A Convenient Strategy for Remote C–H Bond Halogenation of 8-Aminoquinolines in the C5 Position

^◊ These two authors contributed equally to this work.

Abstract

A highly efficient and convenient strategy has been developed for remote C–H bond halogenation of 8-aminoquinolines in good to excellent yields under transition-metal-free conditions. The reaction tolerates a variety of functional groups and can potentially be scaled up.

Key words

transition-metal-free - halogenation - C–H bond functionalization - aminoquinolines - regioselectivity - potassium persulfate

• References

• 1a Hughes CC. MacMillan JB. Gaudêncio SP. Jensen PR. Fenical W. Angew. Chem. Int. Ed. 2009; 48: 725
• 1b Pan E. Oswald NW. Legako AG. Life JM. Posner BA. MacMillan JB. Chem. Sci. 2013; 4: 482
• 1c Pandey RR. Srivastava A. Malasoni R. Naqvi A. Jain A. Maikhuri JP. Paliwal S. Gupta G. Dwivedi AK. Bioorg. Med. Chem. Lett. 2012; 22: 5735
• 1d Vandekerckhove S. Müller C. Vogt D. Lategan C. Smith PJ. Chibale K. De Kimpe N. D’hooghe M. Bioorg. Med. Chem. Lett. 2013; 23: 318
• 1e Vandekerckhove S. Tran HG. Desmet T. D’hooghe M. Bioorg. Med. Chem. Lett. 2013; 23: 4641
• 2a He J. Takise R. Fu H. Yu J.-Q. J. Am. Chem. Soc. 2015; 137: 4618
• 2b Miyaji R. Asano K. Matsubara S. Org. Biomol. Chem. 2014; 12: 119
• 2c Deng Y. Gong W. He J. Yu J.-Q. Angew. Chem. Int. Ed. 2014; 53: 6692
• 2d Miyaji R. Asano K. Matsubara S. J. Am. Chem. Soc. 2015; 137: 6766
• 3a Eicher T. Hauptmann S. The Chemistry of Heterocycles: Structure, Reactions, Syntheses, and Applications. Wiley-VCH; Weinheim: 2003. 2nd ed.
• 3b Michael JP. Nat. Prod. Rep. 2008; 25: 166
• 3c Solomon VR. Lee H. Curr. Med. Chem. 2011; 18: 1488
• 4a Chen Y.-L. Huang C.-J. Huang Z.-Y. Tseng C.-H. Chang F.-S. Yang S.-H. Lin S.-R. Tzeng C.-C. Bioorg. Med. Chem. 2006; 14: 3098
• 4b Ghorab MM. Ragab FA. Hamed MM. Eur. J. Med. Chem. 2009; 44: 4211
• 4c Kaur K. Jain M. Reddy RP. Jain R. Eur. J. Med. Chem. 2010; 45: 3245
• 4d Colomb J. Becker G. Fieux S. Zimmer L. Billard T. J. Med. Chem. 2014; 57: 3884
• 5 For a review on the site selective C–H functionalization of quinolines, see: Iwai T. Sawamura M. ACS Catal. 2015; 5: 5031

For selected examples of C–H functionalizations at the C2-position of quinolines, see:
• 6a Berman AM. Lewis JC. Bergman RG. Ellman JA. J. Am. Chem. Soc. 2008; 130: 14926
• 6b Tobisu M. Hyodo I. Chatani N. J. Am. Chem. Soc. 2009; 131: 12070
• 6c Seiple IB. Su S. Rodriguez RA. Gianatassio R. Fujiwara Y. Sobel AL. Baran PS. J. Am. Chem. Soc. 2010; 132: 13194
• 6d Ren X. Wen P. Shi X. Wang Y. Li J. Yang S. Yan H. Huang G. Org. Lett. 2013; 15: 5194
• 6e Zhu C. Yi M. Wei D. Chen X. Wu Y. Cui X. Org. Lett. 2014; 16: 1840
• 6f Xia X.-F. Zhu S.-L. Gu Z. Wang H. RSC Adv. 2015; 5: 28892

For selected examples of C–H functionalizations at the C4-position of quinolines, see:
• 7a Deng G. Li C.-J. Org. Lett. 2009; 11: 1171
• 7b Tsai C.-C. Shih W.-C. Fang C.-H. Li C.-Y. Ong T.-G. Yap GP. A. J. Am. Chem. Soc. 2010; 132: 11887
• 7c Wasa M. Worrell BT. Yu J.-Q. Angew. Chem. Int. Ed. 2010; 49: 1275
• 7d Chen Q. du Jourdin XM. Knochel P. J. Am. Chem. Soc. 2013; 135: 4958
• 7e Yamamoto S. Saga Y. Andou T. Matsunaga S. Kanai M. Adv. Synth. Catal. 2014; 356: 401

