Synthesis 2017; 49(13): 2865-2872
DOI: 10.1055/s-0036-1590503
feature
© Georg Thieme Verlag Stuttgart · New York

Copper-Mediated sp 2 C–H Chlorination with Trichloroacetamide Using a Removable Directing Group

Wan-Chen Cindy Lee
Department of Chemistry, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA   Email: jjli@usfca.edu
,
Arya Tehrani
Department of Chemistry, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA   Email: jjli@usfca.edu
,
Department of Chemistry, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117, USA   Email: jjli@usfca.edu
› Author Affiliations
Further Information

Publication History

Received: 05 May 2017

Accepted: 08 May 2017

Publication Date:
15 May 2017 (online)

Dedicated to Prof. David R. Williams at Indiana University

Abstract

2-Aminophenyl-1H-pyrazole was discovered as a removable, bidentate directing group for copper-mediated aerobic oxidative sp 2 C–H bond chlorination employing trichloroacetamide as a new chlorine source. When Cu(OAc)2 was employed as the copper source, 1,1,3,3-­tetramethylguanidine (TMG) as an organic base, the reaction, optimally carried out overnight in DMSO at 80 °C in open air, produced a variety of mono- and dichlorinated products in moderate to excellent yields. This directing group can be removed oxidatively with cerium ammonium nitrate (CAN).

Supporting Information

 
  • References

  • 1 Oshiro Y. Sato S. Kurahashi N. Tanaka T. Kikuchi T. Tottori K. Uwahodo Y. Nishi T. J. Med. Chem. 1998; 41: 658
  • 2 Carini DJ. Duncia JV. Aldrich PE. Chiu AT. Johnson AL. Pierce ME. Price 3rd WA. Santella JB. Wells GJ. Wexler RR. Wong PC. Yoo S.-E. Timmermans PB. J. Med. Chem. 1991; 34: 2525
  • 3 Lee W.-CC. Shen Y. Gutierrez DA. Li JJ. Org. Lett. 2016; 18: 2660

    • A combination of PPh3/CCl3CONH2 was employed to chlorinate alcohols by converting C–OH bonds to C–Cl bonds:
    • 4a Das B. Chowdhury N. Damodar K. Ravikanth B. Helv. Chim. Acta 2007; 90: 2037
    • 4b Bluempaunupat W. Chantarasriwong O. Taboonpong P. Jang DO. Chavasiru W. Tetrahedron Lett. 2007; 48: 223
    • 4c Bluempaunupat W. Chavasiru W. Tetrahedron Lett. 2006; 47: 6821

      Palladium-catalyzed C–H chlorination:
    • 5a Dick AR. Hull KL. Sanford MS. J. Am. Chem. Soc. 2004; 126: 2300
    • 5b Bedford RB. Haddow MF. Mitchell CJ. Webster RL. Angew. Chem. Int. Ed. 2011; 50: 5524
    • 5c Rit RK. Yadav R. Ghosh K. Shankar M. Sahoo AK. Org. Lett. 2014; 16: 5258
    • 5d Zhang G. Sun S. Yang F. Zhang Q. Kang J. Wu Y. Wu Y. Adv. Synth. Catal. 2015; 357: 450
    • 5e Guo H. Chen M. Jiang P. Chen J. Pan L. Wang M. Xie C. Zhang Y. Tetrahedron 2015; 71: 70
    • 5f Testa C. Gigot É. Genc S. Decréau R. Roger J. Hierso J.-C. Angew. Chem. Int. Ed. 2016; 55: 5555
    • 5g Moghaddam FM. Tavakoli G. Saeednia B. Langer P. Jafari B. J. Org. Chem. 2016; 81: 3868

      Copper-mediated nucleophilic C–H chlorination:
    • 7a Chen X. Hao X.-S. Goodhue CE. Yu JQ. J. Am. Chem. Soc. 2006; 128: 6790
    • 7b Menini L. da Cruz Santos JC. Gusevskayaa EV. Adv. Synth. Catal. 2008; 350: 2052
    • 7c Lu Y. Wang R. Qiao X. Shen Z. Synlett 2011; 1038
    • 7d Mo S. Zhu YM. Shen ZM. Org. Biomol. Chem. 2013; 11: 2756
    • 7e Suess AM. Ertem MZ. Cramer CJ. Stahl SS. J. Am. Chem. Soc. 2013; 135: 9797
    • 7f Zhao J. Cheng X. Le J. Yang W. Xue F. Zhang X. Jiang C. Org. Biomol. Chem. 2015; 13: 9000
    • 7g Guo H. Chen M. Jiang P. Chen J. Pan L. Wang M. Xie C. Zhang Y. Tetrahedron 2015; 71: 70

      Copper-mediated electrophilic C–H chlorination:
    • 8a Wang WH. Pan CD. Chen F. Cheng J. Chem. Commun. 2011; 47: 3978
    • 8b Urones B. Martínez ÁM. Rodríguez N. Carretero JC. Chem. Commun. 2013; 49: 11044
    • 8c Du Z.-J. Gao L.-X. Lin Y.-J. Han F.-S. ChemCatChem 2014; 6: 123
    • 8d Du Z.-J. Gao L.-X. Shi B.-F. Chem. Commun. 2015; 51: 5093
  • 9 Lapointe D. Fagnou K. Chem. Lett. 2010; 39: 1118
    • 10a Shang M. Sun S.-Z. Dai H.-X. Yu J.-Q. J. Am. Chem. Soc. 2014; 136: 3354
    • 10b Talbot EP. A. Fernandes T. deA. McKenna JM. Toste FD. J. Am. Chem. Soc. 2014; 136: 4101
    • 11a Truong T. Klimovica K. Daugulis O. J. Am. Chem. Soc. 2013; 135: 9342
    • 11b Shabashov D. Daugulis O. J. Am. Chem. Soc. 2010; 132: 3965
  • 12 Gui Q. Chen X. Hu L. Wang D. Liu J. Tan Z. Adv. Synth. Catal. 2016; 358: 509
  • 13 Shang M. Wang H.-L. Sun S.-Z. Dai H.-X. Yu J.-Q. J. Am. Chem. Soc. 2014; 136: 11590
  • 14 He G. Zhang S.-Y. Nack WA. Li Q. Chen G. Angew. Chem. Int. Ed. 2013; 52: 11330
  • 15 Shang M. Sun S.-Z. Dai H.-X. Yu J.-Q. Org. Lett. 2014; 16: 5666
  • 16 Berger M. Chauhan R. Rodrigues CA. B. Maulide M. Chem. Eur. J. 2016; 22: 16805
    • 17a Yang LJ. Lu Z. Stahl SS. Chem. Commun. 2009; 6460
    • 17b King AE. Huffman LM. Casitas A. Costas M. Ribas X. Stahl SS. J. Am. Chem. Soc. 2010; 132: 12068
  • 18 See reference 3 for cost calculation and comparison.