Functionalizations of aryl C-H bonds in 2-arylpyridines via sequential borylation and copper catalysis

Article abstract of DOI:10.1002/adsc.201100930

Selective functionalizations of aryl C-H bonds in 2-arylpyridines have been developed via sequential borylation and aerobic oxidative copper catalysis, and the corresponding aryl halides, sulfones, azides and arylamines were obtained in good yields. The protocol uses cheap and readily available boron tribromide (BBr₃) as the borylating reagent, and inorganic salts (potassium iodide, ammonium bromide, sodium alkylsulfinates, sodium azide) as the functional group sources. This method makes functionalizations of aryl C-H bonds easy. Copyright

Full text of DOI:10.1002/adsc.201100930

FULL PAPERS
DOI: 10.1002/adsc.201100930
À
Functionalizations of Aryl C H Bonds in 2-Arylpyridines via
Sequential Borylation and Copper Catalysis
Liting Niu,a Haijun Yang,a Daoshan Yang,a and Hua Fua,*
a
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084, Peopleꢀs Republic of China
Fax : (+86)-10-6278-1695; e-mail: fuhua@mail.tsinghua.edu.cn
Received: November 29, 2011; Revised: March 18, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201100930.
À
Abstract: Selective functionalizations of aryl C H organic salts (potassium iodide, ammonium bromide,
bonds in 2-arylpyridines have been developed via se- sodium alkylsulfinates, sodium azide) as the func-
quential borylation and aerobic oxidative copper cat- tional group sources. This method makes functionali-
À
alysis, and the corresponding aryl halides, sulfones, zations of aryl C H bonds easy.
azides and arylamines were obtained in good yields.
À
The protocol uses cheap and readily available boron Keywords: aerobic oxidation; borylation; C H func-
tribromide (BBr3) as the borylating reagent, and in- tionalization; copper; functional groups
Introduction
proaches avoiding haloarenes include [4+2]cycload-
ditions,[14] aryl-CH deprotonation,[15] diazonium
Aromatic compounds containing functional groups ions,[16] and arene borylation with boronium cations.[17]
À
such as halides, sulfones, azides and amines are essen- Recently, the selective C H bond functionalization
tial substances,[1] and they are widely used in chemi- has attracted much attention.[18] Iridium-catalyzed
À
cals, synthetic intermediates, pharmaceuticals, natural arene C H bond borylation has also been devel-
products, and materials. Therefore, it is of importance oped.[19] Very recently, Murakami and co-workers re-
to develop highly efficient and economical ap- ported a simple and practical transition metal-free
proaches to these aromatic compounds. Although synthesis of 2-arylpyridine-dibromoborane complexes
there has been great progress in palladium- or through treatment of substituted 2-arylpyridines with
copper-catalyzed synthesis of aryl halides,[2] sulfones,[3] BBr3 at room temperature.[20] Encouraged by the re-
azides,[4] and arylamines,[5] some drawbacks restrict sults, herein, we report selective functionalizations of
À
their wide application, such as the use of expensive, aryl C H bonds in 2-arylpyridines via sequential bor-
toxic catalysts and ligands for palladium catalysis; ylation and copper catalysis.
harsh reaction conditions and limited substrate scope
In the previous reports, the pyridine moiety of 2-ar-
for copper catalysis. Arylboronic acids and their ylpyridines was used as the directing group in the
esters are common synthetic building blocks,[6] and functionalizations of C H bonds. However, some ex-
À
they have been used in the synthesis of aryl halides,[7] pensive transition metals such as Pd, Ru, Rh, Pt, Ir,
aryl sulfones,[8] aryl azides,[9] arylamines[10] under mild special oxidants, and higher reaction temperature
conditions via the Chan–Lam–Evans coupling strat- were required, and a catalyst system could run only
egy.[11] Recently, we have developed general copper- for one kind of special reaction.[18g,q,u,19a] To the best of
catalyzed transformations of functional groups on aro- our knowledge, there is no a general method for the
matic rings from arylboronic acids in water at room assembly of functional groups on aromatic rings via
temperature.[12] Therefore, it is very favorable to de- C H activity thus far. Here, a novel and general path-
À
velop an easy preparation of aryl boron compounds way is disclosed as shown in Scheme 1. This proce-
and an efficient functionalization of arenes. In the dure involves sequential two-step reactions: metal-
À
previous methods, arylboronate esters are commonly free pyridine-directing C H borylation (developed by
synthesized from haloarenes and either stoichiometric Murakami et al.) and copper-catalyzed aerobic oxida-
hard organometallic reagents or transition metal-cata- tive coupling.
