Formation of new C-O and C-N bonds via base promoted Csp2-Csp3 bond cleavage of α-nitro ketone

Article abstract of DOI:10.1016/j.tetlet.2015.11.002

A catalyst free protocol has been developed for nucleophilic _C^sp2_-C^sp3 bond cleavage of α-nitroketone in the presence of potassium carbonate to create new C-O and C-N bonds. A series of different substituted α-nitroketones could be selectively cleaved and converted into corresponding esters and tosylamides in the presence of alcohols and bromamine-T, respectively.

Full text of DOI:10.1016/j.tetlet.2015.11.002

Tetrahedron Letters 56 (2015) 7008–7011
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Formation of new C–O and C–N bonds via base promoted Csp2–Csp3
bond cleavage of a-nitro ketone
⇑
Manas Jyoti Sarma, Arun Jyoti Borah, Kamal Krishna Rajbongshi, Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati 781 014, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A catalyst free protocol has been developed for nucleophilic Csp2 —Csp3 bond cleavage of
the presence of potassium carbonate to create new C–O and C–N bonds. A series of different substituted
-nitroketones could be selectively cleaved and converted into corresponding esters and tosylamides in
the presence of alcohols and bromamine-T, respectively.
a-nitroketone in
Received 21 September 2015
Revised 28 October 2015
Accepted 1 November 2015
Available online 2 November 2015
a
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
C–C cleavage
a-Nitroketone
Bromamine-T
Esters
Amide
Introduction
has been reported by Paine and coworkers for the synthesis
of corresponding acids.3d
similar cleavage of aryl
-hydroxyketones has also been demonstrated by Jiang and
A
Formation of a new C–C or C–X bond via C–C bond cleavage is
receiving considerable attention in modern synthetic organic
chemistry.1 Cleavage of C–C bonds is a highly challenging task
because of their inherent inert nature. The sequential cleavage
and formation of C–X bonds facilitates reorganization of an organic
skeleton which can provide an alternating pathway to construct
new organic structures. In the recent past, a variety of methods
have been developed for oxidative cleavage of C–C bond using
different catalysts based on transition metals such as Cu, Ir, Rh,
Pd, Pt etc.1c,d,f,2 However, the use of expensive and toxic metals
in combination with oxidants limits the application of such
protocols to a greater extent. In this context, the development of
a transition metal-free protocol to achieve C–C bond cleavage is a
superior alternative for various synthetic manipulations.3 Exten-
a
co-workers using K2CO3 and [18]-crown-6 in oxygen atmosphere
to produce corresponding esters.3e
a
-Nitroketones are very important starting material for various
important organic transformations.4 Wang and co-workers
reported an approach to synthesize stable enols from -nitroke-
tone.4g Yan and coworkers, in 2011, reported an asymmetric
protocol for the synthesis of b, -unsaturated -ketones from
Michael addition products of
-nitroketones were successfully synthesized by Menéndez and
a
c
a
a
a
-nitroketones.4a
Again
co-workers4f Xueshun and co-workers reported iron catalyzed
one pot synthesis of oxazoles from
communication, we are reporting a novel transition-metal-free
protocol for Csp2 —Csp3 bond cleavage of -nitroketone to form
a
-nitroketones.4d In this
a
sive studies have been undertaken for the cleavage of C(CO)–C(
a
)
esters and amides (Scheme 1). It is noteworthy that esters and
bond of ketones to synthesize various functionalities such as
acids,2d,3a esters,2h,3b and amides.2a,e,g Recently, Bi and coworkers
reported a method for the conversion of methyl ketones to
aldehydes via copper catalyzed C(CO)–C(methyl) bond cleavage.2i
Another method for oxidative cleavage of C(CO)–C(alkyl) bond
has been developed by Jiao to transform aryl ketones to
corresponding amides in the presence of CuCl2 and TEMPO.2j
amides are widely used in industry and synthetic chemistry and
important structural motif in
a myriad of compounds of
biological and pharmaceutical interest.5 So the development of
an alternative methodology to prepare such compounds always
remains a common practice to the chemist.
Initially, the protocol for C–C bond cleavage was examined for
benzoylnitromethane using methanol in the presence of different
bases to synthesize methyl benzoate (Table 1). In a typical reaction,
benzoylnitromethane (1 mmol) and K2CO3 (3 equiv) was stirred in
methanol at room temperature. After 24 h of reaction at room
temperature, methyl benzoate was isolated in 20% yield. When
Enzymatic cleavage of Csp2 —Csp3 bond of aryl
a-hydroxyketones
⇑
Corresponding author.
E-mail address: pphukan@yahoo.com (P. Phukan).
http://dx.doi.org/10.1016/j.tetlet.2015.11.002
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

