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temperature, solvent, precatalyst, base and time are thus a careful balance
between ensuring the slowest hydrolysis in combination with the fastest
turnover. Further mechanistic investigations on the hydrolysis of R-BF
3
K
salts under SM coupling conditions was undertaken to elucidate these ob-
servations so greater control and predictability can be made for future
optimizations. Mechanistically, an acid catalysed pathway was shown to give
the most rapid rates of hydrolysis to the corresponding boronic acids. The
basic conditions of SM coupling largely suppressed this pathway. Under
these regular coupling conditions, THF / water 10:1, 3 equiv. Cs
2
CO
3
,a
biphase exists with a very basic minor aqueous phase and an organic bulk
phase, Figure 8.4. Access to the acid catalysed pathway was thus found to be
dependent on the eciency of mixing of the phases. Conditions that in-
duced good mixing, such as the vessel shape, stirring rate, ultrasound etc.,
led to a disabling of the acid-catalysed hydrolysis and a slow background
uncatalysed pathway was observed to occur. Systems that engendered poor
phase mixing led to rapid rates of hydrolysis through the acid catalysed
pathway. Then the release rate of boronic acid was directly correlated to the
side-products formed, i.e., slow hydrolysis from ecient mixing led to a low
concentration of boronic acid and less side-product formation.
Rates of hydrolysis were measured for a range of R-BF
3
K salts and
were found to span five orders of magnitude. This variation was found to
correlate with the DFT-derived B-F bond length of the intermediate
difluoroborane [r(B--F)], as it was sensitive to the structural characteristics
that dominate hydrolysis rates. Thus a reliable parameter was found to
predict relative hydrolysis rates and therefore the eciency of a particular
cross-coupling reaction. In addition, the more easily sourced Swain-Lupton
resonance value for R, behaving as a para substituent in an aromatic ring, in
combination with its weighted Charton steric parameter, correlated well
with rates of hydrolysis (logk
rel
pR
SL
- 0.09n) and thus gave a rapid and
simple tool for their prediction.
Organotrifluoroborates that are very electron rich, e.g. cyclopropyl and
4-methoxyphenyl, undergo very rapid in situ hydrolysis. Hydrolysis is so
HF
KHF
2
Δ
r
(B-F)
Acid catalysed
2 H
2
O
F
RBF
3
K
RB
RB(OH)
2
F
Uncatalysed
major phase
KF
minor phase
Base
Figure 8.4 Hydrolysis of trifluoroborates to boronic acids, indicating the mech-
anisms of the acid catalysed and uncatalysed pathways. The acid cata-
lysed pathway is attenuated when there is e
cient mixing with the basic
minor biphase
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