Biomedical Engineering Reference
In-Depth Information
Cl
H
O
H
O
OH
1. (Ph
3
P)AuNTf
2
(5 mol%)
MsOH (1.2 equiv)
CH
2
Cl
2
, 4 Å MS, rt, 1 h
4
HN
HN
3 steps
Cl
OMe
O
2.
H
(8 equiv)
OMe
B
O
OMe
OMe
-40°C, 24 h
OMe
OMe
(dr = 30:1)
3. MeOH, K
2
CO
3
65°C, 4 h
62%
(3 steps)
OMe
O
H
H
OH
O
OH
OMe
MeO
N
O
N
OMe
Ph
3
P, DEAD, toluene
(+)-Subcosine II
166
71%
OMe
OMe
OMe
OMe
SCHEME 4.46
Synthesis of (
þ
)-subcosine II by Zhang and coworkers.
study was different. Piperidinols
165
were formed starting from
N
-homopropargylic
amide
by a one-pot sequence initiated by a gold-catalyzed cycloisomerization.
Hence, treatment of
162
162
with an electrophilic gold complex furnished the cyclic
imidate
163
, which was then chemoselectively reduced to afford
a
-amino ether
164
.
165
after a subsequent reduction step. Following this process, a wide range of substituted
piperidin-4-ols could be synthesized in moderate to excellent yields (47-83%) and
diastereoselectivities (ds = 2:1 to 25:1).
The total synthesis of (
The latter then underwent spontaneous Ferrier rearrangement to finally afford
, which was completed in 22%
overall yield and in six steps starting from 3,4-dimethoxybenzaldehyde, proves the
synthetic utility of this method (Scheme 4.46) [44].
þ
)-subcosine II
166
4.4. GOLD-CATALYZED FORMATION OF CARBOCYCLES
The methods that have been employed for the synthesis of carbocycle-containing
natural products are extremely diverse. They generally involve the initial activation
of an alkyne by an electrophilic gold species and lead to the formation of
cyclic products of variable complexity by the creation of one or several C-C and
C-heteroatom bonds.
4.4.1. Cyclizations Involving the Formation of a Single
New C-C Bond
4.4.1.1. Enol-Yne Cyclizations The gold-catalyzed cycloisomerization of
enynes is a domain of activity that has attracted considerable attention. It can
lead to a great variety of carbocyclic structures in an easy and efficient manner [31].
It also represents a powerful tool for the creation of quaternary stereocenters as
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