Biomedical Engineering Reference
In-Depth Information
Me
Me
Me
Me
M
Me
M
Me
OTBS
OTBS
OTBS
OTBS
172
(3 mol%
)
Pentane
22°C, 6 h
97%
LnMo
LnMo
LnMo
171
173
174
175
i
-Pr
i
-Pr
Ar
N
O
Me
Me
Me
OH
Me
Me
Mo
TBSO
Me
Me
Ph
O
O
Ar
H
H
Me
172
176
(
+
)-Africanol
(ee = 87%)
SCHEME 5.39
Asymmetric ring-opening metathesis reaction in the total synthesis of
(
þ
)-africanol by Hoveyda and coworkers.
hydroazulene system bearing a tertiary alcohol at the ring junction and allowed the
total synthesis of (
)-africanol through further elaboration of the key intermediate
176
(Scheme 5.39) [72].
The first example of a Ru carbenoid-catalyzed enantioselective metathesis
process was demonstrated by Hoveyda and Gillingham in their total synthesis of
(
)-baconipyrone C, a polyketide natural product isolated from
Siphonaria baconi
collected from intertidal rock platforms near Melbourne, Australia. In this instance, in
the presence of chiral ruthenium catalyst
þ
177
underwent asymmetric ring-opening olefin metathesis to generate transient ruthe-
nium carbenoid
178
, [3,2,1]-oxabicyclic system
, which participated in a subsequent olefin cross-metathesis with
styrene to afford tetrahydropyran
179
in 62% yield with 88% ee. Subsequent opening
of the tetrahydropyran moiety within
180
180
under Birch-type reduction conditions
provided alcohol
, an intermediate containing the C2C4 stereotriad required in the
targeted natural product (Scheme 5.40) [73].
In the total synthesis of the aspidosperma alkaloid (
181
)-quebrachamine, Hoveyda,
Schrock, and coworkers illustrated the concept of rational catalyst design, based on
þ
Ph
Ph
MesN
N
I
Ru
O
O
i
-Pr
OPMB
Me
OPMB
Me
Me
OPMB
Me
Me
Ph
Me
178
(2 mol%)
neat,
O
O
Ph
+
−
15°C, 20 h
62%
(8 equiv)
Ph
O
LnRu
177
179
180
(88% ee)
(
E
/
Z
> 98:2)
Na, NH
3
,
t
-BuOH, Et
2
O
−
70%
78°C, 3 mi n
Et
O
Me
Me
Me
Me
O
O
Me
Me
3
Me
4
2
Ph
3
O
O
OH
O
O
4
2
Me
Me
PMBO
OH
Et
Et
181
(
+
)-Baconipyrone C
SCHEME 5.40
Tandem asymmetric ring-opening metathesis/cross-metathesis in the total
synthesis of (
þ
)-baconipyrone C by Hoveyda and Gillingham.
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