Chemistry Reference
In-Depth Information
Grubbs I
Ti(O
i
-Pr)
4
O
TBS
O
O
O
O
OTBS
n
-C
5
H
11
n
-C
5
H
11
8.297
8.298
E
:
Z
= 2.7:1
O
OH
1. KMnO
4
, Ac
2
O
2. aq. HF
O
O
O
n
-C
5
H
11
8.299
Scheme 8.81
tetraisopropoxide was also added. The titanium additive breaks up the unreactive chelate complex by coordi-
nating to the ester oxygen. The metathesis product, obtained as an
E
/
Z
mixture, was oxidized to an
-diketone,
which cyclized to the natural product
8.299
upon deprotection.
Coordination by a sulfur atom of a nearby dithiane was suggested to be the cause of the difficulty
in forming an unsaturated lactone in a synthesis of the anticancer agent EBC-23
8.302
, from the Aus-
tralian rain forest tree
Cinnamomum laubatii
(Scheme 8.82).
97
The ring-closing metathesis reaction of diene
8.300
was ultimately successful using the second-generation Hoveyda-Grubbs catalyst under microwave
conditions.
The reason for the failure of an RCM may not always be obvious, and may be attributed to various factors.
One example is the synthesis of dactylol (Scheme 8.83)
8.309
.
98
The starting material was prepared by
addition of a methyl copper reagent to cyclopentenone
8.303
, and trapping the resulting enolate with an
aldehyde. The aldol product
8.304
was dehydrated and the conjugated alkene
8.305
was selectively reduced.
This reaction was not only regioselective, but also stereoselective, giving the
trans
isomer
8.306
. Addition of
a Grignard reagent gave the diene
8.307
as a separable mixture of isomers. The desired isomer was treated
with Schrock's catalyst, but no product was found. This might be due to either interaction between the alcohol
and the catalyst, or the substrate not having a suitable conformation with the two alkenes in proximity. This
problem was solved by silylation. The silyl ether
8.308
underwent RCM and deprotection gave the natural
product
8.309
.
O
O
TBS
TBS
O
O
O
S
O
HG-II,
μ
w
O
O
O
S
O
S
S
n
-C
13
H
27
n
-C
13
H
27
TBSO
TBSO
8.300
8.301
H
OH
O
1. HF, H
2
O, CH
3
CN
2. (NH
4
)
2
Ce(NO
3
)
6
OH
O
O
O
n
-C
13
H
27
H
8.302
Scheme 8.82