M. J. Sarma et al. / Tetrahedron Letters 56 (2015) 7008–7011
7009
O
O
O
O
O
R
K2CO3
MeOH
TsNBrNa
K2CO3
EtOAc
NO2
NO2
R
OMe
R
NHTs
OMe
K2CO3
Heat
+
MeOH
Cl
Cl
Scheme 1. Formation of C–O and C–N bonds via C–C cleavage of a-nitroketone.
Scheme 2. Cleavage of
a-substituted a-nitroketone.
esters in high yield (70–90%). The nature and position of the
substituents on the aromatic ring could not influence the product
yield significantly. However, unsubstituted structures and
p-substituted aromatics were found to produce slightly better yield
(Table 2, 2a–2d). The protocol exhibits good functional group toler-
ance. Aliphatic nitroketones were found to produce comparatively
lower yield of the corresponding esters (Table 2, 2i and 2j).
Table 1
Optimization of methyl esterification processa
O
O
NO2
OMe
K2CO3
Heat
+
MeOH
The method has also been examined for C(CO)–C(
a) bond cleav-
Sl. No.
Base (mmol)
Temp (°C)
Time (h)
Yieldb
age of a nitroketone with -substitution. When 1-(4-chlorophe-
a
1
2
3
4
5
6
7
8
K2CO3(3 mmol)
K2CO3 (3 mmol)
K2CO3 (3 mmol)
K2CO3 (3 mmol)
K2CO3 (2 mmol)
K2CO3 (4 mmol)
Na2CO3 (3 mmol
Cs2CO3 (3 mmol)
rt
24
3
2
2
2
2
2
2
20
78
90
75
60
89
72
68
nyl)-2-nitropropan-1-one was treated with K2CO3 in methanol
under the same reaction conditions, the corresponding methyl
ester was formed in 60% yield after 2 h of reaction (Scheme 2).
A probable mechanistic pathway to explain the C–C bond
cleavage process is depicted in Scheme 3. It is well known that
60
80
100
80
80
80
80
a
-nitroketone prefers to stay as enol and form b-hydroxy
nitroolefin4i,6 where the enolic hydrogen is stabilized by
intramolecular hydrogen bond. Addition of potassium carbonate
enhances the possibility of formation of the enol. Moreover, the
addition of the base led to the deprotonation of methanol leading
to the formation of methoxide ion which undergoes 1,4-addition
to b-hydroxy nitro-olefin. Subsequent protonation-deprotonation
steps, followed by nitromethane elimination, result in the
formation of ester.
a
Reaction condition: benzoylnitromethane (1 mmol), methanol (2 mL).
Isolated yield.
b
the reaction was examined at high temperatures in a Schlenk tube
under nitrogen atmosphere, gratifyingly, we could isolate a high
yield of the desired product within a very short reaction time
(Table 1, entry 2–4). Performing the reaction at different tempera-
tures, the best yield of 90% of methyl benzoate was obtained for
the reaction at 80 °C within 2 h (Table 1, entry 3). Further experi-
ments using different bases such as Na2CO3 and Cs2CO3 could not
produce better results. Finally the use of 3 equiv of K2CO3 as base
and the reaction temperature of 80 °C was considered to be the
optimum conditions for further investigation.
After getting success in the synthesis of esters via C–C bond
cleavage of a-nitroketones, we intended to explore the possibility
of formation of amides using the same strategy. In a trial reaction
of benzoylnitromethane with aniline as the nitrogen-source under
the optimized reaction condition, the C–C bond cleavage was found
to be unsuccessful (Table 3, entry 1). Even in the presence of a sol-
vent, such as ethyl acetate, the reaction was found to be inert
(Table 3, entry 2). We also looked for the possibility of stronger
bases such as NaH and tBuOK, so that deprotonation of aniline
could be facilitated. However, this modification of reaction condi-
tion could not yield fruitful results. Use of other amine sources
such as banzamide and sulfonamide could not drive the reaction
forward. As explained in the mechanism of the esterification
process, the nucleophilicity of the N-source should be the driving
factor to synthesize the desired amidation product. Hence, we
looked for other possibilities such as N-sodio-N-halo amides which
are found to be an excellent amine source.7 An initial attempt using
chloramines-TÁ3H2O could produce the desired sulfonamide in 44%
yield. However, significant enhancement of the yield was observed
when bromamine-T was used as the nitrogen source in ethyl
acetate as solvent at 80 °C (Table 3, entry 8). Use of other solvents
such as dichloromethane and acetonitrile produced diminishing
results.
Having the optimized conditions in hand, the method was
extended to a variety of nitroketones. Results are summarized in
Table 2. Both aromatic and aliphatic structures are compatible
under the present reaction conditions to provide the corresponding
Table 2
Methyl esterification reactions via C–C cleavage of
a
-nitroketonesa
O
O
NO2
OR1
K2CO3
Heat
R1OH
+
1
2
R
R
O
O
O
O
O
O
O
O2N
Br
2a, 90%
2b, 84%
2c, 82%
O
O
O
O
O2N
O
MeO
Br
H
2f, 74%
2d, 85%
Oδ−
N
H
2e, 80%
O
O
O
N
O
MeO
O
O
NO2
O
O
O
H
OMe
OMe
MeO
MeO
O
O
O
B
A
2i, 73%
2g, 77%
2h, 80%
H
Oδ−
N
O
O
O
MeO
Heat
O
O
OH
N
O
N
OMe
+
2j,70%
O
O
C
a
Reaction condition:
a-nitroketones (1 mmol), K2CO3 (3 mmol), methanol
(2 mL), 80 °C, 2 h, Isolated yield.
Scheme 3. Proposed reaction mechanism for esterification reaction.

