Synthesis of pyridine-borane complexes via electrophilic aromatic borylation

Article abstract of DOI:10.1021/jo101920p

Pyridine-borane complexes were synthesized from 2-arylpyridines through an electrophilic aromatic borylation reaction with BBr₃. The intermediate 2-(2-dibromoborylaryl)pyridines were stable enough to be handled in air and served as the syntheti

Full text of DOI:10.1021/jo101920p

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of alkynylborates equipped with a tertiary pyridinium moiety.2
Synthesis of Pyridine-Borane Complexes via
Electrophilic Aromatic Borylation
The rearrangement reaction successfully afforded various
aza-π-conjugated materials having a boron-nitrogen coor-
dination bond, which exhibited interesting properties such as
strong fluorescence. We then looked for a more straightfor-
ward synthetic access to an analogous structural motif.
Herein is described a facile synthetic method of pyridine-
borane complexes via an electrophilic aromatic borylation
reaction of 2-phenylpyridine derivatives with BBr3.
Naoki Ishida,† Taisaku Moriya,† Tsuyoshi Goya,‡ and
Masahiro Murakami*,†
†Department of Synthetic Chemistry and Biological
Chemistry, Kyoto University, Katsura,
Kyoto 615-8510, Japan, and ‡Advanced Materials Research
Center, Nippon Shokubai Co., Ltd., 5-8, Nishi Otabi-cho,
Suita, Osaka 564-0034, Japan
Boron trihalides are known to borylate aromatic hydro-
carbons with assistance of nitrogen directing groups.3 For
instance, 2-phenylbenzimidazole reacts with BCl3 at 300 °C
to give 2-(2-borylphenyl)benzimidazole.4 1-Amino-2-phe-
nylbenzene reacts with BCl3 in the presence of AlCl3 to
provide 10-chloro-9,10-azaboraphenathrene.5 We envisaged
that the pyridine moiety of 2-arylpyridines would act as a
directing group6 to promote a regioselective C-H borylation
reaction with boron trihalides. The resulting pyridine-
dihaloborane complexes would work as precursory plat-
forms for various pyridine-borane complexes, which are
potent light-emitting materials possessing a low-lying LUMO
level. Thus, a reaction of 2-phenylpyridine (1) with BCl3 and
BBr3 was examined. When 2-phenylpyridine (1) was treated
with 3.0 equiv of BBr3 and 1.0 equiv of Et2N(i-Pr) in
dichloromethane at roomtemperature, pyridine-dibromoborane
complex 2 was obtained in 89% yield. On the other hand,
BCl3 failed to afford the corresponding borylated product
under the same reaction conditions. The product 2 was stable
toward air and moisture, making it easy to handle for further
transformations.
murakami@sbchem.kyoto-u.ac.jp
Received September 30, 2010
Pyridine-borane complexes were synthesized from
2-arylpyridines through an electrophilic aromatic boryla-
tion reaction with BBr3. The intermediate 2-(2-dibromo-
borylaryl)pyridines were stable enough to be handled in
air and served as the synthetic platform for variously
substituted pyridine-borane complexes. This facile method
would be useful for the synthesis of aza-π-conjugated
materials having boron-nitrogen coordination.
Aza-π-conjugated frameworks containing an intramolec-
ular boron-nitrogen coordination bond have attracted sig-
nificant attention owing to their interesting photophysical
and electronic properties.1 For example, 2-(3-boryl-2-thienyl)-
thiazole derivatives exhibit higher electron affinity than
conventional electron-transporting materials like tris(8-
hydroxyquinoline)aluminum (Alq3) and 2-(4-biphenyl)-5-(4-
tert-butylphenyl)-1,3,4-oxadiazole (PBD), which indicates
their potential as n-type semiconducting materials.1a Such
coordination compounds have been synthesized through
lithiation of bromo-substituted N-heteroaromatics with
n-butyllithium followed by a substitution reaction with
haloborane derivatives. However, the highly nucleophilic
and basic character of organolithium reagents may cause
undesired side reactions, limiting the range of structural
modifications. Thus, development of new synthetic methods
for aza-π-conjugated frameworks which dispense with the use
of organolithium intermediates are desired. Recently, we have
developed the palladium-catalyzed rearrangement reaction
A plausible reaction mechanism for the formation of 2 is
depicted in Scheme 1. The Lewis basic nitrogen atom of pyridine
coordinates to the Lewis acidic boron center to provide the
complex A. Another BBr3 abstracts a bromide anion from the
complex A, giving trivalent cationic boron species B (borenium
ion).7,8 Then, the cationic boron center of B electrophilically
attacks the neighboring aromatic moiety,9 and the following
rearomatization furnishes pyridine-dibromoborane complex 2.