lyzed cross-couplings.[6,13] Some alternative ap-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
ÞÞ
These are not the final page numbers!

Liting Niu et al.
FULL PAPERS
in organic synthesis. At first, 2-phenylpyridine was
used as the model substrate to optimize the iodination
conditions. Reaction of 2-phenylpyridine (1a) with
3 equivalents of BBr3 in the presence of (i-Pr)2NEt
(one equivalent) in dry CH2Cl2 at 08C to room tem-
perature provided the crude 2-phenylpyridine-dibro-
moborane complex (2a),[20] and this was applied in an
optimization of conditions for the copper-catalyzed
iodination with NaI including catalysts, additives/li-
gands, solvents and temperature as shown in Table 1.
Various copper-ammonia catalyst systems (0.1 equiv.
relative to the amount of 1a) were screened in etha-
nol using 5 equiv. of NaI as the partner of 2a (prepa-
ration of copper-ammonia catalyst systems: a mixture
of 0.1 equiv. of copper salt and 2.5 equiv. of aqueous
ammonia was stirred for 30 min under air) (entries 1–
5), and the Cu2O/NH3 catalyst system showed the
highest catalytic activity (entry 3). It is worthwhile to
À
Scheme 1. Our strategy on functionalizations of aryl C H
bonds. Reaction conditions: i) C H bond borylation with
À
BBr3; ii) copper-catalyzed introduction of functional groups
under air.
Results and Discussion
Aryl halides are important chemical intermediates note that no 2-(pyridin-2-yl)benzenamine was ob-
and materials, they are widely used in various fields, served, and the result is attributed to the higher nu-
so selective halogenation of arenes is a key direction cleophilic power of the IÀ ion than of ammonia (here,
Table 1. Copper-catalyzed iodination of 2-phenylpyridine to 2-(2-iodophenyl)pyridine via borylation with BBr3 and copper
catalysis: optimization of reaction conditions.[a]
Entry
Catalyst
Additive [mmol]
Solvent
Temperature [8C]
Yield [%][b]
1
2
3
4
5
6
7
8
CuBr
CuI
Cu2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
NH3·H2O
K2CO3
EtOH
EtOH
EtOH
EtOH
EtOH
CHCl3
CH3CN
i-PrOH
H2O
45
45
45
45
45
45
45
45
45
45
45
45
45
45
25
40
60
45
45
45
40
35
80
38
27
trace
36
20
10
15
trace
15
18
trace
0
Cu
N
CuSO4
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
–
9
10
11
12
13
14
15
16
17
18
19
20
THF
MeOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
K3PO4
pyridine
NH3·H2O
NH3·H2O
NH3·H2O
–
50
15
trace[c]
trace[d]
trace[e]
NH3·H2O
NH3·H2O
Cu2O
[a]
Reaction conditions: 2-phenylpyridine (1 mmol), catalyst (0.1 mmol), additive (2.5 mmol), NaI (5 mmol), solvent (3 mL)
under air. Reaction time: 10 h.
Isolated yield.
No addition of NH3·H2O.
No addition of copper catalyst.
Under a nitrogen atmosphere.
