Synthesis of pyridine-N-oxide-borane intramolecular complexes by palladium-catalyzed reaction of 2-bromopyridine-N-oxides with alkynyltriarylborates

Article abstract of DOI:10.1021/ol2008439

Pyridine-N-oxide-borane intramolecular complexes having an aza-stilbene π-framework were synthesized by the palladium-catalyzed reaction of 2-bromopyridine-N-oxides with alkynyltriarylborates.

Full text of DOI:10.1021/ol2008439

ORGANIC
LETTERS
2011
Vol. 13, No. 12
3008–3011
Synthesis of Pyridine-N-oxideꢀBorane
Intramolecular Complexes by Palladium-
Catalyzed Reaction of 2-Bromopyridine-
N-oxides with Alkynyltriarylborates
Naoki Ishida, Wataru Ikemoto, Mizuna Narumi, and Masahiro Murakami*
Department of Synthetic Chemistry and Biological Chemistry, Kyoto University,
Katsura, Kyoto 615-8510, Japan
murakami@sbchem.kyoto-u.ac.jp
Received April 1, 2011
ABSTRACT
Pyridine-N-oxideꢀborane intramolecular complexes having an aza-stilbene π-framework were synthesized by the palladium-catalyzed reaction of
2-bromopyridine-N-oxides with alkynyltriarylborates.
Intramolecular boron complexes of nitrogen-containing
π-conjugated compounds, in which the nitrogen atom
coordinates to the boron atom suitably positioned within
the molecule, have gained increasing attention from the
viewpoint of development of new π-electron materials.1
Various aza-π-conjugated compounds including thia-
zoles,1e azobenzenes,1f pyridines,1g,i and imines1h can form
boron complexes, exhibiting unique properties such as
strong fluorescence and high electron affinity. Such intra-
molecular complexes have been synthesized through lithia-
tion of the parent aza-π-frameworks followed by a
substitution reaction with organoborane derivatives. On
the other hand, pyridine N-oxides can also form complexes
with boranes through donation of the lone pair electrons of
oxygen with their electron affinity being enhanced.2 How-
ever, such complexes have been limited to intermolecular
variants because intramolecular complexes are difficult to
synthesize. A pyridine-N-oxide moiety is vulnerable to
reagents for lithiation, and hence, the conventional lithia-
tion methods are not applicable. We previously developed
the palladium-catalyzed reactions of alkynyl(aryl)borates
with aryl halides, which gave (1,2-diarylalkenyl)boranes
stereoselectively.3 The palladium-catalyzed reaction was
extended to the rearrangement of alkynylborates bearing a
pyridinium moiety, giving pyridineꢀborane complexes
which exhibited intense fluorescence and high electron
affinity.4 During the course of our study on the deve-
lopment of new π-conjugated materials, we are then
interested in the synthesis of pyridine-N-oxideꢀborane
intramolecular complexes. Herein is described the palla-
dium-catalyzed reaction of 2-bromopyridine-N-oxides
(1) For reviews on boron-containing π-electron materials, see:
(a) Entwistle, C. D.; Marder, T. B. Chem. Mater. 2004, 16, 4574.
(b) Yamaguchi, S.; Wakamiya, A. Pure Appl. Chem. 2006, 78, 1413.
€
(c) Jakle, F. Coord. Chem. Rev. 2006, 250, 1107. (d) Loudet, A.; Burgess,
K. Chem. Rev. 2007, 107, 4891. For recent examples, see:(e) Wakamiya,
A.; Taniguchi, T.; Yamaguchi, S. Angew. Chem., Int. Ed. 2006, 45, 3170.
(f) Yoshino, J.; Kano, N.; Kawashima, T. Chem. Commun. 2007, 559.
(g) Jaska, C. A.; Piers, W. E.; McDonald, R.; Parvez, M. J. Org. Chem.
2007, 72, 5234. (h) Yoshino, J.; Kano, N.; Kawashima, T. J. Org. Chem.
2009, 74, 7496. (i) Baik, C; Hudson, Z. M.; Amarne, H.; Wang, S. J. Am.
Chem. Soc. 2009, 131, 14549.
(2) (a) Stephens, R. S.; Lessley, S. D.; Ragsdale, R. O. Inorg. Chem.
1971, 10, 1610. (b) Das, M. K.; Bandyopadhyay, S. N. Inorg. Chem.
1994, 33, 5358. (c) Uddin, M. K.; Nagano, Y.; Fujiyama, R.; Kiyooka,
S.; Fujio, M.; Tsuno, Y. Tetrahedron Lett. 2005, 46, 627. (d) Kaufmann,
L.; Vitze, H.; Bolte, M.; Lerner, H.-W.; Wagner, M. Organometallics
2008, 27, 6215. (e) Nizhnik, Y. P.; Lu, J.; Rosokha, S. V.; Kochi, J. K.
New J. Chem. 2009, 33, 2317.
(3) (a) Ishida, N.; Miura, T.; Murakami, M. Chem. Commun. 2007,
559. (b) Ishida, N.; Shimamoto, Y.; Murakami, M. Org. Lett. 2009, 11,
5434.
(4) Ishida, N.; Narumi, M.; Murakami, M. Org. Lett. 2008, 10, 1279.
(5) For palladium-catalyzed reactions of pyridine-N-oxide deriva-
tives, see: (a) Campeau, L.-S.; Rousseaux, S.; Fagnou, K. J. Am. Chem.
Soc. 2005, 127, 18020. (b) Cho, S. H.; Hwang, S. J.; Chang, S. J. Am.
Chem. Soc. 2008, 130, 9254. (c) Campeau, L.-C.; Stuart, D. R.; Leclerc,
J.-P.; Bertrand-Laperle, M.; Villemure, E.; Sun, H.-Y.; Lasserre, S.;
Guimond, N.; Lecavallier, M.; Fagnou, K. J. Am. Chem. Soc. 2009, 131,
3291. (d) Xi, P; Yang, F.; Qin, S.; Zhao, D.; Lan, J.; Gao, G.; Hy, C.;
You, J. J. Am. Chem. Soc. 2010, 132, 1822.
r
10.1021/ol2008439
Published on Web 05/23/2011
2011 American Chemical Society