Various aryl-N-heteroaromatics were successfully bory-
lated by treatment with BBr3 (Table 1). Bromo groups on the
SCHEME 1. Plausible Mechanism of Electrophilic Aromatic
Borylation
(1) (a) Wakamiya, A.; Taniguchi, T.; Yamaguchi, S. Angew. Chem., Int.
Ed. 2006, 45, 3170. (b) Yoshino, J.; Kano, N.; Kawashima, T. Chem.
Commun. 2007, 559. (c) Loudet, A.; Burgess, K. Chem. Rev. 2007, 107,
4891. (d) Baik, C; Hudson, Z. M.; Amarne, H.; Wang, S. J. Am. Chem. Soc.
2009, 131, 14549.
(2) Ishida, N.; Narumi, M.; Murakami, M. Org. Lett. 2008, 10, 1279.
DOI: 10.1021/jo101920p
r
Published on Web 11/23/2010
J. Org. Chem. 2010, 75, 8709–8712 8709
2010 American Chemical Society

Ishida et al.
JOCNote
TABLE 1. Electrophilic Aromatic Borylation Reactions of 2-Arylpyr-
idine Derivativesa
TABLE 2. Synthesis of Various Pyridine-Borane Complex Derivativesa
aReaction conditions: 3.0 equiv of BBr3, 1.0 equiv of Et2N(i-Pr),
CH2Cl2 (0.2 M), 0 °C to rt.
aryl group remained intact under the reaction conditions to
give tetrabromo compound 4 in 82% yield (entry 1). The
substrate 5 having a pyrimidine group, which was less basic
than pyridine, successfully participated in the borylation reac-
tion (entry 2). A sterically demanding quinoline group also
worked as the directing group to afford the corresponding
dibromoborane complex 8 in 81% yield (entry 3). 2-(2-
Pyridyl)benzothiophene (9) was borylated at the thiophene
a2.1 equiv of LiAlH4, Et2O, 0 °C to rt, 1 h. b2.1 equiv of R3Al, toluene,
rt. c2.1 equiv of R2Zn, toluene, 70 °C. dA mixture of CH2Cl2 and toluene
was used as solvent.
(3) Onak, T. In Organoborane Chemistry, Organometallic Chemistry, A
Series of Monographs; Academic Press, Inc.: New York, 1975.
(4) Letsinger, R. L.; MacLean, D. B. J. Am. Chem. Soc. 1963, 85, 2230.
(5) Dewar, M. J. S.; Kubba, V. P.; Pettit, R. J. Chem. Soc. 1958, 3073.
(6) Pyridine-directed direct C-H functionalization reactions: (a) Kakiuchi,
F.; Kochi, T. Synthesis 2008, 3013. (b) Ackermann, L.; Vicente, R.; Kapdi, A. R.
Angew. Chem., Int. Ed. 2009, 48, 9792. (c) Colby, D. A.; Bergman, R. G.;
Ellman, J. A. Chem. Rev. 2010, 110, 624. (d) Lyons, T. W.; Sanford, M. S. Chem.
Rev. 2010, 110, 1147.
moiety, resulting in the formation of complex 10 in 87% yield
(entry 4). 2-(2-Naphthyl)pyridine (11) gave a regioisomeric
mixture of 12 and 13 (3:1) in 89% combined yield (entry 5).
The 1-position of the naphthyl group was preferentially
borylated over the 3-position, as were the cases with con-
ventional electrophilic aromatic substitution reactions of
naphthalenes. This regiochemical outcome could be ascribed
to the stability of the cationic species corresponding to the
intermediate C. The cation formed by 1-borylation is more
stable than the cation formed by 3-borylation.
€
€
(7) Reviews: (a) Kolle, P.; Noth, H. Chem. Rev. 1985, 85, 399. (b) Piers,
W. E.; Bourke, S. C.; Conroy, K. D. Angew. Chem., Int. Ed. 2005, 44, 5016.
(8) (a) Ryschkewitsch, G. E.; Miller, V. R. J. Am. Chem. Soc. 1973, 95,
2836. (b) Cowley, A. H.; Lu, Z.; Jones, J. N.; Moore, J. A. J. Organomet.
