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Synthesis 2020; 52(02): 197-207
DOI: 10.1055/s-0039-1690714
short review
© Georg Thieme Verlag Stuttgart · New York

Recent Advances in Difluoromethylthiolation

Xuan Xiao §
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: [email protected]   Email: [email protected]
,
Zi-Tong Zheng §
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
,
Ting Li
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
,
Jing-Lin Zheng
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
,
Ting Tao
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
,
Li-Mei Chen
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
,
Jin-Ying Gu
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
,
Xu Yao∗
a  Group of Lead Compound, Institute of Pharmacy & Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, P. R. of China   Email: [email protected]
,
Jin-Hong Lin∗
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: [email protected]   Email: [email protected]
,
Ji-Chang Xiao∗
b  Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, P. R. of China   Email: [email protected]   Email: [email protected]
› Author AffiliationsWe thank the National Natural Science Foundation (21421002, 21672242), Key Research Program of Frontier Sciences, Chinese Academy of Sciences (QYZDJSSW-SLH049), and National Basic Research Program of China (2015CB931903), Hunan Graduate Science and Technology Innovation Projects (CX2018B585), the Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study (0223-0007-000004), the Undergraduate Research Learning and Innovative Experiment Project, University of South China (2019-100, 2018XJXZ188, 2018XJXZ350, 2018XJXZ194, 2018XJXZ351), the Guiding Project Of Hengyang Science and Technology Department (S2018F9031015299), Program for Innovative Talent Team of Hengyang (2017-1), the Key Project of Hengyang Science and Technology Department (2017KJ166) for financial support.
Further Information

Publication History

Received: 10 July 2019

Accepted after revision: 26 September 2019

Publication Date:
21 October 2019 (online)

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§ These authors contributed equally to this work.

Abstract

The difluoromethylthio group (HCF2S), which has been identified as a valuable functionality in drug and agrochemical discovery, has received increased attention recently. Two strategies, difluoromethylation and direct difluoromethylthiolation, have been well established for HCF2S incorporation. The former strategy suffers from the need to prepare sulfur-containing substrates. In contrast, direct difluoromethylthiolation is straightforward and step-economic. This short review covers the recent advances in direct difluoromethylthiolation, including electrophilic, radical, and transition-metal-catalyzed or -promoted reactions­.

1 Introduction

2 Electrophilic Difluoromethylthiolation

3 Radical Difluoromethylthiolation

4 Transition-Metal-Catalyzed or -Promoted Difluoromethylthiolation

5 Conclusions and Perspectives

Key words

difluoromethylthio group - difluoromethylthiolation - electrophilic - radical - fluorine
 

