Chemistry Reference
In-Depth Information
could cause an undesired increase of homocoupled
by-products (Ar
1
-Ar
1
); and in the absence of a
common functional group in substrates
d-h
in Fig.
22.15, a solid-phase approach would require the
development of a suitable linking strategy. On the
other hand, it was also pointed out that when a by-
product from the reactant is formed with concomi-
tant detachment of the fluorous unit (Ar
1
-Ar
1
),
simple extractive work-up is not sufficient to sepa-
rate this component from the desired product
(Ar
1
-Ar
2
). This problem probably would not appear
in the polymer-supported solid-phase method,
and the final chromatographic separation could be
avoided.
Because the relatively long reaction time of
the Stille reaction is undesirable for rapid parallel
synthesis applications, Curran and co-workers
have developed a microwave-assisted equivalent of
the original thermal method [104]. A series of
coupling products were synthesised using different
halides and triflates (39-96% yields) and the
reactions required only 90-120 s for completion. The
reaction components were distributed in the tripha-
sic mixture (water-dichloromethane-FC-84) and
Fig. 22.14
Comparison of the reactivity of tributyltin hydride
and the fluorous analogue in (
a
) formylation and
(
b
) cyclisation-formylation reactions.
The Grignard reaction of
F
-hexylethyl magnesium
iodide with phenyltrichlorotin resulted directly in
the phenyl reagent (R
f
6
CH
2
CH
2
)
3
SnPh, whereas
other derivatives (4-methoxyphenyl, 2-furyl, 2-
pyridyl) could be obtained from the tin bromide
intermediate (Fig. 22.10) [103]. The first Stille reac-
tions were carried out under standard conditions
using lithium chloride additive. The efficiency of the
aromatic coupling process was demonstrated by the
parallel syntheses of each tin reactant with four dif-
ferent aryl halogenides and a triflate (Fig. 22.15).
The coupled biaryls were extracted to the organic
layer by the three-phase distribution method and
purified further using preparative thin-layer
chromatography.
The advantages of this liquid-phase combinatorial
process in comparison with the solid-phase equiva-
lent are as follows: the reaction could be conducted
in homogeneous phase; the application of a large
excess of the tin reagents was unnecessary, which
