Chemistry Reference
In-Depth Information
Molander and co-workers
64
demonstrated that systems in which
the amide is further removed from the boryl substituent also undergo
Suzuki-Miyaura couplings with high enantiospecficity [eqn (11.22)]. Using
chiral, enantiomerically enriched b-boryl amides (90) under conditions
similar to those used by Suginome's group, Molander and co-workers
showed that this reaction also proceeds with inversion of configuration.
Highlighting the importance of the amide group, when this substituent was
replaced with an ester, no reaction was observed. Importantly, the starting
materials are readily available in enantiomerically pure form by hydro-
boration of the corresponding alkene using conditions developed by Takacs
and co-workers
28,65
or alternatively NHC
66
or Cu-cat borylations
67
(Scheme 11.10).
MeO
MeO
O
CH
3
BF
3
K
O
CH
3
Ar
ArCl
,Pd(OAc)
2
XPhos, K
2
CO
3
CPME/H
2
O, 95°C
H
H
(11
:
22)
90
91
95% enantiospecificity
inversion
O
O
BPin
O
e
nantioselective
Rh-cat
R'
R'
R'
R
2
N
R
2
N
R
2
N
borylation
hydroboration
92
93
94
Scheme 11.10
Synthetic methods for the preparation of b-borylated amides.
Taking advantage of the protecting features of Suginome and co-workers'
dansyl group (1,8-diaminonaphthalene, dan),
68
Hall and co-workers syn-
thesized chiral bis-boronate 95 and demonstrated the enantiospecific
coupling of one geminal boronic ester chemoselectively in the presence of
the other (Scheme 11.11).
69
As in other amide-directed methods, the reaction
proceeds with inversion of stereochemistry and virtually perfect enantio-
specificity was observed. After removal of the dan group and conversion to
an amide, the remaining boron group was coupled with a second aryl halide,
also stereospecifically (Scheme 11.11).
69
Interestingly, an ester is suciently
activating in the case of the geminal diboron compound 95, but once the
first Suzuki-Miyaura coupling has been performed, this group must be
converted to amide 99 prior to the final coupling. This higher activity of
geminal diboron species 95 is consistent with the work of Shibata and co-
workers, which showed that racemic geminal bis-boron compounds such as
101 react without any directing or activating groups [eqn (11.23)].
70
Consistent with the importance of the second boron substituent, Shibata
and co-workers showed that compounds with simple aliphatic C-B bonds do
not couple under these conditions and furthermore that a silicon substitu-
ent is not able to activate a geminal C-B bond for coupling.
70
Subsequently,
Morken and co-workers demonstrated that this reaction can be carried out
with enantiotopic group selection,
leading to chiral enantiomerically
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