[b]
[c]
[d]
[e]
2
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

À
Functionalizations of Aryl C H Bonds in 2-Arylpyridines via Sequential Borylation
Table 2. Copper-catalyzed synthesis of aryl iodides, bromide, sulfones, azides and amines.[a]
[a]
Reaction conditions: 1 (1 mmol), BBr3 (3 mmol), (i-Pr)2NEt (1 mmol) CH2Cl2 (0.5 mL), NaI
(5 mmol), NH3·H2O (5 mmol) (extra NH3·H2O was required for the synthesis of aryl bro-
mides), NaSO2R (5 mmol), NaN3 (5 mmol), Cu2O (0.1 mmol), NH3·H2O (2.5 mmol) (as
ligand or additive of copper catalyst), C2H5OH (3 mL) under air, reaction temperature:
458C. Isolated yield from 1 to the target product 2.
ammonia could act as the additive/ligand of the cated that the iodination involved an aerobic oxida-
copper catalyst). The effect of solvents was investigat- tive process. Therefore, the optimal reaction condi-
ed (compare entries 3, 6–11), and ethanol gave the tions for the iodination 2-arylpyridine-dibromoborane
best result (entry 3). Several additives were used (en- complexes are as follows: 0.1 equiv. of Cu2O/NH3
tries 12–14) but they showed poor results. Various re- complex as the catalyst system, ethanol as the solvent,
action temperatures were attempted (compare en- 5 equiv. of NaI as the iodic source, and the reaction
tries 3, 15–17), and 458C was suitable. Only a trace was carried out under air at 458C.
amount of product was observed in the absence of ad-
We investigated the scope of this copper-catalyzed
ditive/ligand or copper catalyst (see entries 18 and iodination of substituted 2-arylpyridines. As shown in
19). Only a trace amount of product was found under Table 2, A, the examined substrates provided good to
a nitrogen atmosphere (entry 20), and the result indi- excellent yields, and the substrates containing elec-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3
ÞÞ
These are not the final page numbers!

Liting Niu et al.
FULL PAPERS
Scheme 2. A) Reaction of 2-p-tolylpyridine-dibromoborane
complex (2b) with ethanol; B) treatment of 2b with 25%
aqueous ammonia in ethanol.
Scheme 3. Bromination of 2-arylpyridine-dibromoborane
complexes under air.
tron-withdrawing groups exhibited higher reactivity transformation of 2-(2-azidophenyl)pyridine (6a) in
than ones containing electron-donating groups. In 4 h under the standard conditions, and 2-(pyridin-2-
order to explore the copper-catalyzed chemistry of 2- yl)benzenamine (7a) was obtained in 80% yield. Re-
arylpyridine-dibromoborane complexes under our action of 2-phenylpyridine-dibromoborane complex
standard condition, we performed the following con- (2a) with NaN3 in phenylmethanol (as the solvent)
1
trol experiments as monitored by in situ H NMR. As was performed under copper-catalyzed aerobic oxida-
1
shown in Scheme 2, reaction of 2-p-tolylpyridine-di- tive condition (Scheme 4, B), and in situ H, 13C NMR
bromoborane complex (2b) with ethanol provided the spectra of the resulting solution showed the peaks at
boronate ester (2’), and treatment of 2b with 25% 9.94 and 192.3 ppm, which indicated the formation of
aqueous ammonia in ethanol gave the corresponding an aldehyde group. In addition, product 7a was ob-
boronic acid (2’’). Therefore, the iodination of substi- tained in 45% yield. The results showed that aryl
tuted 2-arylpyridines can proceed from copper-cata- azides could be transformed into arylamines under
lyzed reactions of arylboronic acids with NaI in the our copper-catalyzed condition. A possible mecha-
reaction system. It is worthwhile to note that no aryl nism for transformation of aryl azides to arylamines is
bromide was observed, and the result was also attrib- proposed in Scheme 4, C. Coordination of 6 with
uted to higher nucleophilic power of IÀ ion than BrÀ Cu(I) and ethanol forms intermediate II, and reduc-
ion and more IÀ ion (5 equiv. for IÀ ion, 2 equiv. for tion of 6 by ethanol provides the corresponding aryla-
BrÀ ion).