with alkynyl(triaryl)borates to furnish pyridine-N-oxideꢀ
borane complexes having an aza-stilbene skeleton.5
We initially examined a reaction of 2-bromopyridine-
reaction mechanisms is depicted in Scheme 1. Oxidative
addition of 2-bromopyridine-N-oxide (1a) to palladium(0)
gives arylpalladium bromide A. The resulting arylpalla-
dium species A undergoes carbopalladation across the
alkyne moiety of the alkynylborate 2a in a cis-fashion to
afford alkenylpalladium B, with which palladium is lo-
cated on the carbon R to boron. Then, the phenyl group on
boron migrates onto the R-carbon, leaving the boron p
orbital empty.3b The migrating phenyl group attacks from
the backside of the R-carbonꢀpalladium bond, resulting in
inversion of the stereochemistry of the R sp2-carbon.10,11
The palladium(0) species is released and the oxygen atom
on the pyridine-N-oxide coordinates to boron to form the
pyridine-N-oxideꢀborane complex 3.
N-oxide hydrochloride (1a HCl), which was commercially
3
available, with ethynyltriphenylborate 2a6 and diisopro-
pylamine7 in the presence of catalytic amounts of [Pd-
(π-allyl)Cl]2 and various additional ligands (Table 1).
When P(o-tol)3 was employed as the ligand,3a pyridine-N-
oxideꢀborane complex 3 was produced in 25% yield
(entry 1). The use of XANTPhos, which was the best
ligand for the reaction of alkynyl(aryl)(9-BBN)s with aryl
halides,3b gave complex 3 in 40% yield (entry 2). When
2,20-bipyridine was used instead of phosphine ligands, the
yield was improved to 70% (entry 3). We finally found
DPEPhos gave the best result, affording 3 in 78% NMR
yield (entry 4). The pyridine-N-oxideꢀborane complex 3
thus formed was considerably more stable toward air than
ordinary triorganoboranes and was isolated in 69% yield
after column chromatography on silica gel. The stability
Scheme 1. Possible Reaction Mechanism
Table 1. Screening of Ligandsa
Next, we examined the substrate scope of the palladium-
catalyzed reaction. Both the electron-donating methoxy
group (1b) and electron-withdrawing trifluoro-methyl
group (1c) on the 5-position of the pyridine moiety have
little influence on the reactivity, resulting in the formation
of the corresponding pyridine-N-oxideꢀborane complexes
4 and 5 in 79 and 80% yield, respectively (Table 2, entries 1
and 2). 2-Bromoquinoline-N-oxide (1d) could also parti-
cipate in the reaction (entry 3). The unprotected hydroxyl
group at the 6-position of the pyridine-N-oxide 1e was
tolerated under the reaction conditions (entry 4). Pyridine-
N-oxideꢀborane complexes having a tetrasubstituted
olefin moiety 8 and 9 could be synthesized by employing
alkynyltriphenylborates 2b (R0 = Me) and 2c (R0 = Et)
instead of 2a (entries 5 and 6). Ethynyltri(p-metho-