Chem. 2004, 689, 2562. (c) Uddin, M. K.; Nagano, Y.; Fujiyama, R.;
Kiyooka, S.-i.; Fujio, M.; Tsuno, Y. Tetrahedron Lett. 2005, 46, 627. (d)
Chiu, C.-W.; Gabbai, F. P. Organometallics 2008, 27, 1657.
Pyridine-dibromoborane complexes thus obtained were
next treated with organometallic reagents to substitute the bromo
groups on boron with hydrogens or carbon substituents
(9) De Vries, T. S.; Prokofjevs, A.; Harvey, J. N.; Vedejs, E. J. Am. Chem.
Soc. 2009, 131, 14679.
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Ishida et al.
JOCNote
(Table 2). Treatment ofLiAlH4 in Et2O gave borohydride 14 in
80% yield (entry 1). The reaction of pyridine-dibromoborane
complexes with triorganylaluminum reagents such as Me3Al,
Et3Al, Ph3Al, and (n-Oct)3Al rapidly proceeded at room
temperature to complete within 5 min. The corresponding
alkylated products were isolated in yields ranging from 74 to
91% (entries 2, 3, 5, and 9-13). Diorganylzincs were also
effective, although the alkylation/arylation reaction was
slower than that with triorganylaluminum reagents (entries
4 and 6-8). On the other hand, PhMgBr gave an inferior
result (43% yield of 18), and PhLi afforded a complex
mixture. PhSnBu3 and PhCu species failed to afford the
desired product.
SCHEME 2. Reactions of 22a
Next, functionalization and extension of the aromatic
chain were examined using pyridine-borane complex 22 as
the model substrate (Scheme 2). The palladium-catalyzed
Suzuki-Miyaura coupling reaction of 22 with phenylboro-
nic acid (2.0 equiv) successfully proceeded to give diarylated
product 28 in 82% yield. The boryl group coordinated by the
pyridine moiety remained intact under the reaction condi-
tions. Amination of 22 with diphenylamine was catalyzed by
Pd2dba3 CHCl3 and P(t-Bu)3,10 providing diaminated prod-
3
aKey: (a) 5 mol % of Pd(PPh3)4, 2.0 equiv of PhB(OH)2, 2.0 equiv of
uct 29 in 74% yield. When 22 was treated with 2.1 equiv of
n-BuLi in THF, dilithiated pyridine-borane complex was
generated by double bromine-lithium exchange. A subse-
quent reaction with i-PrOBpin (4.0 equiv) afforded diboro-
nic ester 30 in 54% isolated yield. On the other hand, when
1.1 equiv of n-BuLi was used in Et2O, selective monolithia-
tion on the pyridine ring took place, and a subsequent
reaction with i-PrOBpin (2.0 equiv) furnished monoboronic
ester 31 in 64% yield.
Finally, bridged teraryl 34 was synthesized from 1,4-di-
(2-pyridyl)benzene (32). Electrophilic aromatic borylation of
32 occurred at the two positions of the benzene ring which
were para to each other to afford diborylated product 33 in
73% yield (eq 2). Then, 33 was treated with trimethylalumi-
num in toluene to provide tetramethylated product 34 in
71% yield (eq 3).
Na2CO3, toluene, H2O, 90 °C; (b) 5 mol % of Pd2dba3 CHCl3, 40 mol %
3
of P(t-Bu3), 3.0 equiv of Ph2NH, 10 equiv of NaO-t-Bu, toluene, 100 °C;
(c) 2.1 equiv of n-BuLi, THF, -78 °C; then 4.0 equiv of (i-PrO)Bpin, rt;
(d) 1.1 equiv of n-BuLi, Et2O, -78 °C; then 2.0 equiv of (i-PrO)Bpin, rt.
they are expected as air-stable light-emitting materials.12
Studies on photophysical properties and application to
optoelectronic devices are now underway and will be re-
ported elsewhere.
In conclusion, we have developed a synthetic method for
pyridine-borane complexes via an electrophilic aromatic
borylation reaction with BBr3 followed by substitution
reactions with organometallic reagents. This facile method
would be useful for the synthesis of aza-π-conjugated mate-
rials having boron-nitrogen coordination.