mine releasing acetaldehyde and copper catalyst. The
Furthermore, we explored the copper-catalyzed similar copper-catalyzed oxidation of alcohols to alde-
bromination of substituted 2-arylpyridines as shown hydes was previously investigated by us and other
in Table 2, B. Here, an extra 5 equiv. of NH3·H2O was groups.[21]
À
added to the reaction system to promote hydrolysis of
The functionalizations of C H bonds in Table 2
À
the 2-arylpyridine-dibromoborane complex freeing 2- could tolerate some functional groups including C Cl
(pyridin-2-yl)phenylboronic acid (I) and BrÀ ion, and bond, C Br bond, hydroxy group, N-hetercyclic ring
À
then copper-catalyzed aerobic oxidative coupling of I in the substrates.
with BrÀ provided the corresponding aryl bromides
(4) (see Scheme 3). Therefore, no additional bromine
source was required in this reaction.
Conclusions
Inspired by the excellent results mentioned above,
we used the same copper catalyst system (Cu2O/NH3) We have developed an efficient, copper-catalyzed
À
to make aryl sulfones with NaSO2Me and method for C H functionalizations of substituted 2-
NaSO2PhMe as the sulfone sources (See Table 2, C). arylpyridines to lead to the corresponding aryl io-
Fortunately, the copper catalyst system worked well dides, bromides, sulfones, azides and amines, and the
for the sufonization of substituted 2-arylpyridines procedure comprises sequential borylation and
through borylation and copper-catalyzed aerobic oxi- copper-catalyzed aerobic oxidative couplings. The
dative couplings.
borylation was easily performed with BBr3 in the
Reactions of 2-arylpyridine-dibromoborane com- presence of (i-Pr)2NEt. The protocol of copper-cata-
plexes with NaN3 were also investigated under the lyzed aerobic oxidative couplings uses very cheap
standard condition (see Table 2, D and E). Interest- Cu2O/NH3 as the catalyst system, oxygen in air as the
ingly, aryl azides were formed in a short time (0.75– oxidant, ethanol as the solvent, and the readily avail-
2 h), but arylamines required a longer reaction time able and cheap reagents (NaI, NH4Br, NaSO2R and
(>3 h). As shown in Scheme 4, A, we attempted the NaN3) as the sources of the functional groups, and the
4
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

À
Functionalizations of Aryl C H Bonds in 2-Arylpyridines via Sequential Borylation
Scheme 4. A) Transformation of 2-(2-azidophenyl)pyridine (6a) to form 2-2-(pyridin-2-yl)benzenamine (7a); B) possible
mechanism for the transformation of aryl azides to arylamines.
functionalizations worked well under mild conditions.
The method can tolerate some functional groups in
the substrates. This convenient and efficient approach
should attract much attention in academic and indus-
trial fields.
ganic phase was dried over anhydrous Na2SO4, filtered, and
concentrated, and the residue was purified by column chro-
matography on silica gel or by thin layer chromatography to
give the desired product (3–7).
A further preparative silica gel TLC isolation was re-
quired for the impure product. Five representative examples
are shown as follows:
2-(2-Iodo-4-methylphenyl)pyridine (3b): Eluent: petrole-
um ether/ethyl acetate=20:1; yield: 100.2 mg (84%); yellow
oil. 1H NMR (CDCl3, 300 MHz): d=8.68 (d, 1H, J=
4.8 Hz), 7.79 (s, 1H), 7.74 (t, 1H, J=7.2 Hz), 7.47 (d, 1H,
J=7.6 Hz), 7.33 (d, 1H, J=7.6 Hz), 7.24 (m, 2H), 2.34 (s,
3H); 13C NMR (CDCl3, 75 MHz): d=160.7, 149.3, 142.3,
140.3, 139.9, 136.0, 130.1, 129.2, 124.6, 122.4, 96.6, 20.7; EI-
MS: m/z=295.8 [M]+.
2-(2-Bromo-4-chlorophenyl)pyridine (4c): Eluent: petrole-
um ether/ethyl acetate=20:1; yield: 92.1 mg (69%); red oil.
