Citation: WANG Zhen, LI En, HE Zhiqi, CHEN Jiean, HUANG Yong. Dehydrogenative Annulation of γ, δ-Unsaturated Amides and Alkynes via Double C―H Activation[J]. Acta Physico-Chimica Sinica, ;2019, 35(9): 906-912. doi: 10.3866/PKU.WHXB201811038 shu

Dehydrogenative Annulation of γ, δ-Unsaturated Amides and Alkynes via Double C―H Activation

WANG Zhen ^§ ,
LI En ^§ ,
HE Zhiqi ,
CHEN Jiean ^, ,
HUANG Yong ^,

State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Shenzhen Graduate School, Peking University, Shenzhen 518055, Guangdong Province, P. R. China

Corresponding author: CHEN Jiean, chenja@pkusz.edu.cn HUANG Yong, huangyong@pkusz.edu.cn
Received Date: 27 November 2018
Revised Date: 12 December 2018
Accepted Date: 21 December 2018
Available Online: 21 September 2018
Fund Project: The project was supported by the National Natural Science Foundation of China 21825101Shenzhen Basic Research Program, China JCYJ20170818085438996The project was supported by the National Natural Science Foundation of China 21572004The project was supported by the National Natural Science Foundation of China 21602007Shenzhen Basic Research Program, China JCYJ20170818085510474The project was supported by the National Natural Science Foundation of China (21825101, 21572004, 21602007), Shenzhen Basic Research Program, China (JCYJ20170818085510474, JCYJ20170818085438996)

