Chemistry Reference
In-Depth Information
Aldol
reaction
O
OH
O
O
OR'''
O
Rh
R
R''
R
R
R''
R''
R'
R'
R'
Claisen
condensation
O
O
O
O
O
Rh
O
H
O
R
R''
R
R
R''
OR'''
R''
R'
R'
R'
Scheme 4.32.
C -H insertion
α
to oxygen as surrogates for the aldol reaction and Claisen
condensation.
By generating the formal Claisen condensation product protected as a ketal, the C- H
functionalization avoids issues of rapid racemization.
4.2.4.3. Benzylic C-H Insertion
Benzylic C -H insertion is also an attractive function-
alization strategy for alkylbenzene derivatives [228]. If the benzylic position is electroni-
cally activated, as in
p
- methoxytoluene
129
(Scheme 4.33) [229], even a methyl site can
be functionalized as has been previously demonstrated for
N
- methylamines [219] . Fur-
thermore, the
para
-substitution pattern effectively blocks competing reactions with the
aryl ring
- system. Hence,
129
readily undergoes benzylic insertion with 4-bromophenyl
diazoacetate
106
to form product
130
in 69% yield and 83% ee [229]. Insertion into
benzylic methylene sites also occurs readily, but with somewhat attenuated enantiose-
lectivity as well as low to moderate diastereoselectivity [228]. Furthermore, indanes and
tetrahydronaphthalene systems are effective substrates for this chemistry [228,229].
π
MeO
MeO
p
-(Br)Ph
CO
2
Me
Rh
2
(
S
-DOSP)
4
A
r
N
2
2,2-DMB, 0°C
CO
2
Me
1
0
6
1
2
9
69% yield
83% ee
1
3
0
Scheme 4.33.
Benzylic C -H insertion into
129
.
The synthetic potential of this reaction was shown in the syntheses of (+)-imperanene
(
54
) and (
) - conidendrin (
134
) [229], where benzylic C-H activation of
132
with vinyl-
diazoacetate
131
produced both enantiomers of
133
depending on which enantiomer of
the catalyst was employed [229]. Rh
2
(
R
- DOSP)
4
produced the
S
- enantiomer
133
in 43%
yield and 91% ee, whereas Rh
2
(
S
- DOSP)
4
gave
ent
- 133
in 44% yield and 92% ee. The
former was further transformed into (+)-imperanene, whereas the latter was reduced
and deprotected to form (
−
)-conidendrin in 87% yield. Despite the high electron density
of the aryl rings involved, no competing cyclopropanation was observed [229] (Scheme
4.34 ).
−