1H NMR (CDCl3, 300 MHz): d=8.70 (d, 1H, J=4.8 Hz),
7.76 (t, 1H, J=7.6 Hz), 7.69 (s, 1H), 7.59 (d, 1H, J=
7.6 Hz), 7.49 (d, 1H, J=8.3 Hz), 7.39 (d, 1H, J=8.3 Hz),
7.30 (t, 1H, J=6.9 Hz); 13C NMR (CDCl3, 75 MHz): d=
157.3, 149.6, 138.9, 136.0, 134.9, 133.0, 132.3, 127.9, 124.8,
122.8, 122.2; EI-MS: m/z=268.0 [M]+.
Experimental Section
General Procedure for Functionizations of
Substituted 2-Phenypyridines Leading to 3–7
1.5 mmol of BBr3 in dry CH2Cl2 (1.5 mL) were added drop-
wise to a solution of substituted 2-arylpyridine (0.5 mmol),
(i-Pr)2NEt (0.5 mmol, 65 mg) in 0.5 mL of CH2Cl2 at 08C,
and then the mixture was stirred for 24 h at room tempera-
ture. Saturated aqueous K2CO3 solution (5 mL) was added
to the resulting mixture, the organic phase was isolated, and
the aqueous layer was extracted with CH2Cl2 (3ꢂ3 mL).
The combined organic phase was dried over anhydrous
MgSO4, filtered, and concentrated to get the crude product,
the substituted 2-arylpyridine dibromoborane complex (2)
(The procedure was performed according to Murakami and
co-workersꢀ report[20]).
Cu2O (0.1 mmol, 14.3 mg) and 25% aqueous ammonia
(0.19 mL, 2.5 mmol of NH3) were added to a round-bottom
flask charged with a stirrer, and the mixture was was stirred
for 30 min under air at room temperature (~258C). Then, 2,
ethanol (3 mL) and the other reagent [NaI, NH3·H2O,
NaSO2R or NaN3 (5 mmol)] was added to the flask, and the
solution was stirred under air at 458C until the reaction was
completed (as determined by TLC). The solvent in the re-
sulting solution was removed on a rotary evaporator, water
(5 mL) was added to the residue, and the target product was
extracted with ethyl acetate (3ꢂ3 mL). The combined or-
2-(Pyridin-2-yl) phenylmethanesulfinate (5a): Eluent: pe-
troleum ether/ethyl acetate=2:1; yield: 102.9 mg (88%);
1
colorless solid; mp 138–1398C. H NMR (CDCl3, 300 MHz):
d=8.61 (s, 1H), 8.19 (t, 1H, J=6.2 Hz), 7.76 (m, 1H), 7.65
(m, 2H), 7.45 (d, 2H, J=6.2 Hz), 7.32 (d, 1H, J=6.2 Hz),
3.31 (s, 3H); 13C NMR (CDCl3, 75 MHz): d=158.0, 148.5,
141.2, 139.2, 136.8, 133.5, 131.8, 130.0, 128.9, 124.6, 123.0,
46.3; EI-MS: m/z=234.9 [M]+.
2-(2-Azido-4-methylphenyl)pyridine (6b): Eluent: petrole-
um ether/ethyl acetate=20:1; yield. 73.5 mg (70%); yellow
oil. 1H NMR (DMSO-d6, 600 MHz): d=8.68 (d, 1H, J=
4.8 Hz), 7.83 (t, 1H, J=7.9 Hz), 7.75 (d, 1H, J=8.1 Hz),
7.57 (d, 1H, J=8.2 Hz), 7.25 (m, 1H), 7.21 (s, 1H), 7.11 (d,
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

Liting Niu et al.
FULL PAPERS
1H, J=8.2 Hz), 2.39 (s, 3H); 13C NMR (DMSO-d6,
150 MHz): d=155.4, 149.9, 140.6, 136.9, 136.6, 131.6, 129.6,
126.5, 125.1, 122.8, 120.2, 21.5; EI-MS: m/z=211.1 [M]+.
5-Chloro-2-(pyridin-2-yl)benzenamine (7c): Eluent: petro-
leum ether/ethyl acetate=10:1; yield: 65.3 mg (64%); white
Wu, J. Hynes Jr, Org. Lett. 2010, 12, 1192; j) J. M.
