Biomedical Engineering Reference
In-Depth Information
CO
2
Ph
O
CO
2
Ph
TrocHN
N
Pd
2
(dba)
3
P(
o
Tol)
3
K
2
CO
3
PhMe, reflux
48%
TrocHN
O
HN
N
5 steps
I
HO
N
NCbz
NHCbz
Me
Me
H
N
NH
O
Me
N
Me
O
Me
Me
O
29
30
(
−
)-Asperlicin
SCHEME 3.13
Synthesis of (
)-asperlicin by Snider and coworkers.
Buchwald and coworkers devised a one-pot Pd-catalyzed Fischer indole
synthesis of
34
and a two-step synthesis of
N
-arylindoles
36
through the bis-arylation
of
, respectively. The protocol
described by Barluenga and coworkers involved a Pd-catalyzed coupling between
o
-dihalobenzenes or
o
-chloroarylsulfonates
32
followed by a Fischer-type cyclization of
35
37
and imines
38
in an elegant amina-
tion-Heck sequence.
Other very convenient Pd-assisted methods for indole synthesis were devised
by Hegedus coworkers [36] via an intramolecular amination of monoolefins, by
Larock and coworkers [37] by coupling 2-iodoanilines with alkynes, by Chen and
coworkers [38] via annulation between 2-iodoanilines and ketones, and by Zhu and
Jia [39] by annulations of 2-haloanilines with aldehydes (Scheme 3.15). Some more
elaborated natural compounds in which these protocols were applied for building
the indole ring are shown in Scheme 3.16 [40].
Buchwald and coworkers:
NH
2
N
Me
Me
Br
R
1
Ph
Ph
31
32
O
PPh
2
Xantphos
L2
PPh
2
Pd(OAc)
2
L2
t-
BuONa
One-pot Fischer indole
synthesis
bis-arylation
Fischer cyclisation
R
1
R
1
O
O
R
3
R
3
R
3
R
1
R
3
R
1
R
2
R
2
ArBr
R
2
R
2
TsOH-H
2
O
ethanol reflux
NH
TsOH-H
2
O
ethanol reflux
N
N
N
N
N
Ar
H
Ar
54-92%
68-80%
Ph
Ph
Ph
Ph
34
33
35
36
Barluenga and coworkers:
R
3
R
1
Pd
2
(dba)
3
L1
t-
BuONa or
t-
BuOLi
dioxane, 110°C
X
N
R
R
2
R
R
2
N
Y
R
3
R
1
37
38
36-93%
39
X = Br, I, Cl, ONf, OTf
Y = Cl, Br
R = H, OBn, OMe, F
SCHEME 3.14
Indoles syntheses by Buchwald and Barluenga groups.
Search WWH ::
Custom Search