LETTER
▌1413
lSetitelrver-Catalyzed Direct C–H Arylation of N-Iminopyridinium Ylides with
Arylboronic Acids
C–H Arylation of N-Iminopyridinium Ylides
Lei Fang, Xiaoyun Shi, Liangshun Chen, Jianjun Yu,* Limin Wang*
Key Laboratory of Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road,
Shanghai 200237, P. R. of China
Fax +86(21)64253881; E-mail: wanglimin@ecust.edu.cn; E-mail: jjYu@ecust.edu.cn
Received: 15.01.2014; Accepted after revision: 25.03.2014
Wu et al. also developed a new method for the arylation
Abstract: A novel direct C–H arylation of N-iminopyridinium
of pyridine N-oxides with arylboronic esters.11 Indeed, al-
ylides with arylboronic acids has been developed. This reaction is
though there has been made tremendous progress in this
area, new and efficient methods for the arylation of het-
performed at ambient temperature using inexpensive reagents: cat-
alytic silver nitrate in the presence of potassium persulfate co-oxi-
dant and give pyridyl arylation derivatives in moderate to good erocycles are still in demand. Herein we report a new ap-
yields.
proach for the C–C bond formation of N-iminopyridinium
ylides which catalyzed by silver salt at room temperature.
Key words: silver, N-iminopyridinium ylides, arylboronic acids,
arylation, room temperature
Benzoyliminopyridinium ylide and phenylboronic acid
using water–dichloromethane co-solvent system to estab-
lish the best reaction conditions (Table 1). Regioselectiv-
ity on the heterocycle was predominantly for the 2- and 4-
positions. However, unlike the literature report,10 a mix-
ture of C2 and C4 coupling products were obtained to-
gether even an excess of the the ylide relative to
phenylboronic acid coupling partner was employed. The
reaction performed better when excessive phenylboronic
acid was used (Table 1, entries 1–4). Using 1.5 equiva-
lents of the phenylboronic acid increased the yield to 60%
(Table 1, entry 3). Further increasing the excess to 2.5
equivalents provided only a marginal improvement (62%,
Table 1, entry 4), which did not justify the large excess.
To know the effective amount of silver salt required for
catalysis, experiments with lower amounts (20–10 mol%)
as well as higher amounts (20–50 mol%) of AgNO3 did
not show any improvement in the coupling reaction (Ta-
ble 1, entries 5 and 6). In the light of recent advances in
this area, evaluation with other metal salts identified
AgNO3 as the most efficient catalyst (Table 1, entries 7–
12). As the reaction conditions involved two immiscible
substances, the addition of a phase-transfer catalyst was
tested. With 5 mol% of tetrabutylammonium bromide
(TBAB), formation of arylated products increased to 67%
(Table 1, entry 13). Moreover, the yield was slightly re-
duced when (NH4)2S2O8 was used as an oxidant (Table 1,
entry 14). The influence of solvents was also examined,
and polar solvents were not suitable in this reaction (Table
1, entry 15).
Pyridine moieties are key structural units and exist widely
in a large number of natural products, functional materi-
als, pharmaceuticals, and ligands.1 As such, there has been
significant interest in developing efficient methods for the
synthesis of these molecular architectures. These com-
pounds are typically synthesized by cross-coupling reac-
tions between 2-halopyridines and aryl organometallic
derivatives2 or by the reaction of Grignard reagents with
pyridine N-oxide as described by Almvist and Olsson.3
More recently, considerable attention has been given to
direct arylation reactions as a more efficient approach for
aryl–aryl bond formation.4 In this context, Fagnou,
Charette, Hiyama, and other groups have disclosed their
pioneering work on transition-metal-catalyzed ortho ary-
lation through C–H functionalization of pyridine N-
oxides5 or N-iminopyridinium ylides.6 This remarkable
progress avoids the utilization of stoichiometric amounts
of organometallic reagents and has made 2-aryl pyridine
derivatives easily available. However, these transition-
metal-catalyzed methods also have some limitations such
as need of a large excess of heterocyclic partners, expen-
sive ligands, and harsh reaction conditions.
In a major improvement, Baran et al. recently reported a
method7 for the cross-coupling of electron-deficient
arenes and quinines with arylboronic acids under classical
Minisci conditions. Recently, Wang et al. developed a
cheaper and environmentally friendly catalytic system8
composed of FeS and K2S2O8 for this cross-coupling reac-
tion. Then Vishwakarma et al. developed a new and effi-
cient iron catalyst9 Fe(acac)2 which was used in a catalytic
amount. In order to expand the scope and selectivity of the
reaction substrates, Mai et al. used pyridine N-oxides as
platforms to generate the 2-arylpyridines.10 Very recently,
With the optimized conditions in hand, the scope of the re-
action was investigated, and all the results are given in Ta-
ble 2. The reaction worked well even on gram scale, and
the yield decreased when phenylboronic acid pinacol ester
was used instead of phenylboronic acid (Table 1, entry 1).
The use of N-iminoquinolinium ylide successfully formed
the desired product with a similar acceptable yield (Table
2, entry 2). Other various 2-, 3-, and 4-methyl-substituted
N-iminopyridinium ylides also gave moderate yields of
arylated products, respectively (Table 2, entries 3–5).
SYNLETT 2014, 45, 1413–1418
Advanced online publication: 08.05.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1341268; Art ID: st-2014-w0038-l
© Georg Thieme Verlag Stuttgart · New York
Fang, Lei
