Progress of Difluoromethyl Heteroaryl Sulfones as Difluoroalkylation Reagents

doi:10.6023/cjoc201903063

Abstract

Due to the uniqueness of fluorine atom and C—F bond, difluoromethylene has special properties. As a bioisostere of an oxygen or a carbonyl group, it plays an important role in medicines, pesticides and materials. Difluoromethyl heteroaryl sulfones, represented by 2-PySO₂CF₂H (Hu reagent), have been developed recently as difluoromethylation reagents, and widely recognized by synthetic chemists for their ease of preparation, good functional group tolerance and universal applicability to a wide range of carbonyl compounds. Through different types of reactions such as nucleophilic substitution, nucleophilic addition, Julia-Kocienski olefination reaction, and radical-mediated difunctionalization, they introduced difluoromethyl, difluoromethylene, gem-difluoroalkene and other fluorine-containing groups into aldehydes, ketones, and heterocyclic compounds. For the first time, the synthesis of fluorine-containing organic compounds involved in various difluoromethyl heteroaryl sulfones in the past decade is reviewed from the perspective of reaction types and their application studies.

Key words: difluoromethyl heteroaryl sulfones, nucleophilic reaction, Julia-Kocienski olefination, radical-mediated difunctionalization

Cite this article

Tao Xuefen, Sheng Rong, Bao Kun, Wang Yuxin, Jin Yinxiu. Progress of Difluoromethyl Heteroaryl Sulfones as Difluoroalkylation Reagents[J]. Chinese Journal of Organic Chemistry, 2019, 39(10): 2726-2734.

