Chemistry Reference
In-Depth Information
1. Cp
2
ZrCl
2
,
DIBAL
2. I
2
Br
O
MOM
HO
I
HO
Br
TBSO
OTBS
2.139
2.144
1.
(dpephos)PdCl
2
2. Me
2
Zn, (
t
-Bu
3
P)
2
Pd
3. MeOH, K
2
CO
3
BrZn
SiMe
3
Zn
2
(dpephos)PdCl
2
HO
2.140
O
MOM
1. Cp
2
ZrCl
2
, Me
3
Al
2. I
2
HO
I
TBSO
OTBS
2.141
2.145
Zn
2
(dpephos)PdCl
2
1. Cp
2
ZrCl
2
, DIBAL
2. I
2
HO
2.142
O
MOM
1. Cp
2
ZrCl
2
, Me
3
Al
2. I
2
3. TBSCl, C
3
N
2
H
4
I
TBSO
I
TBSO
OTBS
2.146
2.143
1.
t
-BuLi
2. ZnBr
2
(dpephos)PdCl
2
O
MOM
TBSO
TBSO
OTBS
2.147
1. TBAF
2. Dess-Martin
3. NaClO
2
, Na
2
HPO
4
O
MOM
HO
2
C
2.148
TBSO
OTBS
Scheme 2.48
molecules. For instance, the vinyl bromide
2.157
was coupled with an aryl tin reagent with retention of
stereochemistry (Scheme 2.50).
52
The substrate contains an enol ester, an alkene, a ketone and a nitro group.
This tremendous substrate tolerance is very significant for natural-product synthesis. In a synthesis of
rapamycin
2.160
, a double Stille coupling was used to close the macrocycle in the last step after all of the
deprotections had been carried out (Scheme 2.51).
53
Other “no protecting group” Stille couplings are in
syntheses of manumycin
2.163
(Scheme 2.52)
54
and indanomycin (Scheme 2.53).
55
One advantage of organotin reagents is that they can be easily purified by chromatography or distillation.
Another advantage is the number of methods that can be used to make them. Simple organotin reagents are
often made by the reaction of organolithium reagents or Grignard reagents with tin halides (Scheme 2.54).
The reverse, the addition of a tin nucleophile to an organic electrophile, can also be used (Scheme 2.55).
Tin reagents can also be prepared by the addition of tin radicals to multiple bonds (Scheme 2.56). The
palladium-catalysed coupling of organic halides or their equivalent with distannanes is a mild method
