Biomedical Engineering Reference
In-Depth Information
R
3
R
3
O
OSiR
3
R
3
O
5-exo
R
1
R
2
R
2
6-
endo
R
1
R
1
R
2
1,6-enyne
R
3
R
3
R
2
R
1
O
R
3
R
2
R
1
R
2
5-
exo
6-
endo
R
1
R
3
SiO
O
1,5-Enyne
SCHEME 4.47
exemplified by the 5-
exo
or 6-
endo
addition of silylenol ethers to alkynes shown
in Scheme 4.47.
Several total syntheses of natural products based on the use of this highly
valuable transformation have been described. For instance, Toste and coworkers
reported the total synthesis of the alkaloid (
, in which a 5-
endo
cyclization of a silylenol ether-iodoalkyne was employed [45]. Hence, treatment of
substrate
þ
)-lycopladine A
169
with 10mol% of (Ph
3
P)AuBF
4
in a mixture of CH
2
Cl
2
and methanol
induced the nucleophilic addition of the silylenol ether on the iodoalkyne. This
resulted in the efficient formation of the
b
,
g
-unsaturated bicyclic ketone
167
(95%
yield) after a final protodemetalation step (Scheme 4.48). Notably, the quaternary
center at the ring junction, which is a key architectural feature of the targetedmolecule,
was easily and efficiently introduced. The compatibility of the gold-catalyzed
transformation with the iodine atom at the terminus of the alkyne in substrate
168
167
168
is also of high interest since the resulting vinyl iodide functionality in
could be
used in a subsequent palladium-catalyzed Suzuki-Miyaura coupling reaction.
Avery similar approach has been used by the same authors for the synthesis of
the alkaloid (
þ
)-fawcettimine
170
(Scheme 4.49) [46].
Another application of this subclass of cycloisomerization was reported
by Nicolaou and coworkers in their synthesis of the antibiotic (
)-platencin
173
(Scheme 4.50) [47]. A part of the tricyclic enone
172
core of the natural product
OBn
(Ph
3
P)AuCl (10 mol%)
AgBF
4
(10 mol%)
CH
2
Cl
2
/MeOH (10:1)
40°C, 3 h
95%
TBSO
OBn
TBS
O
I
I
+ MeOH
AuL
- TBSOMe
[Au]
H
H
167
OBn
NMe
2
OBn
OH
[Pd(PPh
3
)
4
] (5 mol%)
NMe
2
O
O
O
BPin
I
2 steps
NaOMe
MeOH/benzene
83%
N
H
H
H
(+)-Lycopladine A
169
168
SCHEME 4.48
Synthesis of (
þ
)-lycopladine A by Toste and coworkers.
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