Copper-Catalyzed Direct C-5 Fluorination of 8-Aminoquinolines by Remote C–H Activation

Si-Si Luo; Lan-Jun Su; Yue Jiang; Xiao-Bao Li; Zheng-Hui Li; Huan Sun; Ji-Kai Liu

doi:10.1055/s-0037-1610130

Synlett, Table of Contents

Synlett 2018; 29(11): 1525-1529
DOI: 10.1055/s-0037-1610130

letter

Copper-Catalyzed Direct C-5 Fluorination of 8-Aminoquinolines by Remote C–H Activation

Authors

Si-Si Luo

^aSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, P. R. of China Email: sunh15@163.com Email: jkliu@mail.kib.ac.cn
Lan-Jun Su

^aSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, P. R. of China Email: sunh15@163.com Email: jkliu@mail.kib.ac.cn
Yue Jiang

^aSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, P. R. of China Email: sunh15@163.com Email: jkliu@mail.kib.ac.cn
Xiao-Bao Li

^bDepartment of Civil and Environmental Engineering, Northwestern University, Evanston, IL, 60060, USA
Zheng-Hui Li

^aSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, P. R. of China Email: sunh15@163.com Email: jkliu@mail.kib.ac.cn
Huan Sun*

^aSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, P. R. of China Email: sunh15@163.com Email: jkliu@mail.kib.ac.cn
Ji-Kai Liu*

^aSchool of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, P. R. of China Email: sunh15@163.com Email: jkliu@mail.kib.ac.cn

Abstract

All articles of this category

Abstract

A convenient method was developed for direct regioselective fluorination of 8-aminoquinolines at the C-5 position by copper-catalyzed remote C–H activation using Selectfluor as the electrophile fluorinating reagent. With this method, diverse fluorinated quinoline derivatives were facilely obtained under mild conditions with moderate yields.

Key words

fluorination - copper-catalyzed - 8-aminoquinolines - Selectfluor - remote C–H activation

Full Text

References

References and Notes

1a Singh S. Kaur G. Mangla V. Gupta MK. J. Enzyme Inhib. Med. Chem. 2015; 30: 492
1b Michael JP. Nat. Prod. Rep. 2007; 24: 223

2 Hamer FM. J. Chem. Soc., Trans. 1921; 119: 1432

3a Adhikari S. Mandal S. Ghosh A. Das P. Das D. J. Org. Chem. 2015; 80: 8530
3b Niu W. Fan L. Nan M. Li Z. Lu D. Wong M. Shuang S. Dong C. Anal. Chem. 2015; 87: 2788

4a Kaur K. Jain M. Reddy RP. Jain R. Eur. J. Med. Chem. 2010; 45: 3245
4b Hussaini SM. A. Expert Opin. Ther. Pat. 2016; 26: 1201
4c Kumar S. Bawa S. Gupta H. Mini-Rev. Med. Chem. 2009; 9: 1648

5 Zaitsev VG. Shabashov D. Daugulis O. J. Am. Chem. Soc. 2005; 127: 13154
6 Sun H. Zhang Y. Chen P. Wu Y.-D. Zhang X. Huang Y. Adv. Synth. Catal. 2016; 358: 1946

For selected reviews, see:

7a Iwai T. Sawamura M. ACS Catal. 2015; 5: 5031
7b Prajapati SM. Patel KD. Vekariya RH. Panchal SN. Patel HD. RSC Adv. 2014; 4: 24463
7c Stephens DE. Larionov OV. Tetrahedron 2015; 71: 8683
7d Ramann GA. Cowen BJ. Molecules 2016; 21: 986

For represented examples, see:

8a Berman AM. Lewis JC. Bergman RG. Ellman JA. J. Am. Chem. Soc. 2008; 130: 14926
8b Wasa M. Worrell BT. Yu J.-Q. Angew. Chem. Int. Ed. 2010; 49: 1275
8c Chen Q. du Jourdin XM. Knochel P. J. Am. Chem. Soc. 2013; 135: 4958
8d Kwak J. Kim M. Chang S. J. Am. Chem. Soc. 2011; 133: 3780

9 Suess AM. Ertem MZ. Cramer CJ. Stahl SS. J. Am. Chem. Soc. 2013; 135: 9797

10a Xu J. Zhu X. Zhou G. Ying B. Ye P. Su L. Shen C. Zhang P. Org. Biomol. Chem. 2016; 14: 3016
10b Khan B. Kant R. Koley D. Adv. Synth. Catal. 2016; 358: 2352
10c Qiao H. Sun S. Yang F. Zhu Y. Kang J. Wu Y. Wu Y. Adv. Synth. Catal. 2017; 359: 1976

