Copper-catalyzed cascade reactions of N-(2-bromoallyl)amines with KHCO 3 as the C1 source: An efficient process for the synthesis of oxazolidin-2-ones

Article abstract of DOI:10.1039/c4ra02304h

A novel synthesis of oxazolidin-2-ones by carbamic acid formation and a subsequent copper-catalyzed intramolecular vinylation from N-(2-bromoallyl) amines and KHCO₃ was developed. KHCO₃ was used as a C1 source and base in this effici

Full text of DOI:10.1039/c4ra02304h

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Copper-catalyzed cascade reactions of N-(2-
bromoallyl)amines with KHCO3 as the C1 source: an
efficient process for the synthesis of oxazolidin-2-
ones†
Cite this: RSC Adv., 2014, 4, 26990
Received 21st March 2014
Accepted 28th April 2014
*
Hongwei Jin, Yukun Yang, Jianhong Jia, Binjie Yue, Bo Lang and Jianquan Weng
DOI: 10.1039/c4ra02304h
www.rsc.org/advances
A novel synthesis of oxazolidin-2-ones by carbamic acid formation and course of our continued research on the copper-catalyzed
a subsequent copper-catalyzed intramolecular vinylation from N-(2- synthesis of heterocycles,8 we unexpectedly discovered a novel
bromoallyl)amines and KHCO3 was developed. KHCO3 was used as a cascade reaction of N-(2-bromoallyl)amine with KHCO3, in
C1 source and base in this efficient and convenient cascade process.
which KHCO3 acted as a C1 source, leading to the formation of
oxazolidin-2-ones in moderate to good yields. The resulting
heterocycles are important ubiquitous substructural units
As an abundant, cheap and nontoxic C1 source for the
production of organic chemicals, carbon dioxide is attractive to
both industrial and academic scientists.1 Extensive research has
been conducted on the transformation of carbon dioxide into
useful bulk products.2 Nevertheless, the critical conditions
regarding the transportation and storage of carbon dioxide as
well as the safety factors associated with high-pressured batch
reaction processes affect its utilization in scientic research and
industrial production to some extent. Meanwhile, as a safe,
cheap and commercially available carbon dioxide equivalent,
inorganic carbonate is rarely used in organic synthesis as a C1
source, and its application is undoubtedly desirable.3
Table 1 Optimization of the reaction conditions for the formation
of 2aa
Entry
Base/equiv.
Ligandb
Solvent
Yieldc (%)
The classical copper-mediated Ullmann coupling reaction
has been developed over one hundred years,4 and great
achievements have been made in the copper-mediated C–N,
C–O and C–C bond formation reactions in the past two
decades.5 Although various ethers and oxygenated heterocycles
can be constructed using a copper-mediated C–O formation
reaction,6 to our knowledge results have rarely been reported on
the copper-mediated vinylation of carboxylic acid.7 During the
1
2
3
4
5
6
7
K2CO3/2.0
K2CO3/2.0
K2CO3/2.0
K2CO3/2.0
Cs2CO3/2.0
KHCO3/2.0
KHCO3/1.0
K2CO3/1.0
KHCO3/2.0
K2CO3/1.0
KHCO3/2.0
K2CO3/0.1
KHCO3/2.0
K2CO3/0.1
KHCO3/2.0
K2CO3/0.1
KHCO3/2.0
K2CO3/0.1
A
B
C
D
C
C
C
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
45
40
48
37
Trace
55
68
8
C
C
C
C
C
DMSO
DMSO
DMF
74
74
60
59
33
9
10
11d
12e
DMSO
DMSO
Scheme 1 The reaction of N-(2-bromoallyl)benzylamine with K2CO3.
a
Reaction conditions: 1a (0.5 mmol), CuI (0.1 mmol), ligand (0.2
mmol), carbonate base (1.0 mmol), and 2 mL of solvent were sealed
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou
310014, P. R. China. E-mail: jqweng@zjut.edu.cn; Fax: +86-0571-88320220
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra02304h
b
in a pressurized process vial at 120 ꢀC for 4 h. Ligand: A ¼ L-proline,
B ¼ N,N-diethylglycine, C ¼ N,N-dimethyl-ethane-1,2-diamine, D ¼
c
d
1,10-phenanthroline. Isolated yield for 2a. The temperature of the
reaction was 110 ꢀC. e The temperature of the reaction was 100 ꢀC.
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which exist in many natural products and biologically active
compounds,9 and can be obtained from CO2 xing reactions.10
Using 0.2 equivalent of CuI as the catalyst and 0.4 equivalent
