Biomedical Engineering Reference
In-Depth Information
coworkers [50] and tetrahydroquinoline alkaloid martinellic acid by Ma and
coworkers [51] are other recent examples that illustrate such a strategy. Although
the reactions can be usually carried out in the absence of ligands, in some cases
catalytic amounts of copper salts (CuI in 10mol% loading for benzolactam V8 and
CuI in 20mol% for SB-214857) could be used. For martinellic acid, a stoichiometric
amount of CuI was necessary.
3.3.5.2. Aryl amidation Amides and carbamates are also considered as good
nucleophiles for copper-catalyzed cross-coupling reactions with aryl halides,
especially after the introduction of ligands in the reaction medium that afforded
milder protocols for natural product syntheses. By reaction of the aryl bromide
55
with the amide subunit
was obtained in 82% yield
(Scheme 3.24). Eight additional steps were required for forging the elaborated
54
, aromatic fragment
56
O
O
O
O
or
or
Ar
X
Y
NH
Y
N
Ar
R
1
R
1
NH
2
NH
Ar
Y = C, O; R
1
= alkyl; Ar = aryl; X = I, Br, Cl
O
OMe
OTBS
OMe
OMe
H
2
N
54
CuI,
L7
, K
2
CO
3
PhMe, 110°C
82%
8 steps
Me
NH
OMe
NH
PhO
2
S
OMe
OMe
Me
O
TIPSO
O
TBSO
Br
OMe
TBSO
OMe
PhO
2
S
OMe
55
56
57
Macrocyclic core of cytotrienins
Y
CuI,
L7
, K
2
CO
3
dioxane, 110°C
( 85-80%)
Me
F
NH
O
Me
O
Me
Y
O
O
N
N
O
HO
N
O
O
OMe
N
OH
HN
Cytotrienins A-D
(Y = OH or Y = O)
O
(
±
)-Linezolid
(
±
)-Toloxatone
O
O
Me
Cu powder, K
2
CO
3
o
-xylene, 140-150°C
(53%)
CuI,
L7
, K
2
CO
3
dioxane, reflux
(97%)
CuI,
L8
, K
2
CO
3
dioxane, 140°C
sealed tube
(37%)
CF
3
O
N
O
Me
NMe
2
N
NHPr
Me
H
O
HO
N
N
Nu =
H
2
N
Me
CF
3
CF
3
H
H
O
H
Vasicoline
CJ-15161
Dutasteride
H
SCHEME 3.24
Selected examples of Cu-mediated arylation of amides (for the structures of
copper ligands, see Scheme 3.22).
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