11 Whiteoak CJ. Planas O. Company A. Ribas X. Adv. Synth. Catal. 2016; 358: 1679
12 Liang HW. Jiang K. Ding W. Yuan Y. Shuai L. Chen YC. Wei Y. Chem. Commun. 2015; 51: 16928
13 Dou YD. Xie ZD. Shen C. Zhang PF. Zhu Q. ChemCatChem 2016; 8: 3570
14 Du C. Li P.-X. Zhu X. Suo J.-F. Niu J.-L. Song M.-P. Angew. Chem. Int. Ed. 2016; 55: 13571
15 Sun MM. Sun SY. Qiao HJ. Yang F. Zhu Y. Kang JX. Wu YS. Wu YJ. Org. Chem. Front. 2016; 3: 1646

16a Schlosser M. Angew. Chem. Int. Ed. 2006; 45: 5432
16b Wang J. Sánchez-Roselló M. Aceña JL. Pozo C. Sorochinsky AE. Fustero S. Soloshonok VA. Liu H. Chem. Rev. 2014; 114: 2432
16c Furuya T. Kamlet AS. Ritter T. Nature 2011; 473: 470

17a Chu L. Qing F.-L. Acc. Chem. Res. 2014; 47: 1513
17b Watson DA. Su M. Teverovskiy G. Zhang Y. Garcia-Fortanet J. Kinzel T. Buchwald SL. Science 2009; 325: 1661

For selected examples, see:

18a Grushin VV. Acc. Chem. Res. 2010; 43: 160
18b Li Y. Wu Y. Li S.-G. Wang X.-S. Adv. Synth. Catal. 2014; 356: 1412
18c Furuya T. Ritter T. J. Am. Chem. Soc. 2008; 130: 10060
18d Wang X. Mei T.-S. Yu J.-Q. J. Am. Chem. Soc. 2009; 131: 7520

19a Kuninobu Y. Nishi M. Kanai M. Org. Biomol. Chem. 2016; 14: 8092
19b 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
19c Jin L.-K. Lu G.-P. Cai C. Org. Chem. Front. 2016; 3: 1309
19d Shen C. Xu J. Ying B. Zhang P. ChemCatChem 2016; 8: 3560

20a Chen H. Li PH. Wang M. Wang L. Org. Lett. 2016; 18: 4794
20b Xu J. Qiao L. Ying B. Zhu X. Shen C. Zhang P. Org. Chem. Front. 2017; 4: 1116
20c Arockiam P. Guillemard L. Adv. Synth. Catal. 2017; 359: 2571