7010
M. J. Sarma et al. / Tetrahedron Letters 56 (2015) 7008–7011
Table 3
effect of the electronic nature of the substituents on the aromatic
ring of nitroketones is not apparent, however the ortho-
substitution provided lower yield (Table 4, 4h and 4i).
Optimization reaction of amidation processa
O
O
NO2
Conclusions
NHR
K2CO3
Heat
RNH2
+
In conclusion, we have developed a novel transition-metal-free
protocol for C(CO)–C(a) bond cleavage of a-nitroketones leading to
the formation of esters and amides. This nucleophile-assisted pro-
tocol exhibits advantages in terms of operational simplicity, func-
tional group tolerance and the absence of metal catalyst. Using two
different types of nucleophiles such as alcohols and bromamine-T,
Sl. No.
1
Substrate
Base
Solvent
—
Yieldb
—
NH2
K2CO3
3a
2
3
4
3a
3a
3a
O
K2CO3
NaH
EtOAc
EtOAc
EtOAc
—
—
—
a
-nitroketone could be transformed to the corresponding esters
and amides, respectively, in high yield within a short span of time.
tBuOK
5
6
K2CO3
K2CO3
EtOAc
EtOAc
—
—
3bNH
O
S
2
Acknowledgment
Financial support from the Department of Science and
Technology (DST), India (Grant No. SR/S1/OC-43/2011) is gratefully
acknowledged.
NH2
O
3c
O
S
Cl
N
Supplementary data
7
8
K2CO3
EtOAc
EtOAc
44
O
Na
3d
O
S
O
3e
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.11.
002.
Br
N
K2CO3
83
Na
9
10
3e
3e
K2CO3
K2CO3
DCM
MeCN
40
45
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O
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