Biomedical Engineering Reference
In-Depth Information
G-II
(20 mol%)
O
CH
2
Cl
2
(0.005 M)
O
O
O
O
O
O
O
O
O
LnRu
(10 equiv)
LnRu
45°C, 13 h
83%
139
140
141
(
+
)-8-
epi
-Xanthatin
SCHEME 5.34
Tandem enyne ring-closing metathesis/cross-metathesis in the total synthe-
sis of (
þ
)-8-
epi
-xanthatin by Martin and coworkers.
second generation catalyst led to the generation of an intermediate metal carbene
species
140
, which underwent ring closure to generate a new metal carbene species
141
. Participation of metal carbenoid
141
in olefin cross-metathesis with methyl vinyl
ketone then furnished (
)-8-
epi
-xanthatin with an impressive 83% yield over these
two transformations (Scheme 5.34) [63].
Employing a tandem metathesis reaction as the final step in total synthesis has
been demonstrated by Hatakeyama and coworkers in their endeavor toward
(
þ
þ
)-
b
-erythroidine [64]. In this instance, treatment of diene-yne substrate
142
with
Grubbs first generation catalyst furnished (
-erythroidine, which was accompa-
nied with trace amount (ca. 4%) of the olefin ring-closing metathesis product
þ
)-
b
.
In this case, the outcome of the metathesis reaction was strongly dependent on the
substrate and choice of reaction conditions, as illustrated in the reactions engaging
diene-ynes
143
144
147
150
152
. Furthermore, formation of the tetrahydroindole
moiety was deliberately postponed to the final step of the synthesis due to its extreme
sensitivity under basic conditions, as observed in the unsuccessful functionalization
of tandem metathesis products
,
,
, and
145
and
148
(Scheme 5.35).
H
O
O
O
N
N
N
G-I
(10 mol%)
O
O
O
+
CH
2
Cl
2
, 25°C, 6.5 h
MeO
MeO
42%, 66% brsm
MeO
142
143
(+)-
β
-Erythroidine
α,β
-Unsaturated/
β,γ
-unsaturated: 6/94
MeO
2
C
MeO
2
C
MeO
2
C
12
TBSO
TBSO
TBSO
N
MeO
2
C
N
MeO
2
C
N
N
Conditions
N
Conditions
O
MeO
2
C
O
O
+
N
+
MeO
MeO
MeO
MeO
MeO
MeO
144
145
146
147
148
149
Conditions
145
:
146
:
144
Conditions
148
:
149
:
147
Catalyst
Substrate
12
S
12
R
Catalyst
G-I
(10 mol%)
G-II
(10 mol%)
Reflux, 14 h
Reflux, 1 h
27:0:26
57:15:0
G-I
(20 mol%)
G-II
(20 mol%)
Reflux, 14 h
rt, 4 h
0:27:9
66:0:0
H
MeO
2
C
O
MeO
2
C
O
HO
N
N
HO
N
G-II
(20 mol%
)
O
G-I
(10 mol%)
HO
N
O
HO
CH
2
Cl
2
, rt, 1.5 h
CH
2
Cl
2
, reflux, 12.5 h
MeO
55%
153
:
152
= 7%:55%
MeO
MeO
MeO
150
151
152
153
SCHEME 5.35
Tandem enyne/alkene ring-closing metatheses in the total synthesis of
(
þ
)-
b
-erythroidine by Hatakeyama and coworkers.
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