Chemistry Reference
In-Depth Information
Tf
2
O, py
H
O
N
OTf
2.190
2.191
Me
3
Sn
Pd(PPh
3
)
4
, LiCl
N
2.192
O
2.193
O
O
O
Scheme 2.66
L
Pd
OTf
L
Pd
Cl
LiCl
L
R'
L
R'
Scheme 2.67
2.5.5 Stille Coupling of Triflates
The triflate leaving group was introduced to coupling reactions as an alterative to halogens. They are particu-
larly useful when there is no simple way to prepare the required halide partner. Aryl triflates can be prepared
from phenols and pyridyl triflates can be prepared from pyridones.
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This transformation is usually achieved
using triflic anhydride and an amine base. The coupling of a triflate
2.191,
derived from quinolone
2.190,
with stannane
2.192
was used in a short synthesis of dubamine
2.193
(Scheme 2.66).
The inclusion of lithium chloride is important. This is almost always required when triflates are used. It is
believed that transmetallation is more favourable with a chloropalladium intermediate, generated
in situ
by
ligand exchange, than a palladium triflate (Scheme 2.67).
Vinyl triflates can be prepared from ketones by formation of the enolate, followed by quenching with a
suitable reagent. Triflic anhydride can be used, but triflamide reagents, ArNTf
2
, often give better results.
69
When unsymmetrical ketones are used as the starting material, the use of the kinetic enolate or thermodynamic
enolate can result in the formation of either isomer of the triflate,
2.194
or
2.196
(Scheme 2.68). Each undergoes
coupling without isomerization, giving the two isomers of the diene
2.195
or
2.197
.
2.5.6 Stille Coupling of Alkyl Halides
Stille coupling of alkyl halides with alkenyl stannanes can be achieved using electron-rich alkyl phosphines
ligands, combined with the addition of a fluoride source as a nucleophilic promoter (Scheme 2.69).
70
This
probably works by generating a “stannate” complex
2.201
that participates in transmetallation more readily
than the original stannane, in a similar manner to the addition of Lewis bases to Suzuki reactions (Section 2.6).
2.5.7 Stille Reaction Troubleshooting
There are various occasions when the Stille reaction gives low yields, gives no product or requires unacceptably
harsh reaction conditions. In addition to the use of sophisticated phosphine ligands, various techniques have
been developed to boost rates and yields.
71
One technique is to add a copper salt
72
or silver salt
73
co-catalyst.
Copper(I) iodide is often used. These additives can give a significant rate enhancement (Table 2.2).
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