Angewandte
Communications
Chemie
Table 1: Optimization of the cyanation of boron enolates prepared by the
[
a]
1
,4-hydroboration of chalcone.
[
b]
Entry
H-B
Solvent
T [8C]
Yield [%]
2
a
2a’
1
2
3
4
5
6
7
8
9-BBN
HBCy2
HBcat
9-BBN
9-BBN
9-BBN
9-BBN
9-BBN
9-BBN
THF
THF
THF
RT
RT
RT
RT
RT
RT
RT
40
40
84
8
0
75
58
42
26
90
7
0
Scheme 2. Plausible reaction pathway.
17
10
24
45
14
<5
<5
Et O
2
toluene
product 2’ would be generated by the minor pathway. In
contrast to the intermediate 3, the formation of 3’, the boron
center of which is coordinated by the carbonyl group, did not
induce the elimination of the amide moiety. Thus 3’ undergoes
isomerization to give the highly stable product 2’. Indeed,
isolated boron complex 2a’ was not converted into the 2a
when exposed to the above reaction conditions (408C in
THF), thus indicating that 2’ is not an intermediate for this
CH Cl2
2
MeCN
THF
THF
[
c]
9
93 (84)
[a] Reaction conditions: 1a (0.5 mmol), borane (0.525 mmol), solvent
1
(
1 mL), NCTS (0.5 mmol), RT. [b] Determined by H NMR analysis of the
crude reaction mixture using 1,1,2,2-tetrachloroethane as an internal
standard. The value within parentheses refers to the yield of the isolated
product. [c] 9-BBN, 1a, NCTS, and THF were added in succession.
[
22]
cyanation.
With the optimized reaction conditions identified
Table 1, entry 9), we next investigated the substrate scope
(
5
0% of 1a was recovered (entry 7). When the reaction
temperature was increased to 408C in THF, the production of
a’ was suppressed, and the yield of 2a was increased to 90%
entry 8). Furthermore, the highest yield of 2a (84% yield)
of the cyanation (Scheme 3). A number of chalcone deriva-
tives bearing a variety of substituents were examined.
Substrates bearing electron-donating and electron-withdraw-
ing groups in the para positions on the phenyl ring at the 2-
position provided the corresponding cyanated products in
high yields (2b–h), although highly electron-deficient sub-
strates with a nitro group gave a relatively low yield (2i). The
effects of methyl substituents on either the ortho or meta
positions were negligible (2j and 2k). This cyanation appears
to be insensitive to electronic and steric effects by aryl
substituents at the 4-position (2l–n). In addition, electron-rich
heteroaromatics such as thiophene and furan moieties are
well tolerated (2o and 2p). In the reaction of an enone
containing two types of conjugated alkene moieties, one in an
s-cis and the other in an s-trans geometry, the s-cis-moiety
predominantly underwent hydroboration, thus leading to the
formation of the cyanated product 2q. In addition, enones
possessing aliphatic substituents at the 2- and 4-positions were
also applicable to this cyanation (2r–x). In those reactions,
steric bulk of the aliphatic substituents at the 2-positions is
crucial for the selectivity between 1,2- and 1,4-hydroboration.
The presence of a bulky tert-butyl group afforded the product
2r in high yield by selective generation of the boron enolate
through 1,4-hydroboration. In contrast, a smaller ethyl group
resulted in a lower yield of the cyanated product because of
the competitive 1,2-hydroboration, and thus the delivery of
2
(
was obtained when all of the reagents were added in
succession, thus demonstrating that the prior in situ prepa-
ration of the boron enolate is not required for this reaction
(
entry 9). In addition, an examination of other electrophilic
cyanogen sources revealed that TsCN was also a suitable
reagent, but cyanogen bromide, thiocyanate, and hypervalent
iodine reagents gave lower yields of 2a.
[22]
Control experiments using the corresponding silyl eno-
late, instead of the boron enolate derived from 1a, failed to
give the cyanated product 2a in both the absence and
presence of a boron Lewis acid. The corresponding lithium
enolate gave 2a but the yield was moderate. These results
clearly show that the use of a boron enolate is crucial for the
success of this conversion. Although details of the reaction
mechanism are not yet clear, we postulate the following
reaction pathway: The reaction is assumed to be triggered by
the sufficient activation of NCTS by the coordination of its
cyano group to the strained and Lewis-acidic boron center of
the 9-BBN-based boron enolate. This coordination would
enhance the nucleophilicity of the boron enolate, thus
[
22]
[23]
promoting the addition to the cyano group of NCTS.
However, no direct evidence for the interaction between
the cyano group and the boron center has been obtained at
[
22]
the corresponding allylic alcohol. To the contrary, steric
effects of aliphatic substituents at the 4-position had negli-
gible effects in this system (2u–x). Notably, the use of a-
substituted enones also proceeded effectively to afford b-
ketonitriles bearing a quaternary a-carbon center (2y and
2z), which would be otherwise difficult to access, although
a certain amount of 1,2-hydroboration products were also
[24]
this stage. After the nucleophilic attack of a boron enolate
to the cyanao group of NCTS, two types of intermediates,
namely, 3 and 3’, would be generated (Scheme 2). When the
intermediate 3, the boron center of which is coordinated by
the sulfonyl group, is generated, the elimination of the amide
moiety occurs, thus leading to the formation of the cyanated
product 2. The Lewis-acidic boron center would also be
expected to play a key role in this elimination step. The
[
22]
formed.
2
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
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