Chemistry Reference
In-Depth Information
CO
2
Me
MeO
2
C
Grubbs II
OSiEt
3
OSiEt
3
8.440
8.441
Scheme 8.118
Me
Me
O
O
O
O
Grubbs
I
I
8.442
8.443
Scheme 8.119
In a synthesis of the guanacastepene skeleton (Scheme 8.118), two methyl groups were attached to the
“undesired” alkene to ensure that ene-yne-ene metathesis proceeded as desired.
130
Electronic control may also be used. If there is a choice between a simple alkene and an electron-poor
alkene, the reaction will initiate at the simple alkene (Scheme 8.119).
131
8.3.9 Tandem Reactions
Alkene metathesis chemistry is ideally suited for tandem processes by designing substrates with multiple
alkenes. This example includes ring opening, ring closing and cross-metathesis (Scheme 8.120).
A sequence involving a ROM featured as part of a synthesis of deoxypukalide
8.455
, a cembranoid from
a Pacific octocoral (Scheme 8.121).
132
The starting material was prepared by carboalumination of butynol
8.446
, followed by an iodine quench. After oxidation to the aldehyde, a second alkene was added as a
Grignard reagent, and the alcohol
8.448
was converted to an ester
8.450
with a mixed anhydride
8.449
of
cyclobutene carboxylic acid. Treatment of the ester
8.450
with methallyl alcohol and the Grubbs second-
generation catalyst resulted in a tandem process consisting of an RCM, forming the butenolide, and ROM,
opening the cyclobutene, and a cross-metathesis with the methallyl alcohol, giving the lactone
8.451
.The
iodo-substituted alkene played no part in the tandem reaction. The synthesis was completed by a Stille
coupling with the furyl stannane
8.452
to attach the furan moiety, followed by macrocycle formation using
the Hiyama-Nozaki-Kishi reaction and some functional group interconversions.
8.3.10 Metathesis Side Reactions
A surprising result was found during an attempt to carry out a ring-closing metathesis during a synthesis
of 3-deacetoxy-6-deacetylcalicophirin, a marine natural product (Scheme 8.122).
133
When the triene
8.456
H
Et
Grubbs I
Et
H
OTBS
TBSO
8.444
8.445
Scheme 8.120
