Chemistry Reference
In-Depth Information
MIDA boronate system, Cu(OAc)
2
in combination with diethanolamine
was found to increase yields substantially and mechanistic studies
indicated that a Cu(DEA)
2
species is probably formed.
C. Boron reagent masking - The ''masking'' of the Lewis acidic boronic
acids in unstable substrates via addition of more Lewis-basic ligands,
e.g. alkoxides, has been shown to improve cross-coupling.
89
Dietha-
nolamine can potentially coordinate to the 2-pyridylboronic acid
following hydrolytic liberation from the MIDA boronate. This inter-
mediate, or one involving acetate, can then undergo transmetallation
with copper, prior to reaction with palladium(II).
D. Slow release - The release of the 2-pyridylboronic acid from the
stable 2-pyridyl MIDA boronate can be tuned to be suciently slow to
stop the boronic acid accumulating, thus reducing the extent of
protodeboronation.
8.4.3 DAN Boronamides
1,8-Diaminonaphthalene (DAN) ligands and related systems have been de-
veloped primarily by Suginome's group
90-92
for iterative cross-coupling (ICC)
and are readily prepared by condensing the free ligand with a boronic acid.
Water is removed azeotropically in refluxing toluene (Scheme 8.20).
93
The DAN-protected boronic acids exhibit particular stability due to elec-
tron donation from the very Lewis-basic nitrogen atoms. This strongly sta-
bilizes the boron centre and the reagent is stable towards aqueous work-up
and column chromatography. In contrast to organotrifluoroborate salts and
MIDA boronates, DAN boronamides are stable towards basic conditions,
which makes them unreactive under all SM coupling conditions. Deprotec-
tion is readily effected under mild acidic conditions (Scheme 8.21). Pre-
sumably protonation of nitrogen is necessary to weaken the B-N bond and
liberate the p-orbital on boron for hydrolytic attack; equilibrium is then
driven to the boronic acid via protonation of the liberated DAN ligand.
Toluene
reflux
NH
2
NH
Ar-B(OH)
2
2 H
2
O
+
B
Ar
+
NH
2
NH
Scheme 8.20 Preparation of DAN boronamides from boronic acids.
[PdP(
t
-Bu)
3
]
2
2 equiv. CsF
Ar'-Br
H
2
SO
4(aq)
or HCl
(aq)
THF, rt
NH
HO
B
Ar
B
Ar
Ar'
Ar
HO
NH
dioxane/water or THF
Scheme 8.21 Deprotection and cross-coupling of aryl DAN boronamides.
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