Pyridones represent an important family of heterocycles that exhibit a wide range of biological activities. They are often found in pharmaceutical agents and biomolecules. Several transition-metal-catalyzed transformations have been developed to access this family of heterocycles. Among them, C―H bond activation has recently emerged as a general strategy for the construction of substituted pyridones. In most cases, the core nitrogen-containing heterocycle is assembled via the dehydrogenative annulation of α, β-unsaturated amides and alkynes. Such processes involve a cascade sequence of N―H cleavage, sp² C―H activation, and annulation. Despite this progress, the more readily available α, β-saturated amides are rarely used. Ideally, tethering the direct dehydrogenation of an amide with the above-mentioned C―H annulation cascade would give a more practical synthesis of pyridones. Nevertheless, the dehydrogenation of amides under mild conditions is a synthetic challenge due to their intrinsic weak α-acidity. Recently, we have reported a general protocol for the aerobic dehydrogenation of γ, δ-unsaturated amides, acids, and ketones. A key Ir―allyl intermediate was believed responsible for enhancing the α-acidity of the amides studied, which enables the dehydrogenation step to occur under mild reaction conditions. Herein, we describe a new method for the synthesis of polysubstituted pyridones using γ, δ-unsaturated amides and alkynes. In the presence of [RhCp*Cl₂]₂, the dehydrogenation step occurs via β-C―H bond activation. The resulting π-allyl―Rh intermediate undergoes an accelerated dehydrogenation reaction to afford the doubly unsaturated amide. This in-situ generated dienamide undergoes sp² C―H activation at the β-position and a subsequent alkyne insertion/cyclization reaction to yield the target heterocycle. Regeneration of the Rh catalyst is accomplished using an external oxidant and completes the streamlined double C―H activation and double dehydrogenation catalytic cycle. Various functional groups are well tolerated. The γ-alkenyl moiety not only facilitates the direct dehydrogenation of amides, but also serves as a handle for further derivatization of the as-obtained products. To gain a mechanistic insight into the reaction cascade, a set of control experiments were carried out. The results demonstrate that the dienamide is one of the key reaction intermediates. NMR experiments confirmed that the fast dehydrogenation process occurs during the early stage of the reaction. The alkyne insertion is believed to be the rate-determining step in the reaction cascade, as suggested by competition experiments.
- Rh(III) catalysis,
- C―H activation,
- Dehydrogenation,
- Annulation,
1. [1]
  Kozikowski, A. P.; Tückmantel, W. Acc. Chem. Res. 1999, 32, 641. doi: 10.1021/ar9800892 doi: 10.1021/ar9800892
2. [2]
  Wall, M. E.; Wani, M. C.; Cook, C. E.; Palmer, K. H.; McPhail, A. T.; Sim, G. A. J. Am. Chem. Soc. 1966, 88, 3888. doi: 10.1021/ja00968a057 doi: 10.1021/ja00968a057
3. [3]
  Mitscher, L. A. Chem. Rev. 2005, 105, 559. doi: 10.1021/cr030101q doi: 10.1021/cr030101q
4. [4]
  Jessen, H. J.; Gademann, K. Nat. Prod. Rep. 2010, 27, 1168. doi: 10.1039/B911516C doi: 10.1039/B911516C
5. [5]
  Bergman, R. G. Nature 2007, 446, 391. doi: 10.1038/446391a doi: 10.1038/446391a
6. [6]
  Ackermann, L. Chem. Rev. 2011, 111, 1315. doi: 10.1021/cr100412j doi: 10.1021/cr100412j
7. [7]
  Corey, J. Y. Chem. Rev. 2011, 42, 863. doi: 10.1021/cr900359c doi: 10.1021/cr900359c
8. [8]
  Varela, J. A.; Saá, C. Chem. Rev. 2003, 103, 3787. doi: 10.1021/cr030677f doi: 10.1021/cr030677f
9. [9]
  Li, B.; Dixneuf, P. H. Chem. Soc. Rev. 2013, 42, 5744. doi: 10.1039/C3CS60020C doi: 10.1039/C3CS60020C
10. [10]
  Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. doi: 10.1021/cr900184e doi: 10.1021/cr900184e
11. [11]
  Guo, X. -X.; Gu, D. -W.; Wu, Z.; Zhang, W. Chem. Rev. 2015, 115, 1622. doi: 10.1021/cr500410y doi: 10.1021/cr500410y
12. [12]
  Su, Y.; Zhao, M.; Han, K.; Song, G.; Li, X. Org. Lett. 2010, 12, 5462. doi: 10.1021/ol102306c doi: 10.1021/ol102306c
13. [13]
  Hyster, T. K.; Rovis, T. J. Am. Chem. Soc. 2010, 132, 10565. doi: 10.1021/ja103776u doi: 10.1021/ja103776u
14. [14]
  Ackermann, L.; Lygin, A. V.; Hofmann, N. Org. Lett. 2011, 13, 3278. doi: 10.1021/ol201244s doi: 10.1021/ol201244s
15. [15]
  Shankar, M.; Guntreddi, T.; Ramesh, E.; Sahoo, A. K. Org. Lett. 2017, 19, 5665. doi: 10.1021/acs.orglett.7b02824 doi: 10.1021/acs.orglett.7b02824
16. [16]
  Tulichala, R. N. P.; Shankar, M.; Swamy, K. C. K. J. Org. Chem. 2017, 82, 5068. doi: 10.1021/acs.joc.7b00008 doi: 10.1021/acs.joc.7b00008
17. [17]
  Yu, Y.; Huang, L.; Wu, W.; Jiang, H. Org. Lett. 2014, 16, 2146. doi: 10.1021/ol500611d doi: 10.1021/ol500611d
18. [18]
  Matsubara, T.; Ilies, L.; Nakamura, E. Chem. Asian J. 2015, 11, 380. doi: 10.1002/asia.201501095 doi: 10.1002/asia.201501095
19. [19]
  Chen, Y.; Turlik, A.; Newhouse, T. R. J. Am. Chem. Soc. 2016, 138, 1166. doi: 10.1021/jacs.5b12924 doi: 10.1021/jacs.5b12924
20. [20]
  Chen, M.; Dong, G. J. Am. Chem. Soc. 2017, 139, 7757. doi: 10.1021/jacs.7b04722 doi: 10.1021/jacs.7b04722
21. [21]
  Chen, M.; Alexander, J. R.; Dong, G. Angew. Chem. Int. Ed. 2018, 57, 16205. doi: 10.1002/anie.201811197 doi: 10.1002/anie.201811197
22. [22]
  Wang, Z.; He, Z.; Zhang, L.; Huang, Y. J. Am. Chem. Soc. 2018, 140, 735. doi: 10.1021/jacs.7b11351 doi: 10.1021/jacs.7b11351
23. [23]
  Hyster, T. K.; Rovis, T. Chem. Sci. 2011, 2, 1606. doi: 10.1039/clsc00235j doi: 10.1039/clsc00235j
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