21 Ding J. Zhang Y. Li J. Org. Chem. Front. 2017; 4: 1528
22 Fluorinated Product 2a–t, General Procedure 8-Aminoquinoline derivatives 1 (0.1 mmol, 1.0 equiv), Cu(OAc)₂ (0.02 mmol, 0.2 equiv), Selectfluor (0.15 mmol, 1.5 equiv), KH₂PO₄ (0.2 mmol, 2.0 equiv), and Na₂SO₄ (50 mg) were weighed into an oven-dried Schlenk tube, and MeOH (1 mL) was added. The reaction vessel was capped and vacuum-flushed with N₂ three times. The reaction was stirred under N₂ atmosphere at 80 °C, and the progress of the fluorination was monitored by TLC. Upon complete consumption of 1, the reaction was cooled to room temperature. Volatile solvent and reagents were removed by rotary evaporation, and the residue was purified by silica gel flash chromatography using PE/EtOAc (100:1 to 20:1) to afford fluorinated product 2. N-(5-Fluoroquinolin-8-yl)-4-methylbenzamide (2a) 45% yield, white solid. ¹H NMR (600 MHz, chloroform-d): δ = 10.52 (s, 1 H), 8.94–8.85 (m, 2 H), 8.47 (dd, J = 8.4, 1.7 Hz, 1 H), 8.01–7.94 (m, 2 H), 7.56 (dd, J = 8.4, 4.2 Hz, 1 H), 7.40–7.33 (m, 2 H), 7.30–7.27 (m, 1 H), 2.46 (s, 3 H). ¹³C NMR (151 MHz, chloroform-d): δ = 165.48 , 153.87 (d, J = 250.7 Hz), 149.22, 142.55, 139.09 (d, J = 3.0 Hz), 132.28, 131.35 (d, J = 3.0 Hz), 129.98 (d, J = 3.0 Hz), 129.62, 127.37, 121.87 (d, J = 3.0 Hz), 119.00 (d, J = 3.0 Hz), 116.09 (d, J = 7.6 Hz), 110.72 (d, J = 19.6 Hz), 21.71. ¹⁹F NMR (565 MHz, chloroform-d): δ = –129.22. HRMS (ESI): m/z calcd for C₁₇H₁₄ON₂F [M + H]⁺: 281.1090; found: 281.1086. 4-Fluoro-N-(5-fluoroquinolin-8-yl)benzamide (2g) 38% yield, white solid. ¹H NMR (600 MHz, chloroform-d): δ = 10.50 (s, 1 H), 8.91 (dd, J = 4.2, 1.6 Hz, 1 H), 8.87 (dd, J = 8.6, 5.3 Hz, 1 H), 8.48 (dd, J = 8.4, 1.7 Hz, 1 H), 8.12–8.06 (m, 2 H), 7.57 (dd, J = 8.4, 4.2 Hz, 1 H), 7.30–7.23 (m, 3 H). ¹³C NMR (151 MHz, chloroform-d): δ = 165.83, 164.23, 164.16, 153.89 (d, J = 252.2 Hz), 149.16, 138.92 (d, J = 3.0 Hz), 131.16 (d, J = 3.0 Hz), 130.96 (d, J = 4.5 Hz), 129.95 (d, J = 4.5 Hz), 129.64 (d, J = 9.1 Hz), 121.82 (d, J = 1.5 Hz), 118.90 (d, J = 18.1 Hz), 116.07 (d, J = 9.1 Hz), 115.97 (d, J = 22.6 Hz), 110.59 (d, J = 19.6 Hz). ¹⁹F NMR (565 MHz, chloroform-d): δ = –107.51, –128.74. HRMS (ESI): m/z calcd for C₁₆H₁₁ON₂F₂ [M + H]⁺: 285.0839; found: 285.0833. N-(5-Fluoroquinolin-8-yl)-2,6-dimethoxybenzamide (2i) 34% yield, white solid. ¹H NMR (600 MHz, chloroform-d): δ = 10.10 (s, 1 H), 8.99 (dd, J = 7.6, 1.3 Hz, 1 H), 8.78 (dd, J = 4.2, 1.7 Hz, 1 H), 8.18 (dd, J = 8.2, 1.7 Hz, 1 H), 7.61 (t, J = 7.9 Hz, 1 H), 7.56 (dd, J = 8.3, 1.4 Hz, 1 H), 7.45 (dd, J = 8.2, 4.2 Hz, 1 H), 7.14 (dd, J = 11.2, 9.1 Hz, 1 H), 6.64 (dd, J = 9.2, 3.3 Hz, 1 H), 4.01 (d, J = 1.9 Hz, 3 H), 3.83 (s, 3 H). ¹³C NMR (151 MHz, chloroform-d): δ = 162.92 (d, J = 3.0 Hz), 153.18 (d, J = 3.0 Hz), 150.80 (d, J = 241.6 Hz), 148.35, 145.77 (d, J = 12.1 Hz) 138.60, 136.44, 134.76, 128.10, 127.60, 121.97, 121.73, 117.79 (d, J = 21.1 Hz), 117.01, 106.10 (d, J = 7.6 Hz), 62.32 (d, J = 4.5 Hz), 56.49. ¹⁹F NMR (565 MHz, chloroform-d): δ = –139.30, –139.33. HRMS (ESI): m/z calcd for C₁₈H₁₆O₃N₂F [M + H]⁺: 327.1145; found: 327.1140. 2,3,4,5,6-Pentafluoro-N-(5-fluoroquinolin-8-yl)benzamide (2j) 23% yield, white solid. ¹H NMR (600 MHz, chloroform-d): δ = 10.19 (s, 1 H), 8.87 (ddd, J = 4.7, 3.0, 1.7 Hz, 1 H), 8.83 (ddd, J = 8.9, 5.3, 3.8 Hz, 1 H), 8.48 (ddd, J = 8.4, 4.2, 1.7 Hz, 1 H), 7.58 (ddd, J = 8.5, 4.2, 2.9 Hz, 1 H), 7.32–7.27 (m, 1 H). ¹³C NMR (151 MHz, chloroform-d): δ = 155.23, 154.61 (d, J = 253.7 Hz), 149.49, 145.35 (m), 143.66 (m), 141.81 (m), 138.65 (m), 136.98 (m), 130.07 (m), 122.08, 118.90 (dd, J = 18.4, 3.6 Hz), 116.99 (d, J = 9.1 Hz), 116.94 (m), 110.51(dd, J = 19.6, 2.8 Hz). ¹⁹F NMR (565 MHz, chloroform-d): δ = –126.79, –139.92 (d, J = 19.0 Hz), –149.94 (d, J = 20.9 Hz), –149.99, –159.64 (t, J = 19.2 Hz). HRMS (ESI): m/z calcd for C₁₆H₇ON₂F₆ [M + H]⁺: 357.0463; found: 357.0457.

Supplementary Material

Supporting Information (PDF) (opens in new window)

Primary Data

Primary Data (ZIP) (opens in new window)