Biomedical Engineering Reference
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Et
Et
Et
Et
Et
Et
Et
Et
Si
Si
RuLn
Si
O
Si
O
O
O
O
O
O
O
Ph
Ph
Me
Me
G-II
(15 mol%)
PhMe, 90°C, 30 min
Ph
Me
Me
TMSO
TMSO
TMSO
TMSO
RuLn
Me
Me
Ru
Me
Me
Me
Me
Ph
Me
Me
79
80
81
82
Et
OH
Et
O
O
OH
Si
O
Me
Me
Me
Ph
O
H
2
SO
4
, CH
2
O
aq
63%
TBAF, AcOH
THF, 23°C, 10 min
74-79% (2 steps)
HO
HO
HO
Me
Me
Me
Ph
TMSO
Me
Me
OH
Me
Me
Me
Me
84
83
(−
)-Irofulven
(−
)-Acylfulvene
SCHEME 5.23
Silicon-tethered ring-closing metathesis
in the total
synthesis of
(
)-irofulven and (
)-acylfulvene by Movassaghi et al.
PivO
PivO
HO
O
G-II
(10 mol%)
1,2-Dichloroethane
80-90°C, 3 h
then TBAF
THF, reflux, 4-5 h
61% (2 steps)
EtO
2
C
H
OEt
O
OEt
HO
TBSO
H
O
Si
O
EtO
O
EtO
OH
O
TBSO
TBSO
H
OAc
H
H
S
S
HO
(
−
S
S
85
86
87
)-Cochleamycin A
SCHEME 5.24
Silicon-tethered ring-closing metathesis
in the total
synthesis of
(
)-cochleamycin A by Lee and Mukherjee.
enabled the preparation of hydroxy
, a late-stage intermediate
reported in the total synthesis of (-)-cochleamycin A by Roush and Dineen
(Scheme 5.24) [47].
A suitably chosen tether not only improves the efficiency and selectivity of the
carbon-carbon bond forming process, but depending on the nature of the tether,
additional functionalities could also be incorporated, thereby offering extra synthetic
utility. In this context, an example was illustrated by Cossy and coworkers in their
synthesis of an analogue of the originally assigned structure of the antihelminthic and
antitumor agent (
b
-ketoester
87
)-mycothiazole [48]. In this instance, a sulfonate tether was
employed that enabled the preparation of unsaturated sultone
90
from allyl sulfonate
89
)
under the influence of Grubbs second generation catalyst. To introduce the (
Z
)-dienol
functionality required in the targeted natural product, amethodology developed by the
Cossy group was put into practice. Thus, sequential alkylation of sultone
via ring-closing olefinmetathesis in 70%yield (over the two steps from alcohol
88
with 1,1-
dimethoxy-3-iodopropane (LiHMDS, 76%yield) and carbenoid ICH
2
MgCl led to the
generation of a transient species
90
91
, which underwent facile
b
-elimination and
extrusion of sulfur dioxide to give (
Z
)-dienol
92
in 60% yield. Further elaboration
of the dimethyl acetal terminus of (
Z
)-dienol
92
led to the successful completion of an
analogue (
)-mycothiazole (Scheme 5.25).
Application of the tethered metathesis strategy is not limited to medium-sized
rings. Indeed, when the metathesis reaction simply serves its role in the carbon-
carbon bond construction where the isomeric purity of the newly formed olefin is
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