For selected examples of C–H functionalizations at the C8-position of quinolines, see:
• 8a Kwak J. Kim M. Chang S. J. Am. Chem. Soc. 2011; 133: 3780
• 8b Sharma U. Park Y. Chang S. J. Org. Chem. 2014; 79: 9899
• 8c Hwang H. Kim J. Jeong J. Chang S. J. Am. Chem. Soc. 2014; 136: 10770
• 8d Stephens DE. Lakey-Beitia J. Atesin AC. Ateşin TA. Chavez G. Arman HD. Larionov OV. ACS Catal. 2015; 5: 167
• 9a Suess AM. Ertem MZ. Cramer CJ. Stahl SS. J. Am. Chem. Soc. 2013; 135: 9797
• 9b Cong X. Zeng X. Org. Lett. 2014; 16: 3716
• 9c Qiao H. Sun S. Yang F. Zhu Y. Zhu W. Dong Y. Wu Y. Kong X. Jiang L. Wu Y. Org. Lett. 2015; 17: 6086
• 9d Liang H.-W. Jiang K. Ding W. Yuan Y. Shuai L. Chen Y.-C. Wei Y. Chem. Commun. 2015; 51: 16928
• 9e Sahoo H. Reddy MK. Baidya I. Ramakrishna M. Chem. Eur. J. 2016; 22: 1592
• 9f Xu J. Shen C. Zhu X. Zhang P. Ajitha MJ. Huang K.-W. An Z. Liu X. Chem. Asian. J. 2016; 11: 882
• 9g Xu J. Zhu X. Zhou G. Ying B. Ye P. Su L. Shen C. Zhang P. Org. Biomol. Chem. 2016; 14: 3016
• 9h Wu C. Zhou H. Wu Q. He M. Li P. Su Q. Mu Y. Synlett 2016; 27: 868
• 9i Zhu L. Qiu R. Cao X. Xiao S. Xu X. Au C.-T. Yin S.-F. Org. Lett. 2015; 17: 5528
• 9j Chen H. Li P. Wang M. Wang L. Org. Lett. 2016; 18: 4794
• 9k Whiteoak CJ. Planas O. Company A. Ribas X. Adv. Synth. Catal. 2016; 358: 1679
• 9l He Y. Zhao N. Qiu L. Zhang X. Fan X. Org. Lett. 2016; 18: 6054
• 10a Tanabe K. Chen HE. Verma BL. Saggiomo AJ. Nodiff EA. J. Med. Chem. 1978; 21: 133
• 10b Dua VK. Sinha SN. Biswas S. Valecha N. Puri SK. Sharma VP. Bioorg. Med. Chem. Lett. 2002; 12: 3587
• 10c Wienser J. Ortmann R. Jomaa H. Schlitzer M. Angew. Chem. Int. Ed. 2003; 42: 5274
• 10d Tekwani BL. Walker LA. Curr. Opin. Infect. Dis. 2006; 19: 623
• 10e Hughes CC. Fenical WJ. J. Am. Chem. Soc. 2010; 132: 2528
• 10f Koh EJ. El-Gamal MI. Oh C.-H. Lee SH. Sim T. Kim G. Choi HS. Hong JH. Lee S.-g. Yoo KH. Eur. J. Med. Chem. 2013; 70: 10
• 10g Takayama Y. Yamada T. Tatekabe S. Nagasawa K. Chem. Commun. 2013; 49: 6519
• 10h Frisch KC. Bogert MT. J. Org. Chem. 1944; 9: 338
• 11a Ji D. He X. Xu Y. Xu Z. Bian Y. Liu W. Zhu Q. Xu Y. Org. Lett. 2016; 18: 4478
• 11b Wu Z. He Y. Ma C. Zhou X. Liu X. Li Y. Hu T. Wen P. Huang G. Asian J. Org. Chem. 2016; 5: 724
• 11c During the preparation of this manuscript, a similar transition-metal-free oxidative C5 C–H halogenation of 8-aminoquinoline amides has been reported, see: Wang Y. Wang Y. Jiang K. Zhang Q. Li D. Org. Biomol. Chem. 2016; 14: 10180
• 12 N-(5-Chloroquinolin-8-yl)benzamide (2aa); Typical Procedure A mixture of N-(quinolin-8-yl)benzamide (0.2 mmol, 49.6 mg, 1.0 equiv), LiCl (0.3 mmol, 12.7 mg, 1.5 equiv), and K₂S₂O₈ (108 mg, 0.4 mmol, 2 equiv) in MeCN was stirred under argon at 80 °C for 8 h, then cooled to r.t. The solvent was removed under reduced pressure, and the residue was purified by flash chromatography (silica gel, PE–EA = 20:1) to give a white solid that was dried under an oil-pump vacuum; yield: 43.4 mg (82%); mp 133–134 °C. ¹H NMR (400 MHz, CDCl₃): δ = 10.68 (s, 1 H), 8.89–8.87 (m, 2 H), 8.57 (d, J = 8.0 Hz, 1 H), 8.07 (d, J = 8.0 Hz, 2 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.60–7.53 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 165.36, 148.72, 139.22, 134.79, 133.79, 133.42, 131.98, 128.81, 127.24, 125.94, 124.44, 122.38, 116.39. HRMS (ESI): m/z [M + Na]⁺ Calcd for C₁₆H₁₁ClN₂NaO⁺: 305.0458; found: 305.0427.
• 13 Li J.-M. Weng J. Lu G. Chan AS. C. Tetrahedron Lett. 2016; 57: 2121
• 14 Son J.-H. Pudenz MA. Hoefelmeyer JD. Dalton Trans. 2010; 39: 11081
• 15 Tran C. Gallavardin T. Petit M. Slimi R. Dhimane H. Blanchard-Desce M. Acher FC. Ogden D. Dalko PI. Org. Lett. 2015; 17: 402
• 16 Lee IY. C. Jung MH. Lim H.-J. Lee HW. Heterocycles 2005; 65: 2505