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NMe
O
O
MeN
K
<< 1
K
<< 1
R
B
150 °C
O
O
O
BO
O
BO
O
R
O
R
O
MeN
NMe
O
O
MeN
K
> 1
K
> 1
R
B
60 °C
BO
O
BO
O
R
R
MeN
Scheme 8.16 Conformational rigidity in MIDA boronates, as determined by vari-
able-temperature
1
H NMR spectroscopy.
MeN
O
t
-Bu
Pd(OAc)
2
, SPhos, K
3
PO
4
O
O
B
O
O
O
dioxane:water (5:1), 60 °C, 6 hr
O
t
-Bu
94% isolated yield
Cl
Scheme 8.17
SM coupling of a heteroaryl MIDA boronate under ''slow-release''
conditions.
with relative ease. They do have a few susceptibilities, however. These include
protic or alcoholic solvents, in which they undergo slow solvolysis to liberate
the boronic acid, although they are generally compatible with aqueous ex-
tractions employing water, brine, aqueous acid, e.g. NH
4
Cl
(aq)
, and even sat-
urated NaHCO
3(aq)
in the absence of alcoholic solvents. They are not stable
towards hard nucleophiles such as LiAlH
4
, DIBAL, TBAF or metal alkoxides.
83
However, they are resistant to Swern, Dess-Martin and Jones oxidations,
83
and
also iodination, Evans aldol and reductive amination reactions, Horner-
Wadsworth-Evans and Takai olefinations and mild reducing agents. They are
also stable towards Stille, Heck, Negishi and Sonogashira couplings, Grubbs
metathesis and Miyaura borylation reactions.
78
In a seminal publication, Burke and co-workers
84
showed that under op-
timized hydrolytic SM coupling conditions, MIDA boronates slowly liberate
boronic acids, analogous to that occurring with organotrifluoroborates
(see above), ensuring that the boronic acid concentration is maintained low
enough to avoid extensive competitive side reactions, such as proto-
deboronation, without this impacting on the rate of productive cross-
coupling (Scheme 8.17). This slow-release strategy was demonstrated for a
number of unstable (vinyl, cyclopropyl, heteroaryl) boronic acids, with
excellent yields (76-99%) of the cross-coupled product, obtained solely
by keeping the boronic acid at low concentration. Under ''fast-release''
conditions, 2-furyl MIDA boronate underwent coupling with comparable
yield to the corresponding freshly prepared 2-furylboronic acid (68% versus
59%). Replication of the ''slow-release'' conditions, by syringe pump
addition of 2-furylboronic acid over 3 h, restored the yield (94%) of the
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