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CN
N
M
PG
Pd(OAc)
2
(10 mol%)
Phen (10 mol%)
Cs
2
CO
3
(1 equiv)
toluene, 160 °C, 48h
Ph
H
N
base
N
N
Metal
N
N
PG
N
PG
PG
Scheme 12.32 Challenges in C3 arylation of indazole.
H
Ar
Pd (OAc)
2
(10 mol%), phen (10 mol%)
Cs
2
CO
3
(1 equiv), toluene
N
N
Ar
X
N
N
R
R
Scheme 12.33 Arylation of indazoles at the C3 position.
R
3
Br
H
R
2
R
2
PdCl(PPh
3
)
2
Cl
2
Bu
4
NaOAc
N
N
+
N
N
R
1
R
1
NMP, 100
°
C
N
N
R
3
2-24h
Scheme 12.34 Arylation of triazoles at the C5 position.
developing a new method for C3 arylation of 1H-indazole is dicult because
the N--N bond has a tendency to hydrolyze in the presence of metal and
base. Another problem is second C-H activation when the nitrogen at the
2-position of indazole ring can direct further arylation on the newly installed
aryl group (Scheme 12.32).
To solve these problems, Yu and co-workers initially applied the previous
conditions of C3 arylation of pyridines
60
on N-methylindazole using PhI as
the coupling partner. Unfortunately, only a 24% yield of desired product was
obtained along with 3% of undesired product from further directed aryla-
tion. Subsequent optimization produced the desired compound in 93% yield
(Scheme 12.33).
1,2,3-Triazole, a multiple heteroatomic heterocycle, was also arylated
by Gevorgyan and co-workers using palladium.
61
Under the reaction con-
ditions, aryl bromides were used as the coupling partner (Scheme 12.34).
Further, in case of thiazoles, C2, C4 and C5 arylations were achieved at
ambient temperature. In this case, azole N-oxides were used as the substrate
and the
selectivity
obtained depended on the
substrate design
(Scheme 12.35).
64
In case of simple heteroaromatics such as pyrrole, furan and thiophene,
regioselective palladium-catalyzed arylations are also known. In 2009,
Fagnou and co-workers reported the coupling reaction between heterocyclic
compounds and an aryl bromide coupling partner (Scheme 12.36).
62
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