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Fig. & Tab. 36

Figure 1. Biologically active molecules

Scheme 1. Julia-Kocienski olefination reaction

Scheme 2. gem-Difluoroolefination reaction with different sulfones

Figure 2. Difluoromethyl heteroaryl sulfones

Scheme 3. Proposed mechansism of olefination reaction

Scheme 4. Iododifluoromethlation of carbonyl compounds

Scheme 5. Bromodifluoromethylation of carbonyl compounds

Scheme 6. Proposed mechanism of halogen-difluoromethylation

Scheme 7. Julia-Kocienski reaction of isocyanates

Scheme 8. Proposed mechanism of Julia-Kocienski reaction of isocyanates

Scheme 9. Julia-Kocienski reaction of glycal

Scheme 10. Julia-Kocienski reaction of glycal

Scheme 11. One-pot Julia-Kocienski reaction of glycal

Scheme 12. Application of Julia-Kocienski reaction

Scheme 13. H+-mediated Julia-Kocienski reaction

Scheme 14. Julia-Kocienski reaction of diaryl ketones

Scheme 15. Julia-Kocienski reaction of aliphatic aldehydes

Scheme 16. Application of gem-difluoroalkene

Scheme 17. Application of difluoromethyl heteroaryl sulfone

Scheme 18. Nucleophilic addition to imines

Scheme 19. Reaction of various 2-pyridyl sulfones

Scheme 20. Iododifluoromethylation

Scheme 21. Application of iododifluoromethylation

Scheme 22. Nucleophilic fluoroalkylation

Scheme 23. Synthesis of difluorinated sulfonates

Scheme 24. Synthesis of di?uoroalkyl ketal sul?nate salt and its application

Scheme 25. Radical difluoromethylation

Scheme 26. Radical difluoromethylation

Scheme 27. Radical difluoromethylation

Scheme 28. Radical difluoromethylation

Scheme 29. Difluoromethyl radicalization

Scheme 30. Difluoromethyl radicalization

Scheme 31. Radical difunctionalization of alkenes

Scheme 32. Proposed mechanism of radical difunctionalization of alkenes

Scheme 33. Et3B/air initiated radical reaction

Scheme 34. ArSCF2 radical-triggered cyclization

References 47

[1]	Kanda, E . Bull. Chem. Soc. Jpn. 1937, 12, 469. doi: 10.1246/bcsj.12.469
[2]	Premchandran, R. H.; Ogletree, M. L.; Fried, J . J. Org. Chem. 1993, 58, 5724. doi: 10.1021/jo00073a035
[3]	Huchet, Q. A.; Kuhn, B.; Wagner, B.; Fischer, H.; Kansy, M.; Zimmerli, D.; Carreira, E. M.; Müller, K. J. Fluorine Chem. 2013, 152, 119. doi: 10.1016/j.jfluchem.2013.02.023
[4]	Liao, B.; Liao, Q. J. Prog. Pharm. Sci. 2012, 36, 138.(in Chinese).
	( 廖斌, 廖清江, 药学进展, 2012, 36, 138.)
[5]	Tan, C. B.; Shi, L. L.; Wang, S. W. Drugs Clin. 2013, 28, 415 (in Chinese).
	( 谭初兵, 时丽丽, 王士伟 , 现代药物与临床, 2013, 28, 415.)
[6]	Chen, L.; Zhao, T. X.; Zou, X. Chin. J. New Drug 2015, 24, 361(in Chinese).
	( 陈玲, 赵天笑, 邹栩 , 中国新药杂志, 2015, 24, 361.)
[7]	Zhang, J. Z. Shanghai Med. Pharm. J. 2015, 36, 79(in Chinese).
	( 张建忠, 上海医药, 2015, 36, 79.)
[8]	Xiao, Y. L.; Zhang, B.; Feng, Z.; Zhang, X. G. Org. Lett. 2014, 16, 4822. doi: 10.1021/ol502121m
[9]	Zhang, X. X.; Cao, S. Tetrahedron Lett. 2017, 58, 375. doi: 10.1016/j.tetlet.2016.12.054
[10]	Ni, C. F.; Hu, M. Y.; Hu, J. B. Chem. Revv. 2015, 115, 765.
[11]	Zhou, Q. Q.; Zou, Y. Q.; Lu, L. Q.; Xiao, W. J. Angew. Chem., Int. Ed. 2019, 58, 1586. doi: 10.1002/anie.201803102
[12]	Grushin, V. V. A. Chem. Res. 2010, 43, 160. doi: 10.1021/ar9001763
[13]	Hine, J.; Porter, J. J. J. Am. Chem. Soc. 1960, 82, 6178. doi: 10.1021/ja01508a050
[14]	Zhao, Y. C.; Huang, W. Z.; Zhu, L. G.; Hu, J. B. Org. Lett. 2010, 12, 1444. doi: 10.1021/ol100090r
[15]	Zhao, Y. C.; Gao, B.; Hu, J. B. J. Am. Chem. Soc. 2012, 134, 5790. doi: 10.1021/ja301601b
[16]	Li, S.; Peng, P.; Wei, J.; Hu, Y. Z.; Hu, J. B.; Sheng, R . Adv. Synth. Catal. 2015, 357, 3429. doi: 10.1002/adsc.201500150
[17]	Habib, S.; Gueyrard, D . Eur. J. Org. Chem. 2015,871.
