Chemistry Reference
In-Depth Information
Br
Br
Pd/C, PPh
3
,
n
-Bu
4
NBr, Na
2
CO
3
B(OH)
2
O
I
O
2.130
2.131
2.132
OH
OH
O
Al
Pd(OAc)
2
, PPh
3
,
DMPU
Red-Al
®
RO
OR
O
2.133
2.134
O
OH
Br
ZnCl
2
,
PEPPSI
S
S
O
2.135
Scheme 2.46
Cl
Br
Et
MeO
2
C
ZrCp
2
Et
Cp
2
ZrH
Cl
ZnCl
2
, (Ph
3
P)
4
Pd
MeO
2
C
Et
Et
Et
Et
2.136
2.137
2.138
Scheme 2.47
Thus, sequential Negishi coupling reactions of an alkyne and dimethylzinc delivered the desired stereoisomer
2.145
. Hydrozirconation-iodinolysis of alkyne
2.145
installed an iodide and allowed coupling with the left-
hand fragment
2.143
. After the Negishi coupling of the two fragments, selective deprotection and oxidation
gave the desired carboxylic acid
2.148
with six stereodefined alkenes, which corresponds to mycolactone B.
A Negishi coupling of a vinyl zirconium species
2.150
was one of a series of coupling reactions in syntheses
of
cis
and
trans
bupleurynol
2.156
(Scheme 2.49).
50
The vinyl zirconium species was coupled with a vinyl
bromide
2.153
that was the product of a Negishi coupling of a 1,2-dihaloalkene
2.151
with a diynyl zinc
reagent
2.152
. After desilylation, the syntheses were completed by Sonogashira reactions with either
cis
or
trans
3-iodoallyl alcohol. As the molecule could be brought through the entire sequence without isolation,
the residual palladium from the earlier couplings served to catalyse the final coupling, and no extra needed
to be added.
2.5 Tin: The Stille Reaction
Coupling of organotin reagents is known as Stille coupling.
51
There is now enormous functional-group
tolerance. Tin reagents are stable to many common reagents, as well as water and air. They do tend to be
unstable to strong electrophiles, such as strong acids and halogens, and to some oxidizing agents. The low
reactivity of organotin reagents makes the Stille reaction ideal for the synthesis of highly functionalized