of L-proline as the ligand, N-(2-bromoallyl)benzylamine (1a) was
treated with 2 equivalents of K2CO3 in DMSO at 120 ꢀC for 2
hours. Aer analyzing the 13C-NMR and IR spectra of the nal
product, we surprisingly found that oxazolidin-2-one A (45%
yield) was obtained instead of the expected aziridine B through
a
direct intramolecular Ullmann-type C–N formation
(Scheme 1).
This unexpected and interesting result prompted us to
screen the reaction conditions (Table 1). Firstly, we set out to
screen the ligands in this reaction, N,N-dimethyl-ethane-1,2-
diamine was found to be the best choice among the ligands
(Table 1, entry 3).
Scheme 2 The proposed mechanism for the formation of 2a.
We then turned our attention to other C1 sources such as
Cs2CO3 and KHCO3. A higher yield was obtained when KHCO3
was used (Table 1, entry 6). To our delight, the yields were
improved when additional K2CO3 was used in the reaction
(Table 1, entries 7 and 8). Finally, we found that the highest
yield of 2a was obtained when a mixture of 2.0 equivalents of
KHCO3 and 0.1 equivalent of K2CO3 was used (Table 1, entry 9).
Varying the solvent from DMSO to DMF did not enhance the
yield of product (Table 1, entry 10). Lower yields were obtained
when the reaction temperature was reduced to 110 ꢀC or 100 ꢀC
(Table 1, entries 11 and 12).
Table 2 Synthesis of various oxazolidin-2-ones 2a
With the optimal conditions established, various N-(2-bro-
moallyl)amines were tested to form the corresponding
oxazolidin-2-ones 2 (Table 2). As shown in Table 2, the products
corresponding to the alkylamine substrates were obtained in
good yields (Table 2 2a–l), and it is noteworthy that even a
strained cyclopropyl substituted amine could give a corre-
sponding ring preserved product 2j. In contrast, the reactions of
arylamines led to lower yields, probably due to the poor nucle-
ophilicity of the arylamines (Table 2 2m and n). However, the
yield could be improved when an electron donating group was
introduced to the benzene ring (Table 2 2o). Importantly, this
process could be extended to the reactions of internal alkenyl
bromides, and modest yields of the products were obtained
under identical reaction conditions (Table 2 2p–r).
According to the previous reports and results above,11
a
proposed mechanism for this oxazolidin-2-one formation
process is described in Scheme 2. When KHCO3 is heated, it
produces CO2 and K2CO3. The substrate 1a reacts with CO2 in
the presence of the base K2CO3 to form the carbamic acid salt X.
The oxidative addition of X with the copper catalyst offers the
intermediate Y. An intramolecular nucleophilic substitution in
Y generates Z. The subsequent reductive elimination in Z
readily affords the nal product 2a and regenerates the copper
species to full the catalytic cycle.
To further demonstrate the applicability and efficiency of
this cascade methodology, a gram-scale reaction was per-
formed. When 1.00 g (4.4 mmol) of 1a was used as the starting
material, the reaction could readily offer 0.60 g of 2a (72%).
Conclusions
In conclusion, we have developed a novel protocol for the
synthesis of oxazolidin-2-ones via a cascade process of carbamic
a
Reaction conditions:
1 (0.5 mmol), CuI (0.1 mmol), DMEDA
(0.2 mmol), KHCO3 (1.0 mmol), K2CO3 (0.05 mmol), and 2 mL of
DMSO were sealed in a pressurized process vial at 120 ꢀC for 4 h.
acid formation and
a
sequential copper-catalyzed
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intramolecular vinylation of carboxylic acid. The utilization of
KHCO3 as the C1 source made this method efficient and
convenient. Further applications of KHCO3 as a C1 source are
being investigated in our laboratory.
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Acknowledgements
This work was supported by the Key Innovation Team of Science
and Technology in Zhejiang Province (2010R50018) and
Chemistry Experiment Demonstration Center of Zhejiang
Province.
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26992 | RSC Adv., 2014, 4, 26990–26992
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