Murphy, X. Liao, J. F. Hartwig, J. Am. Chem. Soc. 2007,
129, 15434.
[8] For the synthesis of aryl sulfones, see: a) A. Kar, I. A.
Sayyed, W. F. Lo, H. M. Kaiser, M. Beller, M. K. Tse,
Org. Lett. 2007, 9, 3405; b) F. Huang, R. A. Batey, Tet-
rahedron 2007, 63, 7667; c) B. P. Bandgar, S. V. Betti-
geri, J. Phopase, Org. Lett. 2004, 6, 2105.
[9] For the synthesis of aryl azides, see: a) Y. Li, L.-X.
Gao, F.-S. Han, Chem. Eur. J. 2010, 16, 7969; b) C. Tao,
X. Cui, J. Li, A. Liu, L. Liu, Q. Guo, Tetrahedron Lett.
2007, 48, 3525; c) H. Zheng, R. McDonald, D. G. Hall,
Chem. Eur. J. 2010, 16, 5454.
1
solid; mp 178–1798C. H NMR (DMSO-d6, 600 MHz): d=
8.60 (d, 1H, J=4.1 Hz), 7.87 (t, 1H, J=7.6 Hz), 7.79 (d, 1H,
J=8.3 Hz), 7.57 (d, 1H, J=8.3 Hz), 7.30 (t, 1H, J=4.8 Hz),
6.91 (s, 2H), 6.84 (s, 1H), 6.61 (d, 1H, J=6.2 Hz); 13C NMR
(DMSO-d6, 150 MHz): d=158.3, 149.6, 148.2, 137.8, 134.5,
131.2, 122.2, 121.8, 119.3, 115.8, 115.7; EI-MS: m/z=205.1
[M]+.
[10] For the synthesis of arylamines, see: a) H. Rao, H. Fu,
Y. Jiang, Y. Zhao, Angew. Chem. 2009, 121, 1134;
Angew. Chem. Int. Ed. 2009, 48, 1114; b) Z. Jiang, Z.
Wu, L. Wang, D. Wu, X. Zhou, Can. J. Chem. 2010, 88,
964.
[11] Selected references, see: a) P. Y. S. Lam, C. G. Clark, S.
Saubern, J. Adams, M. P. Winters, D. M. T. Chan, A.
Combs, Tetrahedron Lett. 1998, 39, 2941; b) D. A.
Evans, J. L. Katz, T. R. West, Tetrahedron Lett. 1998,
39, 2937; c) A. P. Combs, S. Saubern, M. Rafalski,
P. Y. S. Lam, Tetrahedron Lett. 1999, 40, 1623; d) P. Y. S.
Lam, C. G. Clark, S. Saubern, J. Adams, K. M. Averill,
D. M. T. Chan, A. Combs, Synlett 2000, 674.
Acknowledgements
The authors wish to thank the National Natural Science
Foundation of China (Grant Nos. 20972083, 21172128 and
21105054) and the Ministry of Science and Technology of
China (2012CB722600) for financial support.
References
[1] a) Science of Synthesis, Volume 31, (Ed.: C. A. Rams-
den), Thieme, Stuttgart, Germany, 2007; b) Chiral
Amine Synthesis, (Ed.: T. C. Nugent), Wiley-VCH,
Weinheim, Germany, 2010.
[12] H. Yang, Y. Li, M. Jiang, J. Wang, H. Fu, Chem. Eur. J.
2011, 17, 5652.
[13] a) T. Ishiyama, M. Murata, N. Miyaura, J. Org. Chem.
1995, 60, 7508; b) M. Murata, T. Oyama, S. Watanabe,
Y. Masuda, J. Org. Chem. 2000, 65, 164; c) T. Ishiyama,
N. Miyaura, Chem. Rec. 2004, 3, 271; d) C. Kleeberg, L.
Dang, Z. Lin, T. B. Marder, Angew. Chem. 2009, 121,
5454; Angew. Chem. Int. Ed. 2009, 48, 5350; e) S. Clau-
del, C. Gosmini, J.-M. Paris, J. Perichon, Chem.
