Direct Electrochemical C(sp3)–H Amidation Enabled by Hexafluoroisopropanol (HFIP)

Fengyi Li; Ke Liu; Qi Sun; Sheng Zhang; Man-Bo Li

doi:10.1055/a-2176-1840

SynOpen, Table of Contents

CC BY 4.0 · SynOpen 2023; 07(04): 491-495
DOI: 10.1055/a-2176-1840

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Virtual Collection Electrochemical Organic Synthesis

Direct Electrochemical C(sp³)–H Amidation Enabled by Hexafluoroisopropanol (HFIP)

Fengyi Li‡

^aInstitutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, P. R. of China

,

Ke Liu‡

^aInstitutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, P. R. of China

,

Qi Sun

^bHefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230026, P. R. of China

,

Sheng Zhang∗

^aInstitutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, P. R. of China

,

Man-Bo Li∗

^aInstitutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, P. R. of China

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Abstract

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Abstract

A direct electrochemical amidation of xanthene was readily achieved under direct anodic oxidation. The reactivity of benzamides was significantly enhanced by the virtue of the solvent effect of hexafluoroisopropanol (HFIP). An obvious hydrogen bonding between HFIP and benzamide was detected, and the proton-coupled electron-transfer (PCET) effect was proposed for the enhancement effect of HFIP. In this transformation, a broad range of primary and secondary amides were readily used as amidating reagents, including l-proline-, naproxen-, and probencid-derived amides. We proposed a plausible reaction mechanism for this direct amidation based on the experimental observations.

Key words

electrochemical amidation - C(sp³)–H - hexafluoroisopropanol

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References

References and Notes
1 Ertl P, Altmann E, McKenna JM. J. Med. Chem. 2020; 63: 8408

For the synthesis of amides, see:

2a Montalbetti CA. G. N, Falque V. Tetrahedron 2005; 61: 10827
2b Ojeda-Porras A, Gamba-Sánchez D. J. Org. Chem. 2016; 81: 11548
2c Pattabiraman VR, Bode JW. Nature 2011; 480: 471

For the approaches involving C(sp³)–H activation, see:

3a Wang H, Tang G, Li X. Angew. Chem. Int. Ed. 2015; 54: 13049
3b Tan PW, Mak AM, Sullivan MB, Dixon DJ, Seayad J. Angew. Chem. Int. Ed. 2017; 56: 16550
3c Antien K, Geraci A, Parmentier M, Baudoin O. Angew. Chem. Int. Ed. 2021; 60: 22948

For the approaches involving nitrene insertion, see:

4a Knecht T, Mondal S, Ye J.-H, Das M, Glorius F. Angew. Chem. Int. Ed. 2019; 58: 7117
4b Burman JS, Harris RJ, Farr CM. B, Bacsa J, Blakey SB. ACS Catal. 2019; 9: 5474
4c Lei H, Rovis T. J. Am. Chem. Soc. 2019; 141: 2268
4d Tang J.-J, Yu X, Wang Y, Yamamoto Y, Bao M. Angew. Chem. Int. Ed. 2021; 60: 16426
4e Bakhoda A, Jiang Q, Badiei YM, Bertke JA, Cundari TR, Warren TH. Angew. Chem. Int. Ed. 2019; 58: 3421

5a Breugst M, Tokuyasu T, Mayr H. J. Org. Chem. 2010; 75: 5250
5b Kütt A, Tshepelevitsh S, Saame J, Lõkov M, Kaljurand I, Selberg S, Leito I. Eur. J. Org. Chem. 2021; 1407

For reviews of synthetic electrochemistry, see:

6a Francke R, Little RD. Chem. Soc. Rev. 2014; 43: 2492
6b Yan M, Kawamata Y, Baran PS. Chem. Rev. 2017; 117: 13230
6c Jiang Y, Xu K, Zeng C.-C. Chem. Rev. 2018; 118: 4485
6d Yoshida J.-i, Shimizu A, Hayashi R. Chem. Rev. 2018; 118: 4702
6e Moeller KD. Chem. Rev. 2018; 118: 4817
6f Waldvogel SR, Lips S, Selt M, Riehl B, Kampf CJ. Chem. Rev. 2018; 118: 6706
6g Yuan Y, Lei A. Acc. Chem. Res. 2019; 52: 3309
6h Xiong P, Xu H.-C. Acc. Chem. Res. 2019; 52: 3339
6i Jiao K.-J, Xing Y.-K, Yang Q.-L, Qiu H, Mei T.-S. Acc. Chem. Res. 2020; 53: 300
6j Gandeepan P, Finger LH, Meyer TH, Ackermann L. Chem. Soc. Rev. 2020; 49: 4254
6k Novaes LF. T, Liu J, Shen Y, Lu L, Meinhardt JM, Lin S. Chem. Soc. Rev. 2021; 50: 7941
6l Cheng X, Lei A, Mei T.-S, Xu H.-C, Xu K, Zeng C. CCS Chem. 2022; 4: 1120

