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Scheme 2 Reaction of electron-withdrawing alkyne with NBP–DBU
combination.
Scheme 5 Mechanistic proposal.
N-haloimides as both halogen and nitrogen sources, via the
DBU dual activation strategy. This aminohalogenation process
provided a new idea for the regio- and stereoselective synthesis
of cis-halogenated enamines. The mechanism for the formation
of alkynyl halides, subsequent nucleophilic addition and final
protonation was proposed. Starting from electron-poor internal
alkynes, enamines may be efficiently achieved. The reaction
features mild conditions, a relatively broad substrate scope,
readily available reagents, high efficiency and atom-economy.
Further work on the exploration of the DBU–N-haloimide system
in organic synthesis is ongoing.
Scheme 3 Reactions of arylacetylenes with N-haloimides.
To explore the scope of the halogen and nitrogen components,
the reactions of alkynes with other N-haloimides were conducted
(Scheme 3). In addition to NBP, N-bromogenic reagents including
NBS, 1,3-dibromo-5,5-dimethylhydantoin and N-bromosaccharin
were suitable for the reaction, and various imido-moieties were
successfully incorporated, affording products 4–6 in 61–73% yields.
When NCP was used, chloroenamine 7 was achieved in 45% yield.11
Halogenated enamine products 2–7 can be utilized as useful
synthetic building blocks for further transformation.12
Financial support from the National Natural Science Foundation
of China (Nos. 21172034 and 21372039) is gratefully acknowledged.
Notes and references
To elucidate the reaction mechanism, several control experi-
ments were performed (Scheme 4). In the absence of DBU, the
reaction did not take place at all, indicating that DBU plays a
vital role in the reaction (eqn (1)). In the reactions of selected
alkynes 1 with NBP and DBU performed at room temperature,
alkynyl bromides 8a–c were successfully isolated in good to
excellent yields (eqn (2)).13 The alkynyl bromides may further
react with phthalimide in the presence of DBU at 80 1C, giving
bromoenamines exclusively (eqn (3)). On the basis of all the
results described above, a possible mechanism for the halo-
enamidation of alkynes is proposed in Scheme 5. The process
involves the initial formation of alkynyl halides, subsequent
nucleophilic addition,14–16 and final protonation.17
1 (a) U. Wille, O. Kru¨ger, A. Kirsch and U. Lu¨ning, Eur. J. Org. Chem.,
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2 For transition metal catalyzed intramolecular alkyne aminohalogena-
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13, 4220; (b) T. Xu and G. Liu, Org. Lett., 2012, 14, 5416; (c) C. Jonasson,
A. Horvath and J.-E. Backvall, J. Am. Chem. Soc., 2000, 122, 9600.
3 (a) A. Wohl, Ber., 1919, 52, 51; (b) K. Ziegler, A. Spath, E. Schf,
W. Schumann and E. Winkelmann, Ann., 1942, 551, 80; (c) C. Djerassi,
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In conclusion, a simple, novel and efficient one-pot amino-
halogenation of terminal alkynes has been developed by using
4 Selected references: (a) M. Sasaki and A. K. Yudin, J. Am. Chem. Soc.,
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Y. Hui, J. Jiang, W. Wang, W. Chen, L. Lin and X. Feng, Angew. Chem.,
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85, 3129; (c) G. A. Russell and K. M. Desmond, J. Am. Chem. Soc.,
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6 (a) A. Alix, C. Lalli, P. Retailleau and G. Masson, J. Am. Chem. Soc., 2012,
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7 With NBS–DBU combination: (a) Y. Wei, S. Lin and F. Liang, Org. Lett.,
2012, 14, 4202; (b) Y. Wei, S. Lin, F. Liang and J. Zhang, Org. Lett., 2013,
15, 852; (c) Y. Wei, F. Liang and X. Zhang, Org. Lett., 2013, 15, 5186. With
NBS–carboxylic acid combination: (d) Y. Wei, S. Lin, J. Zhang, Z. Niu,
Scheme 4 Control experiments.
2362 | Chem. Commun., 2014, 50, 2360--2363
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