Biomedical Engineering Reference
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Me
intramolecular
Ullmann
coupling
O
Claisen
rearrangement
O
I
OH
N
MOM
Br
N
MOM
Br
Me
Me
MOM
Br
CuCl,
L12
NaOMe/MeOH
triglyme
100 °C
94
95
96
Me
9 steps
NMe
H
O
deprotection
N
MOM
Br
N
Br
O
Me
69%
H
Br
98
97
(
−
)-Flustramine B
SCHEME 3.36
Kobayashi and coworkers' one-pot sequential intramolecular Ullmann
coupling/Claisen rearrangement/deprotection in the total synthesis of (
)-flustramine B.
When devising the total synthesis of vancomycin [97]. Nicolaou and
coworkers used an original and efficient copper-mediated (2-5 equiv of copper
source) intramolecular arylation of phenols via the strategic incorporation of a
triazeneunitatthe
ortho
position of a leaving group on the aromatic ring
(Scheme 3.37) [98]. This auxiliary will act both as a potential “electron sink”
and as a coordinating site.
N
N
PhOH, CuBr
S(Me)
2
K
2
CO
3
MeCN/Py 5:1
80°C, 2 h
⋅
N
N
N
N
Br
Br
PhO
OPh
91%
Br
Br
Me
OH
Intramolecular
C-O bond 1 formation:
CuBr
Intramolecular
C-O bond 2 formation:
CuBr
O
NH
3
S(Me)
2
, K
2
CO
3
MeCN/Py, reflux
(67%)
⋅
HO
HO
S(Me)
2
, K
2
CO
3
MeCN/Py, reflux
(74%)
⋅
O
Me
O
C-O bond 2
O
C-O bond 1
HO
Cl
•
•
O
O
•
•
HO
OH
Cl
O
O
O
N
N
O
NHMe
H
H
H
H
H
H
O
O
Me
HN
O
O
2
C
NH
2
Me
H
OH
OH
Vancomycin
HO
SCHEME 3.37
Total synthesis of vancomycin using a Cu-mediated intramolecular arylation
by Nicolaou and coworkers.
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