Biomedical Engineering Reference
In-Depth Information
Cu source
[Cu]
R-X
NuH, base
Path
A
Path
B
R[Cu]X
48
R-Nu
[Cu]Nu
50
X
R-X
R = aryl, vinyl
NuH, base
R[Cu]Nu
49
SCHEME 3.21
General mechanism for the Ullmann-type reactions.
3.3.3. Scope and Limitations
Although Cu-mediated and Cu-catalyzed cross-coupling reactions (classical Ull-
mann and related methods) were first developed during the time frame of 1903-
1906 by Ullmann and Goldberg, the last decade witnessed the main progresses
mostly based on optimization of operational conditions [47]. Indeed, the first
examples described required very harsh reaction conditions, with temperatures as
high as 210
C, with in some cases the need for stoichiometric amounts of copper
for obtaining reasonable yields. Consequently, the scope of the transformation was
very restricted. Cu catalysis remained in a latent stage for decades and only
recently the addition of appropriate ligands leading to very efficient copper
catalytic systems has paved the way to previously inaccessible transformations.
Now, mildest and more practical conditions (e.g., polar high boiling point solvents
as dimethyl sulfoxide (DMSO) or NMP could be replaced by toluene and the
reactions could be carried out at lower temperatures) and a broader, simpler, and
more accessible aryl sources could be successfully employed. In Scheme 3.22,
Some ligands
OH
N
NHR
1
O
O
Me
N
N
CO
2
H
R
2
R
2
N
NH
2
t-
Bu
t-
Bu
Me
N
NHR
1
L9
R
2
= OH
L10
R
2
= NH
2
L11
R
2
= NHMe
L12
L13
L14
L15
L7
R
1
= H
L8
R
1
= Me
L6
C-heteroatoms bond formation
O
O
R
1
Ar
Some copper precursors
R
3
N
Ar'
R
R
1
N
N
H
Ar
R
2
O
SMe
2
Cu
2
O, Cu(OAc)
2
Cu powder, CuCl
Cu(acac)
2
, Cu bronze, etc.
CuI, CuBr, CuBr
â‹…
R
2
R
2
= Ar, Alkyl
Ar
Ar O R
R = Aryl, alkyl, vinyl
NHet
SR
Het = heterocycles
SCHEME 3.22
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