Commun. 2007, 3667; f) C. Moldoveanu, D. A. Wilson,
C. J. Wilson, P. Leowanawat, A.-M. Resemerita, C. Liu,
B. M. Rosen, V. Percec, J. Org. Chem. 2010, 75, 5438.
[14] A.-L. Auvinet, J. P. A. Harrity, G. Hilt, J. Org. Chem.
2010, 75, 3893.
[15] a) V. Snieckus, Chem. Rev. 1990, 90, 879; b) E. Tyrrell,
P. Brookes, Synthesis 2004, 469.
[16] F. Mo, Y. Jiang, D. Qiu, Y. Zhang, J. Wang, Angew.
Chem. 2010, 122, 1890; Angew. Chem. Int. Ed. 2010, 49,
1846.
[2] a) A. Klapars, S. L. Buchwald, J. Am. Chem. Soc. 2002,
124, 14844; b) K. A. Cannon, M. E. Geuther, C. K.
Kelly, S. Lin, A. H. R. MacArthur, Organometallics
2011, 30, 4067; c) T. Furuya, A. S. Kamlet, T. Ritter,
Nature 2011, 473, 470.
[3] a) S. Cacchi, G. Fabrizi, A. Goggiamani, L. M. Parisi,
R. Bernini, J. Org. Chem. 2004, 69, 5608; b) W. Zhu, D.
Ma, J. Org. Chem. 2005, 70, 2696.
[4] a) W. Zhu, D. Ma, Chem. Commun. 2004, 888; b) J. An-
dersen, U. Madsen, F. Bjorkling, X. Liang, Synlett 2005,
2209.
[5] a) Q. Shen, J. F. Hartwig, J. Am. Chem. Soc. 2006, 128,
10028; b) N. Xia, M. Taillefer, Angew. Chem. 2009, 121,
343; Angew. Chem. Int. Ed. 2009, 48, 337; c) H. Xu, C.
Wolf, Chem. Commun. 2009, 3035; d) J. Kim, S. Chang,
Chem. Commun. 2008, 3052; e) R. Ntaganda, B. Dhud-
shia, C. L. B. Macdonaldz, A. N. Thadani, Chem.
Commun. 2008, 6200.
[17] A. Del Grosso, P.lJ. Singleton, C. A. Muryn, M. J. In-
gleson, Angew. Chem. 2011, 123, 2150; Angew. Chem.
Int. Ed. 2011, 50, 2102.
[6] D. G. Hall, Boronic Acids: Preparation, Applications in
Organic Synthesis and Medicine, Wiley-VCH, Wein-
heim, 2011, and references cited therein.
[18] For recent reviews, see: a) V. Ritleng, C. Sirlin, M.
Pfeffer, Chem. Rev. 2002, 102, 1731; b) J. Hassan, M.
Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev.
2002, 102, 1359; c) H. M. L. Davies, R. E. J. Beckwith,
Chem. Rev. 2003, 103, 2861; d) X. Chen, K. M. Engle,
D.-H. Wang, J.-Q. Yu, Angew. Chem. 2009, 121, 5196;
Angew. Chem. Int. Ed. 2009, 48, 5094; e) D. Alberico,
M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174;
f) I. V. Seregin, V. Gevorgyan, Chem. Soc. Rev. 2007,
36, 1173; g) T. W. Lyons, M. S. Sanford, Chem. Rev.
2010, 110, 1147; h) Y. J. Park, J.-W. Park, C.-H. Jun,
Acc. Chem. Res. 2008, 41, 222; i) L. C. Lewis, R. G.
Bergman, J. A. Ellman, Acc. Chem. Res. 2008, 41, 1013;
j) O. Daugulis, H.-Q. Do, D. Shabashov, Acc. Chem.
[7] For the synthesis of aryl halides, see: a) T. Furuya,
H. M. Kaiser, T. Ritter, Angew. Chem. 2008, 120, 6082;
Angew. Chem. Int. Ed. 2008, 47, 5993; b) T. Furuya, T.
