Chemistry Reference
In-Depth Information
An interesting case is the
tert
-butyldimethylsilyl vinyl ether substrate
166
(Scheme
4.47), which readily undergoes the combined C-H activation/Cope rearrangement but
rearranges to the formal C-H insertion product
168
spontaneously [235] . The product
is formed in 78% yield and 95% ee as a single diastereomer. Further treatment with HF
yields product
169
in 84% yield [235]. This type of product is classically generated via
an asymmetric Michael addition to a corresponding
- unsaturated double bond. This
tandem Rh-carbenoid reaction can therefore be considered as a strategic synthetic reac-
tion, which acts as a surrogate for the asymmetric Michael addition (Scheme 4.48) [66].
Product
169
is the product of a Michael addition onto the keto form of 1-naphthol, which
is not a viable sequence. Therefore, the carbenoid approach can be a complementary
method to this classical reaction.
α
,
β
OTBS
Ph
CO
2
Me
Rh
2
(
S
-DOSP)
4
TBSO
166
2,2-DMB, 0°C
CO
2
Me
Ph
167
N
2
160
OTBS
O
Retro-Cope
rearrangement
Ph
Ph
48% HF
84% yield
78% yield
>98% de
95% ee
H
H
169
CO
2
Me
CO
2
Me
168
Scheme
4.47.
Tandem
combined
C - H
activation/Cope
rearrangement — retro - Cope
rearrangement.
O
O
R
Michael
addition
OTBS
R
R
CO
2
Me
Rh
CO
2
Me
CO
2
Me
Scheme 4.48.
The tandem combined C- H activation/Cope rearrangement — retro - Cope rearrange-
ment as a Michael addition equivalent.
By engineering the substrate such that elimination of a substituent generates the
aromatized form of the ring that undergoes reaction, the combined C- H activation/Cope
rearrangement has been expanded to enantioselective syntheses of substituted aromatic
systems [237,238]. Enantioselective synthesis of substituted naphthalenes has been
achieved by this method [238]. A strategic use of this methodology has been demon-
strated in the enantioselective synthesis of 4-substituted indoles (Scheme 4.49) [237].
Substrate
170
readily undergoes the combined C- H activation/Cope rearrangement —
