
summarized in Tables 3 and 4. Table 3 shows the results
using para- and meta-substituted aryl chlorides. The reac-
tions proceeded smoothly with substrates having various
functional groups, which included carbonyl, amide, un-
protected amine, protected boryl,12 and alkenyl groups
(entries 1À4, 6, 8, and 10). For the borylation of amide-
substituted aryl chlorides, 1,4-dioxane was a better solvent
than THF in terms of yield (entries 3 and 4). The chloro
moietyonthe alkyl substituentremainedintactunder these
reaction conditions (entry 9). Aryl chlorides with electron-
withdrawing substituents such as 1b, 1c, and 1d gave
satisfactory yields with 1À2 mol % of catalyst (entries
1À3). In contrast, more catalyst (3À5 mol %) was required
to obtain good yields in the borylation of electron-rich aryl
chlorides, 1f, 1g, 1j, and 1l (entries 5, 6, 9, and 11).
aniline in satisfactory yields (entries 1 and 2), indicat-
ing that this catalyst system is exceptionally suitable for
ortho-substituted substrates. Additionally, bromo deriva-
tives were borylated for a much shorter reaction time than
chloroderivatives (entries 3 and 4). Satisfactory yieldswere
obtained even when the substrates featured sterically bulky
substituents such as 1s and 1t, although higher reaction
temperatures and 5À10 mol % of catalyst were required
(entries 9 and 10). It is known that the borylation of 2,6-
substituted aryl halides is difficult due to steric hindrance
and has only been achieved using a Pd catalyst for aryl
chlorides.5a,d,m So far, no report on the Ni-catalyzed
borylation of 2,6-substituted aryl chlorides has been pub-
lished. Therefore, it is noteworthy that the result shown in
entry 9 is the first example of Ni-catalyzed borylation of a
2,6-substituted aryl chloride.
In conclusion, we demonstrated that the combination of
NiCl2(PMe3)2, CsF, and TMSOCH2CF3 is an efficient
catalyst system for the borylation of various aryl halides
with bis(pinacolato)diboron. In particular, metal 2,2,2-
trifluoroethoxides are rare bases for the coupling reaction.
Further work is underway to expand the scope of substrates
and clarify the effect of the metal fluorinated alkoxides.
Table 4 summarizes the results of the borylation of
ortho-substituted aryl halides. Interestingly, the catalyst
system of NiCl2(PMe3)2, CsF, and TMSOCH2CF3 was
revealed to borylate ethyl 2-chlorobenzoates and 2-chloro
Acknowledgment. We thank the Instrumental Analysis
Laboratory, University of Toyama for the HRMS mea-
surements. The authors are also grateful to the Tosoh
F-Tech Inc. for the generous gift of 2,2,2-trifluoroethanol
and to Tosoh corporation for the gift of 1-chloro-4-(4-
chlorobutoxy)benzene.
(10) Schmutz, J. L.; Allock, H. R. Inorg. Chem. 1975, 14, 2433.
(11) (a) Lee, B.; Kim, J.-H.; Lee, H.; Ahn, B.-S.; Cheong, M.; Kim,
H.-S.; Kim, H. J. Fluorine Chem. 2007, 128, 110. (b) Hagen, H.;
Kirchmeier, R. L.; Shreeve, J. M. Inorg. Chem. 1994, 33, 6369.
(12) (a) Iwadate, N.; Suginome, M. Chem. Lett. 2010, 39, 558.
(b) Iwadate, N.; Suginome, M. J. Am. Chem. Soc. 2010, 132, 2548.
(c) Iwadate, N.; Suginome, M. Org. Lett. 2009, 11, 1899. (d) Iwadate, N.;
Suginome, M. J. Organomet. Chem. 2009, 694, 1713. (e) Noguchi, H.;
Shioda, T.; Chou, C.-M.; Suginome, M. Org. Lett. 2008,10,377.(f)Noguchi,
H.; Hojo, K.; Suginome, M. J. Am. Chem. Soc. 2007, 129, 758.
Supporting Information Available. Experimental pro-
cedures and spectral data for isolated products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Org. Lett., Vol. 13, No. 21, 2011
5769