7 Hu X, Zhang G, Nie L, Kong T, Lei A. Nat. Commun. 2019; 10: 5467
8 Hou Z.-W, Liu D.-J, Xiong P, Lai X.-L, Song J, Xu H.-C. Angew. Chem. Int. Ed. 2021; 60: 2943
9 Wang Y, Lin Z, Oliverira JC. A, Ackermann L. J. Org. Chem. 2021; 86: 15935
10 Li F, Liang Y, Zhan X, Zhang S, Li M.-B. Org. Chem. Front. 2022; 9: 5571

11a Zhang S, Li L, Zhang J, Zhang J, Xue M, Xu K. Chem. Sci. 2019; 10: 3181
11b Zhang S, Li L, Li J, Shi J, Xu K, Gao W, Zong L, Li G, Findlater M. Angew. Chem. Int. Ed. 2021; 60: 7275
11c Zhang S, Shi J, Li J, Li M.-B, Li G, Findlater M. CCS Chem. 2022; 4: 1938
11d Liang Y, Zhan X, Li F, Bi H, Fan W, Zhang S, Li M.-B. Chem. Catal. 2023; 3: 100582
11e Zhang S, Liang Y, Liu K, Zhan X, Fan W, Li M.-B, Findlater M. J. Am. Chem. Soc. 2023; 145: 14143
11f Zhang S, Findlater M. ACS Catal. 2023; 13: 8731

12 Colomer I, Chamberlain AE. R, Haughey MB, Donohoe TJ. Nat. Rev. Chem. 2017; 1: 0088
13 Murray PR. D, Cox JH, Chiappini ND, Roos CB, McLoughlin EA, Hejna BG, Nguyen ST, Ripberger HH, Ganley JM, Tsui E, Shin NY, Koronkiewicz B, Qiu G, Knowles RR. Chem. Rev. 2022; 122: 2017

For bioactive xanthene, see:

14a Luo L, Jia B.-Z, Wei X.-Q, Xiao Z.-L, Wang H, Sun Y.-M, Shen Y.-D, Lei H.-T, Xu Z.-L. Sens. Actuators, B 2021; 332: 129561
14b Park I.-S, Seo HR, Kim K, Lee H, Shum D, Choi I, Kim J. Biochem. Biophys. Res. Commun. 2020; 527: 709
14c Watterson KR, Hansen SV. F, Hudson BD, Alvarez-Curto E, Raihan SZ, Azevedo CM. G, Martin G, Dunlop J, Yarwood SJ, Ulven T, Milligan G. Mol. Pharmacol. 2017; 91: 630

15 General Procedure for the Electrochemical Amidation (3a as an Example) An undivided cell was equipped with a magnet stirrer, platinum plate (1.5 × 1.5 cm²), and graphite rod (0.6 × 10 cm), as anode and cathode, respectively (the electrolysis setup is shown in Figure S1). Substrate benzamide (1a, 61 mg, 0.5 mmol), 9H-xanthene (2a, 137 mg, 0.75 mmol), and n-Bu₄NClO₄ (342 mg, 1 mmol) were added to the solvent MeCN/HFIP (9/1 mL). The resulting mixture was allowed to stir and electrolyze under constant current conditions (15 mA) at room temperature for 3 h. The reaction mixture was condensed with a rotary evaporator. The residue was purified by column chromatography (PE/EtOAc = 20/1 to10/1, V/V) on silica gel to afford the desired product 3a (149 mg) in 99% yield. N-(9H-Xanthen-9-yl)benzamide (3a) 149 mg, 99% yield; white solid, mp 227–228 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.78 (d, J = 8.0 Hz, 2 H), 7.57 (d, J = 8.0 Hz, 2 H), 7.50 (t, J = 8.0 Hz, 1 H), 7.42 (t, J = 8.0 Hz, 2 H), 7.33 (t, J = 8.0 Hz, 2 H), 7.16–7.10 (m, 4 H), 6.78 (d, J = 12.0 Hz, 1 H), 6.61 (d, J = 8.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 166.5, 151.1, 134.0, 131.8, 129.7, 129.4, 128.6, 127.0, 123.7, 121.0, 116.7, 44.3.

16a Lin M.-Y, Xu K, Jiang Y.-Y, Liu Y.-G, Sun B.-G, Zeng C.-C. Adv. Synth. Catal. 2018; 360: 1665
16b Yang Y.-Z, Song R.-J, Li J.-H. Org. Lett. 2019; 21: 3228
16c Wei B, Qin J.-H, Yang Y.-Z, Xie Y.-X, Ouyang X.-H, Song R.-J. Org. Chem. Front. 2022; 9: 816
16d Chen X, Liu H, Gao H, Li P, Miao T, Li H. J. Org. Chem. 2022; 87: 1056

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