xyphenyl)borate 2d and ethynyltri(p-fluorophenyl)borate
2e successfully provided the corresponding pyridine-N-
oxideꢀborane complexes (entries 7 and 8).
entry
ligand
P(o-tol)3
yield of 3 /%b
1
2
3
4
25
XANTPhos
2,20-Bipyridine
DPEPhos
40
70
78(69)
a Reaction conditions: 1.0 equiv of 2-bromopyridine-N-oxide hydro-
chloride (1a HCl), 1.0 equiv of ethynyltriphenylborate 2a, 1.0 equiv of
3
HN(i-Pr)2, 2.5 mol % [Pd(π-allyl)Cl]2, 6 mol % ligand, toluene, 60 °C,
1 h. b Determined by NMR analyses. Isolated yield in parentheses.
can be ascribed to the intramolecular coordination of
oxygen to boron, which was supported by an upfield shift
of the 11B NMR signal (δ = 5.0 ppm).
A number of mechanisms have been reported for the
reactions of alkynylborates with electrophilic species
which induce migration of a boron-substituent onto its R
sp-carbon.8,9 Although it is difficult to establish only one
mechanism for the formation of 3, one of the plausible
Further derivatization of the pyridine-N-oxideꢀborane
complex 3 was possible. When 3 was treated with 1.5 equiv
(10) For substitutive 1,2-migration from boron to the R-carbon with
(6) Alkynyltriarylborate 2a was synthesized by simply treating a
triphenylboraneꢀpyridine complex with ethynylmagnesium bromide
and subsequently with tetramethylammonium chloride. See Supporting
Information for detail.
(7) Diisopropylamine gave a better yield than HNEt2, Et3N, pyri-
dine, or K2CO3.
(8) A review on the reaction of organoborates with electrophiles:
Negishi, E. J. Organomet. Chem. 1976, 108, 281.
(9) (a) Zweifel, G.; Arzoumanian, H.; Whitney, C. C. J. Am. Chem.
€
inversion of stereochemistry, see: Kobrich, G.; Merkle, H. R. Angew.
Chem., Int. Ed. 1967, 6, 74.
(11) For related SN2-type substitution reactions at sp2 carbons with
inversion of configuration, see: (a) Ochiai, M.; Oshima, K.; Masaki, Y.
J. Am. Chem. Soc. 1991, 113, 7059. (b) Luccini, V.; Modena, G.;
Pasquato, L. J. Am. Chem. Soc. 1993, 115, 4527. (b) Shiers, J. J.;
Shipman, M.; Hayes, J.; Slawin, A. M. Z. J. Am. Chem. Soc. 2004,
126, 6868. (c) Ando, K.; Kitamura, M.; Miura, K.; Narasaka, K. Org.
Lett. 2004, 6, 2461. (d) Bernasconi, C.; Rappoport, Z. Acc. Chem. Res.
2009, 42, 993 and references cited therein.
€
Soc. 1967, 89, 3652. (b) Binger, P.; Koster, R. Synthesis 1974, 350.
(c) Miyaura, N.; Yoshinari, T.; Itoh, M.; Suzuki, A. Tetrahedron Lett.
1974, 15, 2961. (d) Pelter, A.; Bentley, T. W.; Harrison, C. R.;
Subrahmanyam, C.; Laub, R. J. J. Chem. Soc., Perkins 1 1976, 2419.
(12) (a) Zoltewicz, J. A.; Kauffman, G. M. J. Org. Chem. 1969, 34,
1405. (b) Taylor, S. L.; Lee, D. Y.; Martin, J. C. J. Org. Chem. 1983, 48,
4156.
Org. Lett., Vol. 13, No. 12, 2011
3009

