Biomedical Engineering Reference
In-Depth Information
O
RuLn
H
MsO
G-I
(10 mol%)
CH
2
Cl
2
, reflux, 3 h
15
O
O
O
O
or
53%, 81% brsm
O
O
O
RuLn
118
14
115
14
14
MsO
MsO
MsO
116
117
F
F
+
LnRu
RuLn
O
G-I
(10 mol%)
CH
2
Cl
2
, reflux, 3 h
then overnight at rt
O
O
H
MsO
15
82%
F
O
O
O
14
119
MsO
O
O
14
14
122
MsO
MsO
120
121
123
SePh
3
OH
H
OH
H
O
O
NaO
CO2Et
OH
H
S
125
O
O
O
O
O
O
O
15
15
O
O
NBoc
O
O
NH
2
G-II
CH
2
Cl
2
, reflux, 16 h
74%
O
15
NBoc
EtO
2
C
126
124
(
+
)-Didemniserinolipid B
PhSe
CO
2
Et
SCHEME 5.31
Relay ring-closing metathesis in the total synthesis of (+)-didemniserinolipid
B by Burke and coworkers.
5.8. TANDEM METATHESIS
The remarkable efficiency and versatility of the metathesis reaction in carbon-carbon
bond constructions has elevated this technology to take on new dimensions. In
particular, the possibility of constructing multiple carbon-carbon bonds through
sequential metathesis reactions in a single reaction vessel should enable a rapid and
operationally simple entry to a high degree of molecular complexity [57,58]. This
concept was first realized by Grubbs and Stille in their total synthesis of sesquiter-
penoid (
(9,12)
-capnellene [59]. In this instance, the Tebbe reagent [60] employed
represented one of the rare examples as metathesis initiator in contrast to the
conventional molybdenum- and ruthenium-based catalysts. Indeed, upon the extru-
sion ofMe
2
AlCl, the so obtained titanium carbene species
128
participates in a [2
รพ
2]-
cycloaddition engaging the olefinic moiety of substrate
127
to generate titanacycle
129
D
)-
. Elevating the reaction temperature from 25 to 90
C triggered the cycloreversion
of
. The latter species
underwent a final intramolecular olefination reaction engaging its carbonyl moiety to
afford [5,5,4]-tricyclic system
129
, leading to the formation of titanium carbene species
130
131
, thereby completing the metathesis cascade. The
sensitive enol ether
131
was transformed to dioxolane
132
(81% overall yield from
t
-
butyl ether
), a key synthetic intermediate that was further elaborated to the
targeted natural product (Scheme 5.32).
Over the years, Philipps and coworkers have synthesized a number of bioactive
natural products based on an ingenious strategy involving tandem olefinmetathesis of
[2,2,2]-bicyclooctene systems as the key reaction [61]. The cyanthiwigins are a family
131
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