Chemistry Reference
In-Depth Information
Br
Br
Br
1. Br
2
, CCl
4
2. PPh
3
CH
2
O, Et
3
N
PPh
3
NO
2
NO
2
NO
2
6.40
6.41
6.42
Br
Br
Pd(MeCN)
2
Cl
2
BQ
1) Hg(OAc)
2
2) I
2
1) Fe, HOAc
2
) TsCl, py
N
NHTs
6.39
6.43
Ts
OH
AcHN
CO
2
Me
Br
I
1) Pd(OAc)
2
, Et
3
N
AcHN
CO
2
Me
(MeCN)
2
PdC
l
2
HO
2) Pd(OAc)
2
, Et
3
N
N
Ts
N
6.38
6.44
Ts
OH
Ac
CO
2
Me
HO
ClPd
AcHN
CO
2
Me
N
Cl
2
Pd
N
Ts
N
6.45
6.46
Ts
Ac
CO
2
Me
H
N
CO
2
Me
N
NaBH
4
,
Na
2
CO
3
,
h
ν
N
Ts
N
H
6.47
6.37
Scheme 6.18
The metal-catalysed cyclization of
o
-alkynyl anilines to indoles and
o
-alkynylphenols to benzofurans has
been studied (Scheme 6.19).
17
It is a useful method because the starting materials are readily available by
Sonogashira reactions (Section 2.8). Cyclization followed by protonolysis of the
1
-intermediate
6.51
gives
the heterocycle. As protonolysis regenerates a palladium(II) species, no added oxidant is required. In some
cases, protonolysis is slow, and the reaction must be carried out in acidic conditions.
18
In terms of synthetic planning, it must be noted that a transition-metal catalyst is not required for this
cyclization.
o
-Alkynylamines can be cyclized to indoles under basic conditions, especially if the nitrogen atom
has an electron-withdrawing substituent to lower the pK
a
. Just such a base-catalysed cyclization was employed
in a synthesis of goniomitine (Scheme 6.20),
19
after a Sonogashira reaction was employed to synthesize the
substrate. Similarly, benzofurans are easily prepared by base catalysed cyclization as in a synthesis of
Ailanthoidol (Scheme 2.115). The transition-metal catalysed cyclization is of particular importance when