Ritter, J. Am. Chem. Soc. 2008, 130, 10060; c) T.
Furuya, T. Ritter, Org. Lett. 2009, 11, 2860; d) G. W.
Kabalka, M.-L. Yao, J. Organomet. Chem. 2009, 694,
1638; e) M.-L. Yao, M. S. Reddy, L. Yong, I. Walfish,
D. W. Blevins, G. W. Kabalka, Org. Lett. 2010, 12, 700;
f) L. Yong, M.-L. Yao, J. F. Green, H. Kelly, G. W. Ka-
balka, Chem. Commun. 2010, 46, 2623; g) R. H. Szumi-
gala, P. N. Devine, D. R. Gauthier, R. P. Volante, J.
Org. Chem. 2004, 69, 566; h) C. Thiebes, G. K. S. Pra-
kash, N. A. Petasis, G. A. Olah, Synlett 1998, 141; i) H.
6
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

À
Functionalizations of Aryl C H Bonds in 2-Arylpyridines via Sequential Borylation
Res. 2009, 42, 1074; k) L. Ackermann, R. Vicente,
A. R. Kapdi, Angew. Chem. 2009, 121, 9976; Angew.
Chem. Int. Ed. 2009, 48, 9792; l) B.-J. Li, S.-D. Yang,
Z.-J. Shi, Synlett 2008, 949; m) A. S. Dudnik, V. Ge-
vorgyan, Angew. Chem. 2010, 122, 2140; Angew. Chem.
Int. Ed. 2010, 49, 2096; n) T. Satoh, M. Miura, Chem.
Eur. J. 2010, 16, 11212; o) T. Satoh, M. Miura, Synthesis
2010, 3395; p) C. Jia, T. Kitamura, Y. Fujiwara, Acc.
Chem. Res. 2001, 34, 633; q) J. A. Labinger, J. E.
Bercaw, Nature 2002, 417, 507; r) F. Kakiuchi, N. Chata-
ni, Adv. Synth. Catal. 2003, 345, 1077; s) A. R. Dick,
M. S. Sanford, Tetrahedron 2006, 62, 2439; t) Z. Li,
D. S. Bohle, C.-J. Li, Proc. Natl. Acad. Sci. USA 2006,
103, 8928; u) D. A. Colby, R. G. Bergman, J. A. Ellman,
Chem. Rev. 2010, 110, 624.
[19] a) I. A. I. Mkhalid, J. H. Barnard, T. B. Marder, J. M.
Murphy, J. F. Hartwig, Chem. Rev. 2010, 110, 890; b) P.
Nguyen, H. P. Blom, S. A. Westcott, N. J. Taylor, T. B.
Marder, J. Am. Chem. Soc. 1993, 115, 9329; c) J.-Y.
Cho, M. K. Tse, D. Holmes, R. E. Maleczka, M. R.
Smith III, Science 2002, 295, 305; d) T. M. Boller, J. M.
Murphy, M. Hapke, T. Ishiyama, N. Miyaura, J. F. Hart-
wig, J. Am. Chem. Soc. 2005, 127, 14263.
[20] N. Ishida, T. Moriya, T. Goya, M. Murakami, J. Org.
Chem. 2010, 75, 8709.
[21] a) H. Zhao, H. Fu, R. Qiao, J. Org. Chem. 2010, 75,
3311; b) I. E. Markꢃ, P. R. Giles, M. Tsukazaki, S. M.
Brown, C. J. Urch, Science 1996, 274, 2044; c) E. T. T.
Kumpulainen, A. M. P. Koskinen, Chem. Eur. J. 2009,
15, 10901.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
These are not the final page numbers!

FULL PAPERS
À
8 Functionalizations of Aryl C H Bonds in 2-Arylpyridines
via Sequential Borylation and Copper Catalysis
Adv. Synth. Catal. 2012, 354, 1 – 8
Liting Niu, Haijun Yang, Daoshan Yang, Hua Fu*
8
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!