  • References

  • 1 Cahard D, Bizet V. Chem. Soc. Rev. 2014; 43: 135
  • 2 Thayer AM. Chem. Eng. News 2006; 84 (23): 15
  • 3 Organofluorine Chemistry . Uneyama K. Blackwell; Oxford: 2006
  • 4 Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications, 2nd ed. Wiley-VCH; Weinheim: 2013
    • 5a Fluorine in Medicinal Chemistry and Chemical Biology. Ojima I. Blackwell; Chichester: 2009
    • 5b Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432
    • 5c Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
  • 6 Xiong H.-Y, Pannecoucke X, Besset T. Chem. Eur. J. 2016; 22: 16734
  • 7 Rico I, Wakselhan C. Tetrahedron Lett. 1981; 22: 323
  • 8 Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165
  • 9 Zafrani Y, Yeffet D, Sod-Moriah G, Berliner A, Amir D, Marciano D, Gershonov E, Saphier S. J. Med. Chem. 2017; 60: 797
  • 10 Ito M, Ishigami T. Infection 1991; 19: S253
  • 11 Fourie JJ, Horak IG, de la Puente Redondo V. Vet. Rec. 2010; 167: 442
  • 12 Jeanmart S, Edmunds AJ. F, Lamberth C, Pouliot M. Bioorg. Med. Chem. 2016; 24: 317
  • 13 Yoshimura T, Ikeuchi T, Ohno S, Asakura S, Hamada Y. J. Pestic. Sci. 2013; 38: 171
  • 14 Morita K, Ide K, Hayase Y, Takahashi T, Hayashi Y. Agric. Biol. Chem. 1987; 51: 1339
  • 15 Wu J, Gu Y, Leng X, Shen Q. Angew. Chem. Int. Ed. 2015; 54: 7648
    • 16a Bootwicha T, Liu X, Pluta R, Atodiresei I, Rueping M. Angew. Chem. Int. Ed. 2013; 52: 12856
    • 16b Shao X, Xu C, Lu L, Shen Q. Acc. Chem. Res. 2015; 48: 1227
  • 17 Zhu D, Gu Y, Lu L, Shen Q. J. Am. Chem. Soc. 2015; 137: 10547
  • 18 Shen F, Zhang P, Lu L, Shen Q. Org. Lett. 2017; 19: 1032
  • 19 Xu W, Ma J, Yuan X.-A, Dai J, Xie J, Zhu C. Angew. Chem. Int. Ed. 2018; 57: 10357
    • 20a Roberts BP. Chem. Soc. Rev. 1999; 28: 25
    • 20b Le C, Liang Y, Evans RW, Li X, MacMillan DW. C. Nature 2017; 547: 79
    • 21a Ferry A, Billard T, Langlois BR, Bacqué E. J. Org. Chem. 2008; 73: 9362
    • 21b Ferry A, Billard T, Langlois BR, Bacque E. Angew. Chem. Int. Ed. 2009; 48: 8551
    • 21c Alazet S, Zimmer L, Billard T. Chem. Eur. J. 2014; 20: 8589
  • 22 Ismalaj E, Le Bars D, Billard T. Angew. Chem. Int. Ed. 2016; 55: 4790
  • 23 Xiong H.-Y, Bayle A, Pannecoucke X, Besset T. Angew. Chem. Int. Ed. 2016; 55: 13490
  • 24 Huang Z, Matsubara O, Jia S, Tokunaga E, Shibata N. Org. Lett. 2017; 19: 934
  • 25 Yan Q, Jiang L, Yi W, Liu Q, Zhang W. Adv. Synth. Catal. 2017; 359: 2471
  • 26 Jiang L, Yi W, Liu Q. Adv. Synth. Catal. 2016; 358: 3700
    • 27a Moore GG. I. J. Org. Chem. 1979; 44: 1708
    • 27b Tang X.-J, Thomoson CS, Dolbier WR. Jr. Org. Lett. 2014; 16: 4594
  • 28 Zhao X, Li T, Yang B, Qiu D, Lu K. Tetrahedron 2017; 73: 3112
  • 29 Zhao X, Wei A, Li T, Su Z, Chen J, Lu K. Org. Chem. Front. 2017; 4: 232
  • 30 Jiang L, Ding T, Yi W.-B, Zeng X, Zhang W. Org. Lett. 2018; 20: 2236
  • 31 Jiang L, Yan Q, Wang R, Ding T, Yi W, Zhang W. Chem. Eur. J. 2018; 24: 18749
    • 32a Zheng J, Wang L, Lin J.-H, Xiao J.-C, Liang SH. Angew. Chem. Int. Ed. 2015; 54: 13236
    • 32b Zheng J, Cheng R, Lin J.-H, Yu DH, Ma L, Jia L, Zhang L, Wang L, Xiao J.-C, Liang SH. Angew. Chem. Int. Ed. 2017; 56: 3196
