Biomedical Engineering Reference
In-Depth Information
(a)
Traditional methods for the preparation of ArB(OR)
3
(d)
Ir(I)-catalyzed direct C-H borylation (catalytic cycle)
Mg(0)
or
R'Li
then B(OR'')
3
or
cat. Pd(0), base
[B(OR'')
2
]
2
or
HB(OR'')
2
[Ir(COD)Cl]
2
B(OR'')
2
X
R
R
dtbpy
B
2
pin
2
(X = I, Br)
N
Bpin
Ir
(b)
Transition metal-catalyzed direct C-H borylation
H
Bpin
N
Bpin
H
Bpin
cat. TM (Ir, Rh, Fe)
B
2
pin
2
oxidative
addition
H
Bpin
oxidative addition
-
reductive elimination
B
2
pin
2
or HBpin
R
R
N
H
(c)
Ir(I)-catalyzed direct C-H borylation of heteroarenes
Ir
H
N
Bpin
Bpin
Bpin
N
Bpin
Y = N-TIPS
Ir
cat. [Ir(COD)Cl]
2
cat. dtbpy
B
2
pin
2
H
N
Bpin
Bpin
Y
reductive
elimination
H
Y = NH, S, O
Y
electron-rich heteroarenes
Bpin
Y
Bpin
H
t
-Bu
t
-Bu
Bpin
cat. [Ir(COD)Cl]
2
cat. dtbpy
H
Bpin
NN
+
B
2
pin
2
N
N
N
H
N
N
dtbpy
electron-poor heteroarenes
1
:
2
SCHEME 1.23
Transition metal-catalyzed C-H borylation.
(Scheme 1.23a). A recent alternative involves the transition metal-catalyzed direct
borylation of simple arene C-H bonds (Scheme 1.23b) [77].
While iron and rhodium have been reported to effect sp
2
C-H borylation,
iridium-based catalysts have beenmore extensively investigated. In 1999, Iverson and
Smith disclosed the borylation of deuterated benzene in the presence of excess HBpin
catalyzed by Cp
Ir complexes [78]. Since then, more active catalyst combinations
have been developed, consisting of an iridium precatalyst and, for example a,
phosphine- [79] or bipyridine-derived [80] ligands for example. The regioselectivity
of these reactions is predominantly controlled by steric effects, with the least hindered
C-H bond typically reacting. As a result, this provides complementary products to
those obtained using more conventional methods for which the regioselectivity is
driven by electronic effects (S
E
Ar) or directing groups (such as directed
ortho
-
metalation [81]. It should, however, be noted that directing groups can also be used in
direct C-H borylation to provide
ortho
-borylated arenes [82].
C-H borylation of
p
-electron-rich and electron-deficient heteroarenes has also
been investigated. Treatment of thiophene, furan, pyrrole, and indole derivatives with
B
2
pin
2
and catalytic [Ir(COD)Cl]
2
/dtbpy (dtbpy
di-
tert
-butylbipyridine) selec-
tively provides C2 borylated heteroarenes (Scheme 1.23c) [83]. A reversal in
regioselectivity favoringC3 borylation is observedwhen bulky
N
-substituted pyrroles
and indoles are subjected to the same reaction conditions. This result capitalizes on
previous observations of slower reaction rates for borylation at sterically encumbered
C-H bonds (i.e., control of regioselectivity based on steric effects). In the case of
p
-deficient heteroarenes, such as pyridine, slightly higher reaction temperatures are
required (100
C instead of 80
C) for C-H borylation to occur in good yield
(Scheme 1.23c). Unfortunately, product mixtures are usually obtained; in the case
of pyridine, for example, a 2:1 ratio of 3- and 4-borylpyridine is observed. Although
¼
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