Experimental Section
Electrophilic Aromatic Borylation of 2-Phenylpyridine (eq 1):
A General Procedure. To a stirred solution of 2-phenylpyridine
(77.6 mg, 0.5 mmol) and i-Pr2NEt (64.6 mg, 0.5 mmol) in
CH2Cl2 (0.5 mL) at 0 °C was added BBr3 (1.0 M in CH2Cl2,
1.5 mL, 1.5 mmol). Caution: BBr3 is highly moisture sensitive and
decomposes in air with an evolution of corrosive HBr. It should be
handled in a well-ventilated hood. After being stirred at room
temperature for 24 h, saturated K2CO3 aqueous solution was
added to the reaction mixture. The organic layer was separated
and extracted with CH2Cl2 (twice), washed with water (once)
and brine (once), dried over MgSO4, and concentrated. The
resulting solid was collected by filtration and washed with
hexane to give pyridine-borane complex 2 (145 mg, 0.45 mmol,
89% yield): 1H NMR δ 7.42 (t, J = 7.5 Hz, 1H), 7.55-7.60 (m,
2H), 7.75 (d, J = 7.8 Hz, 1H), 7,87 (d, J = 7.5 Hz, 1H), 7.93 (d,
J = 7.8 Hz, 1H), 8.16 (t, J = 7.8 Hz, 1H), 8.95 (d, J = 5.4 Hz,
1H); 13C NMR δ 118.5, 121.9, 123.6, 128.7, 130.7, 133.17,
133.24, 143.7, 144.4, 155.9; 11B NMR δ -1.1; HRMS (EI) calcd
for C11H7BBr2N (M - H)þ 321.9039, found 321.9052. Anal.
Calcd for C11H8BBr2N: C, 40.68; H, 2.48; Br, 49.20; N, 4.31.
Found: C, 40.61; H, 2.60; Br, 48.94; N 4.31.
The synthesized pyridine-boranes exhibited high elec-
tron affinity, which indicates such π-materials have low-
lying LUMO level. In addition, strong fluorescence in the
solid state as well as in solution was observed.11 Therefore,
(10) Nishiyama, M.; Yamamoto, T.; Koie, Y. Tetrahedron Lett. 1998, 39,
617.
(11) Very recently, photophyical and electrochemical properties of some
compounds were reported: Amarne, H.; Baik, C.; Murphy, S. K.; Wand, S.
Chem.;Eur. J. 2010, 16, 4750.
Alkylation of Pyridine-Borane Complex 2 with Me3Al (Table 2,
Entry 2): A General Procedure. To a stirred solution of 2 (32.5
mg, 0.10 mmol) in toluene (1.0 mL) at room temperature was
(12) Anthopoulos, T. D.; Anyfantis, G. C.; Papavassiliou, G. C;
de Leeuw, D. M. Appl. Phys. Lett. 2007, 90, 122105.
J. Org. Chem. Vol. 75, No. 24, 2010 8711

Ishida et al.
JOCNote
added Me3Al (1.1 M in hexane, 0.2 mL, 0.22 mmol). After being
stirred at this temperature for 5 min, the reaction was quenched
by adding water. The organic layer was separated and extracted
with AcOEt (twice), washed with water (once) and brine (once),
dried over MgSO4, and concentrated. The residue was purified
by preparative thin-layer chromatography on silica gel (eluent:
hexane/AcOEt = 2/1) to afford 15 (17.7 mg, 0.091 mmol, 91%
yield): 1H NMR δ 0.05 (s, 6H), 7.26-7.38 (m, 2H), 7.43 (td, J =
7.5, 0.9 Hz, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.84 (d,
J = 7.5 Hz, 1H), 7.93-7.99 (m, 2H), 8.44 (dt, J = 5.7, 1.2
Hz, 1H); 13C NMR δ 8.8, 117.7, 121.3, 121.5, 125.1, 129.1,
130.2, 135.0, 139.2, 142.1, 156.8; 11B NMR δ 1.1; HRMS (EI)
calcd for C13H13BN (M - H)þ 194.1141, found 194.1136.
Acknowledgment. This work was supported in part by
New Energy and Industrial Technology Development Orga-
nization (NEDO, 09C46603d).
Supporting Information Available: Experimental details,
1
structural data for all new compounds, copies of H and 13C
NMR spectra and chromatograms. This material is available
free of charge via the Internet at http://pubs.acs.org.
8712 J. Org. Chem. Vol. 75, No. 24, 2010