of LDA in THF, the 6-position of the pyridine ring was
selectively deprotonated.12 Subsequent treatment with
benzaldehyde gave alcohol 12 in 96% yield (eq 1).
Table 2. Synthesis of Pyridine-N-oxideꢀBorane Complexesa
The optical and electronic properties of pyridine-N-
oxideꢀborane complexes were briefly compared with
those of pyridineꢀborane complexes (Table 3). Pyridine-
N-oxideꢀborane complex 3 exhibited no fluorescence un-
like the pyridineꢀborane complex 13.4,13 Electrochemical
data were determined by cyclic voltammetry, and both
π-conjugated compounds showed reversible reduction
waves. The N-oxide derivative 3 had a less negative reduc-
tion potential (V1/2 = ꢀ2.0 V) than 13 (V1/2 = ꢀ2.2 V),
indicating the pyridine-N-oxideꢀborane moiety was act-
ing as a stronger electron-accepting group than the corre-
sponding pyridineꢀborane moiety. Notably, the reduction
potential of 3 was less negative than the reduction peak
potential of conventional electron-transporting material
Alq3 (Vpc = ꢀ2.14 V), which shows 3 has a lower LUMO
level than Alq3.
Table 3. Photophysicala and Electrochemicalb Properties of 3
and 13
compd
λab
Log ε
λem
Φ
V1/2/Vc
3
368
359
4.14
4.17
ꢀ
0
ꢀ2.0
ꢀ2.2
13
422
0.44
a Determined in CH2Cl2. b Determined in γ-butyrolactone with
Bu4NClO4 at a scan rate of 100 mV sꢀ1
ferrocenium.
.
c Potentials vs ferrocene/
In summary, we synthesized pyridine-N-oxideꢀborane
intramolecular complexes having an aza-stilbene π-frame-
work by the palladium-catalyzed reaction of 2-bromopyr-
idine-N-oxides with alkynylborates. The pyridine-N-
oxideꢀborane complexes exhibited higher electron affi-
nities than the corresponding pyridineꢀborane complexes.
Such π-conjugated compounds having a low-lying LUMO
(13) The molar absorption coefficients of 3 and 13 are similar (log
ε = 4.14 for 3, 4.17 for 13). This indicates that the radiative lifetimes
should be similar for both compounds according to the StricklerꢀBerg
relation. Internal conversion from the excited state of the pyridine-N-
oxideꢀborane complex might be faster than that of the pyridineꢀborane
complex.
a Reaction conditions: 1.0 equiv of 1, 1.0 equiv of alkynyltriarylbo-
rate 2, 2.5 mol % [Pd(π-allyl)Cl]2, 6 mol % DPEPhos, toluene, 60 °C, 1 h.
b Isolated yield. c 1.0 equiv of HN(i-Pr)2 was added.
(14) Anthopoulos, T. D.; Anyfantis, G. C.; Papavassiliou, G. C; de
Leeuw, D. M. Appl. Phys. Lett. 2007, 90, 122105.
3010
Org. Lett., Vol. 13, No. 12, 2011

level are expected as air-stable semiconducting materials.14
Further studies on the properties and application of the
pyridine-N-oxideꢀborane complexes are ongoing.
Organization (NEDO, 09C46603d), and the Asahi Glass
Foundation.
Supporting Information Available. Experimental de-
tails, structural data for all new compounds, copies of 1H
and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was supported in part by
MEXT (Grand-in-Aid for Young Scientist (B) No. 22750038),
New Energy and Industrial Technology Development
Org. Lett., Vol. 13, No. 12, 2011
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