G Model
CCLET 4492 No. of Pages 3
Chinese Chemical Letters
Communication
A facile transformation of alkynes into
a-amino ketones by an
N-bromosuccinimide-mediated one-pot strategy
a
a
a
Ting Weia, Yongming Zenga,b, , Wei He , Lili Geng , Liang Hong
*
a
Department of Chemistry and Applied Chemistry, Changji University, Changji 831100, China
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China
b
A R T I C L E I N F O
A B S T R A C T
Article history:
A facile transformation of alkynes into
cascade strategy is described. Avariety of a-amino ketones are obtained in moderate to good yields under
mild conditions. To overcome the multi-step synthesis, N-bromosuccinimide is involved in multiple
tasks, playing a key role in the reaction course.
a
-amino ketones by an N-bromosuccinimide-mediated one-pot
Received 8 February 2018
Received in revised form 16 March 2018
Accepted 26 March 2018
Available online xxx
© 2018 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
a-Amino ketones
N-Bromosuccinimide
Alkynes
One-pot synthesis
a-Amino ketones are a class of highly valuable molecules that
substrate scope still remain challenges. Therefore, the develop-
widely exist in natural products and pharmaceuticals [1]. In
particular, they have gained much attention due to their roles as
key intermediates in the syntheses of biologically active com-
pounds [2]. Various approaches have been developed to construct
this class of molecules [3]. All these conventional methods involve
ment of a novel efficient approach for the rapid chemoselective
construction of
a-amino ketones directly from various alkynes is
highly desired. In this context, we wish to report a facile
transformation consisting of N-bromosuccinimide-mediated
one-pot cascade under metal-free conditions (Scheme 1).
the
a
-bromination of ketones [4] or bromohydroxylation of olefins
Phenyl acetylene 1a was selected as the test substrate. The
model reaction of phenyl acetylene 1a with NIS (2.0 equiv.) in H2O
at 80 ꢁC for 1 h, followed by the addition of DBU (3.0 equiv.) and
acetone (1 mL) and stirring at room temperature for 2 h, was
initially examined. 1-(2-Oxo-2-phenylethyl)pyrrolidine-2,5-dione
(2a) was obtained only in 18% yield (Table 1, entry 1). The use of
NCS instead of NIS did not provided the desired product 2a,
whereas with NBS, the yield of 2a reached 71% (Table 1, entries 2,
3), indicating that NBS played a key role in the reaction course. The
effects of various bases were investigated and we found that other
bases, besides DBU, were found to be less effective or even
inefficient (Table 1, entries 3–9). Lower yields were obtained when
the reaction was performed with THF, MeCN, DCM, DMSO, or DMF
as the solvent (Table 1, entries 10–14). To further improve the yield,
the reaction conditions, such as the dosage of DBU, reaction
temperature and time were also optimized. When the reaction
temperature was reduced to 60 ꢁC, the yield significantly decreased
(53%, Table 1, entry 15). Increasing the reaction temperature did
not change the yield (70%, Table 1, entry 16). However, considering
energy consumption, 80 ꢁC was selected as the optimal reaction
temperature. Additionally, a lower conversion was obtained upon
lowering the amount of DBU to 2.0 equiv. (63%, Table 1, entry 17). A
similar yield was achieved in the presence of 3.0 equiv. of DBU
followed by oxidation [5]. Such processes have been frequently
carried out with lachrymatic phenacyl halides [4], toxic bromine
[6] and precious metals [7], which hinder their widespread
applications due to the chemical toxicity and tedious handling
requirements. Recently, halogen-activated organic reactions have
provided an attractive approach to this transformation under
metal-free conditions, especially the halonium-initiated one-pot
cascade [8]. For example, Sudalai reported the direct transforma-
tion of alkenes and enol ethers into a-imido carbonyl compounds
with the combination of N-bromosuccinimide (NBS) and dimethyl
sulfoxide (DMSO) [9]. The Kshirsagar group demonstrated an NBS-
promoted one-pot strategy [10]. Liang and co-workers developed
the method of simultaneous intramolecular C
formation of -amino ketones via halogen activation [11].
However, there have been few reports of the simple and efficient
conversion of alkynes into -amino ketones under metal-free
¼O and CꢀꢀN bond
a
a
conditions [12]. Addressing the regioselectivity and expanding the
* Corresponding author at: Department of Chemistry and Applied Chemistry,
Changji University, Changji 831100, China.
1001-8417/© 2018 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: T. Wei, et al., A facile transformation of alkynes into
a-amino ketones by an N-bromosuccinimide-mediated