[18]	Liu, X.; Yin, Q.; Yin, J.; Chen, G. H.; Wang, X.; You, Q. D.; Chen, Y. L.; Xiong, B.; Shen, J. K . Eur. J. Org. Chem. 2014,6150.
[19]	Moschitto, M. J.; Silverman, R. B . Org. Lett. 2018, 20, 4589. doi: 10.1021/acs.orglett.8b01872
[20]	Wang, X. P.; Lin, J. H.; Xiao, J. C.; Zheng, X . Eur. J. Org. Chem. 2014, 928.
[21]	Gao, B.; Zhao, Y. C.; Hu, M. Y.; Ni, C. F.; Hu, J. B. Chem. Eur. J. 2014, 20, 1. doi: 10.1002/chem.201390210
[22]	McAlpine, I.; Tran-Dubé, M.; Wang, F.; Scales, S.; Matthews, J.; Collins, M. R.; Nair, S. K.; Nguyen, M.; Bian, J. W.; Alsina, L. M.; Sun, J.; Zhong, J. Y.; Warmus, J. S.; O’Neill, B. T. J. Org. Chem. 2015, 80, 7266. doi: 10.1021/acs.joc.5b00853
[23]	Zhao, Y. C.; Zhang, L. J.; Xu, G. F.; Zheng, J.; Hu, J. B. Sci. China Chem. 2011, 41, 1833 (in Chinese).
	( 赵延川, 张丽君, 许国峰, 郑吉, 胡金波 , 中国科学•化学, 2011, 41, 1833.)
[24]	Prakash, G. K. S.; Ni, C. F.; Wang, F.; Zhang, Z.; Haiges, R Olah, G. A .; Angew. Chem., Int. Ed. 2013, 52, 10835. doi: 10.1002/anie.201304395
[25]	Miao, W. J.; Ni, C. F.; Zhao, Y. C.; Hu, J. B. Org. Lett. 2016, 18, 2766. doi: 10.1021/acs.orglett.6b01258
[26]	Prakash, G. K. S.; Ni, C. F.; Wang, F.; Hu, J. B.; George, A. O. Angew. Chem., Int. Ed. 2011, 50, 2559. doi: 10.1002/anie.201007594
[27]	Zhou, Q.; Gui, J.; Pan, C. M.; Albone, E.; Cheng, X.; Suh, E. M.; Grasso, L.; Ishihara, Y.; Baran, P. S . J. Am. Chem. Soc. 2013, 135, 12994. doi: 10.1021/ja407739y
[28]	Zhou, Q.; Ruffoni, A.; Gianatassio, R.; Fujiwara, Y.; Sella, E.; Shabat, D.; Baran, P. S. Angew. Chem. 2013, 125, 4041. doi: 10.1002/ange.v125.14
[29]	Gnaim, S.; Scomparin, A.; Li, X. L.; Baran, P. S.; Rader, C.; Ronit, S. F.; Shabat, D . Bioconjugate Chem. 2016, 27, 1965. doi: 10.1021/acs.bioconjchem.6b00382
[30]	Pintauer, T.; Matyjaszewski, K. Chem. Soc. Rev. 2008, 37, 1087. doi: 10.1039/b714578k
[31]	Eckenhoff, W. T.; Pintauer, T. Catal. Rev. 2010, 52, 1. doi: 10.1080/01614940903238759
[32]	Cao, M. Y.; Ren, X.; Lu, Z. Tetrahedron Lett. 2015, 56, 3732. doi: 10.1016/j.tetlet.2015.04.091
[33]	Chen, J. R.; Yu, X. Y.; Xiao, W. J. Synthesis 2015, 47, 604. doi: 10.1055/s-00000084
[34]	Yoon, T. P.; Ischay, M. A.; Du, J. Nat. Chem. 2010, 2, 527. doi: 10.1038/nchem.687
[35]	Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102. doi: 10.1039/B913880N
[36]	Xuan, J Xiao, W. J. .; Angew. Chem., Int. Ed. 2012, 51, 6828. doi: 10.1002/anie.201200223
[37]	Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322 doi: 10.1021/cr300503r
[38]	Koike, T.; Akita, M. Inorg. Chem. Front. 2014, 1, 561.
[39]	Rong, J.; Deng, L.; Tan, P.; Ni, C. F.; Gu, Y. C.; Hu, J. B. Angew. Chem., Int. Ed. 2016, 55, 2743. doi: 10.1002/anie.201510533
[40]	Zhu, M.; Fu, W. J.; Wang, Z. Q.; Xu, C.; Ji, B. M. Org. Biomol. Chem. 2017, 15, 9057. doi: 10.1039/C7OB02366A
[41]	Fu, W. J.; Han, X.; Zhu, M Xu, C.; Wang, Z. Q.; Ji, B. M.; Hao, X. Q.; Song, M .P. Chem. Commun. 2016, 52, 13413. doi: 10.1039/C6CC07771D
[42]	Zou, G. L.; Wang, X. L . Org. Biomol. Chem. 2017, 15, 8748. doi: 10.1039/C7OB02226C
[43]	He, Z. B.; Tan, P.; Ni, C. F.; Hu, J. B . Org. Lett. 2015, 17, 1838. doi: 10.1021/acs.orglett.5b00308
[44]	Miao, W. J.; Zhao, Y. C.; Ni, C. F.; Gao, B.; Zhang, W.; Hu, J. B. J. Am. Chem. Soc. 2018, 140, 880. doi: 10.1021/jacs.7b11976
[45]	Yu, J. J.; Wu, Z.; Zhu, C. Angew. Chem., Int. Ed. 2018, 57, 1.
[46]	Miao, W. J.; Ni, C. F.; Zhao, Y. C.; Hu, J. B. J. Fluorine Chem. 2014, 167, 231. doi: 10.1016/j.jfluchem.2014.05.012
[47]	Wei, J.; Gu, D. Y.; Wang, S. D.; Hu, J. B.; Dong, X. W.; Sheng, R. Org. Chem. Front. 2018, 5, 2568. doi: 10.1039/C8QO00644J

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