Biomedical Engineering Reference
In-Depth Information
C
6
H
13
O
RuL
n
O
G-II
(10 mol%)
CH
2
Cl
2
, 40°C
61%
PCy
3
Cl
Cl
NN
O
Ru
C
6
H
13
O
H
C
6
H
13
O
O
O
O
108
109
110
111
112
AcO
OAc
Si
O
OH
C
6
H
13
AcO
OAc
112
C
7
H
15
G-II
(7 mol%)
CH
2
Cl
2
, 40°C
40% (2 steps)
OAc
O
OH
O
C
6
H
13
O
O
OH
114
113
(
−
)-(3
R
,9
R
,10
R
)-Panaxytriol
SCHEME 5.30
Tandem relay ring-closing metathesis/metallotropic [1,3]-shift/cross-
metathesis in the total synthesis of (
)-(3
R
,9
R
,10
R
)-panaxytriol by Lee and Cho.
with alkenyl diacetate
, through the intermediacy of the isolable and catalytically
active ruthenium carbene species
112
111
, to afford ene-diyne
114
in 61% yield accom-
panied with
111
(10%). Ruthenium carbene species
111
could be prepared in 40%
yield by treating
with stoichiometric amount of Grubbs second generation
catalyst. The stability of
108
was presumably due to the low steric pressure of the
alkynyl group and the hydrogen on the carbenic carbon. Alternatively, a silyl ether
relay tether was also employed, as illustrated in substrate
111
. Following an analogous
relay metathesis/metallotropic [1,3]-shift/cross-metathesis cascade sequence, ene-
diyne
113
114
was obtained in 40% yield upon treatment of
113
with Grubbs second
generation catalyst (Scheme 5.30).
In the total synthesis of (
þ
)-didemniserinolipid B, Burke and coworkers
implemented the concept of relay metathesis to address the deficiencies encountered
in their first generation strategy. When olefin metathesis substrate
115
was treated
with Grubbs first generation catalyst,
was obtained in 53% yield, provided the
reaction was terminated prematurely to minimize the formation of by-product
119
.In
this case, two possible ruthenium carbene intermediates could be generated upon
treatment of
118
115
with Grubbs first generation catalyst. While metal carbene species
116
would participate in a productive pathway leading to the desired bicyclic ketal,
117
is likely to undergo oligomerization or other counterproductive pathways.
Furthermore, the styrene by-product plays a detrimental role by contributing to the
formation of by-product
through cross-metathesis. Recognizing these shortfalls,
a revised metathesis precursor
118
was synthesized to ensure site specificity during
the initiation step. In addition, it was anticipated that the stability of the indene by-
product (
120
) in contrast to styrene would disfavor the formation of the cross-
metathesis by-product. Indeed, when metathesis precursor
122
120
was exposed to
Grubbs first generation catalyst, the targeted bicyclic compound
119
was isolated
in a much improved 82% yield. To complete the total synthesis of (
)-didemniser-
inolipid B, the attachment of the ethyl ester side chain required one more metathesis
event between terminal alkene
þ
124
and alkenyl selenide
125
, and the cross-metathesis
product
126
(obtained in 74%yield) was further elaborated to (
þ
)-didemniserinolipid
B (Scheme 5.31) [56].
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