Chemistry Reference
In-Depth Information
OAc
R
CO
2
Me
R = Ph
4-(OMe)Ph
4-(Br)Ph
3,4-Cl
2
Ph
2-Nap
Me
Boc
Rh
2
(
S
-DOSP)
4
17
0
2,2-DMB, r.t.
Boc
R
CO
2
Me
45-65% yield
98-99% ee
N
2
171
152
Scheme 4.49.
Synthesis of 4 - substituted indoles.
elimination sequence with various substituted arylvinyldiazoacetates to form 4-substi-
tuted indoles
171
in 45-65% yield and in 98-99% ee. These examples are particularly
interesting since the 4-position of indoles is diffi cult to functionalize selectively by tra-
ditional means [237] .
The combined C-H activation/Cope rearrangement has found several applications
in natural product synthesis [239,240]. The remarkably high stereoselectivity makes the
transformation an attractive tool in synthesis. A general strategy for the synthesis of a
family of marine diterpenes from
Pseudopterogorgia elisabethae
was developed based
on the combined C-H activation/Cope rearrangement with appropriately substituted
dihydronaphthalenes [239,240]. The reaction between vinyldiazoacetate
173
and racemic
172
(Scheme 4.50) catalyzed by Rh
2
(
R
- DOSP)
4
yielded a 1:1 mixture of the correspond-
ing cyclopropane and the desired C-H activation/Cope rearrangement product [240].
The mixture was, however, inseparable and was consequently subjected to hydrogena-
tion and reduction to yield alcohol
174
in 31% yield (62% in theory) over the three steps
in 90% ee. This intermediate was then used to synthesize (+)-erogorgiaene (
175
) [240] .
The same methodology was used with highly functionalized substrate
176
, which yielded
alcohol
177
in 34% yield (68%) with >95% ee [239]. This intermediate was used in the
syntheses of natural products (− ) - colombiasin A (
178
) and (− ) - elisapterosin B (
179
)
[239]. Also, (+)-elisabethadione and a related
p
- benzoquinone natural product were
synthesized by this approach [239]. The ability of the combined C- H activation/Cope
rearrangement to install the three core stereocenters formed in the reaction with full
relative and absolute stereocontrol, makes this approach very attractive. This has been
a major problem in previous total syntheses of this class of natural products. These
examples constitute some of the most impressive applications of the combined C- H
activation/Cope rearrangement to date [14,239,240] .
Reactions of allyl silyl ethers with vinyldiazoacetates typically give mixtures of direct
C-H activation (
181
, Scheme 4.51) and the combined C-H activation/Cope rearrange-
ment products (
182
) [241]. Heating or microwave conditions converted the formal C- H
insertion products into the desired rearranged products. When R and R′ are alkyl
groups, the combined C-H activation/siloxy-Cope rearrangement product is formed
preferentially. This reaction was demonstrated with several protected allyl silyl ethers,
and furthermore, other diastereomeric products were accessible via the
cis
- allyl silyl
ether series [241] .
The combined C-H activation/Cope rearrangement produces products that are clas-
sically derived from a tandem Claisen/Cope rearrangement. This is a conceptually attrac-