    • 32c Luo J.-J, Zhang M, Lin J.-H, Xiao J.-C. J. Org. Chem. 2017; 82: 11206
  • 33 Yu J, Lin J.-H, Xiao J.-C. Angew. Chem. Int. Ed. 2017; 56: 16669
    • 34a Zheng J, Cai J, Lin J.-H, Guo Y, Xiao J.-C. Chem. Commun. 2013; 49: 7513
    • 34b Zheng J, Lin J.-H, Cai J, Xiao J.-C. Chem. Eur. J. 2013; 19: 15261
    • 34c Deng X.-Y, Lin J.-H, Zheng J, Xiao J.-C. Chem. Commun. 2015; 51: 8805
  • 35 Zhu D, Shao X, Hong X, Lu L, Shen Q. Angew. Chem. Int. Ed. 2016; 55: 15807
  • 36 Xu B, Wang D, Hu Y, Shen Q. Org. Chem. Front. 2018; 5: 1462
  • 37 Larsson K, Rosenhall L. Clin. Exp. Allergy 1996; 26: 18
  • 38 Xu B, Li D, Lu L, Wang D, Hu Y, Shen Q. Org. Chem. Front. 2018; 5: 2163
  • 39 Guo S.-H, Zhang X.-L, Pan G.-F, Zhu X.-Q, Gao Y.-R, Wang Y.-Q. Angew. Chem. Int. Ed. 2018; 57: 1663
    • 40a Wu X, Chu L, Qing FL. Angew. Chem. Int. Ed. 2013; 52: 2198
    • 40b Mizuta S, Verhoog S, Engle KM, Khotavivattana T, O’Duill M, Wheelhouse K, Rassias G, Medebielle M, Gouverneur V. J. Am. Chem. Soc. 2013; 135: 2505
    • 40c Lin Q.-Y, Xu X.-H, Zhang K, Qing F.-L. Angew. Chem. Int. Ed. 2016; 55: 1479
    • 40d Meyer CF, Hell SM, Misale A, Trabanco AA, Gouverneur V. Angew. Chem. Int. Ed. 2019; 58: 8829
    • 40e Wu W, Dai W, Ji X, Cao S. Org. Lett. 2016; 18: 2918
  • 41 Shao X, Hong X, Lu L, Shen Q. Tetrahedron 2019; 75: 4156
    • 42a Prier CK, Rankic DA, MacMillan DW. C. Chem. Rev. 2013; 113: 5322
    • 42b Ravelli D, Protti S, Fagnoni M. Chem. Rev. 2016; 116: 9850
  • 43 Li J, Zhu D, Lv L, Li C.-J. Chem. Sci. 2018; 9: 5781
  • 44 Wang W, Zhang S, Zhao H, Wang S. Org. Biomol. Chem. 2018; 16: 8565
  • 45 Li H, Cheng Z, Tung C.-H, Xu Z. ACS Catal. 2018; 8: 8237
    • 46a Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457
    • 46b Hayashi T, Yamasaki K. Chem. Rev. 2003; 103: 2829
    • 46c Candeias NR, Montalbano F, Cal PM. S. D, Gois PM. P. Chem. Rev. 2010; 110: 6169
    • 47a Seiple IB, Su S, Rodriguez RA, Gianatassio R, Fujiwara Y, Sobel AL, Baran PS. J. Am. Chem. Soc. 2010; 132: 13194
    • 47b Dickschat A, Studer A. Org. Lett. 2010; 12: 3972
    • 47c Sorin G, Martinez Mallorquin R, Contie Y, Baralle A, Malacria M, Goddard J.-P, Fensterbank L. Angew. Chem. Int. Ed. 2010; 49: 8721
    • 47d Huang H, Zhang G, Gong L, Zhang S, Chen Y. J. Am. Chem. Soc. 2014; 136: 2280
  • 48 Liu W, Liu P, Lv L, Li C.-J. Angew. Chem. Int. Ed. 2018; 57: 13499
  • 49 Candish L, Pitzer L, Gómez-Suárez A, Glorius F. Chem. Eur. J. 2016; 22: 4753
  • 50 Gu Y, Leng X, Shen Q. Nat. Commun. 2014; 5: 5405
  • 51 Wu J, Liu Y, Lu C, Shen Q. Chem. Sci. 2016; 7: 3757
  • 52 Wu J, Lu C, Lu L, Shen Q. Chin. J. Chem. 2018; 36: 1031
  • 53 Yang Y.-D, Azuma A, Tokunaga E, Yamasaki M, Shiro M, Shibata N. J. Am. Chem. Soc. 2013; 135: 8782
  • 54 Arimori S, Matsubara O, Takada M, Shiro M, Shibata N. R. Soc. Open Sci. 2016; 3: 160102
  • 55 Kondo H, Maeno M, Sasaki K, Guo M, Hashimoto M, Shiro M, Shibata N. Org. Lett. 2018; 20: 7044
  • 56 Gondo S, Matsubara O, Chachignon H, Sumii Y, Cahard D, Shibata N. Molecules 2019; 24: 221