Chemoselective Electrochemical Oxidation of Secondary Alcohols Using a Recyclable Chloride-Based Mediator

Abstract

Selective anodic oxidation of alcohols in the presence of other functional groups can be accomplished by using nitroxyl radical mediators. However, the electrochemical chemoselective oxidation of secondary alcohols in the presence of primary alcohols is an unsolved issue. Herein, we report an electrochemical procedure for the selective oxidation of secondary alcohols by using an inexpensive chloride salt that acts as a redox mediator and supporting electrolyte. The method is based on the controlled anodic generation of active chlorine species, which selectively oxidize secondary alcohols to the corresponding ketones when primary hydroxy groups are present. The method has been demonstrated for a variety of substrates. The corresponding ketones were obtained in good to excellent yields. Moreover, the chloride salt can be easily recovered by a simple extraction procedure for reuse, rendering the method highly sustainable.

Key words

electroorganic synthesis - alcohols - oxidation - redox mediators - anodic oxidation - sustainability

Publication History

Received: 30 March 2021

Accepted after revision: 19 May 2021

Accepted Manuscript online:
19 May 2021

Article published online:
02 June 2021

• References and Notes

• 1 Caron S, Dugger RW, Ruggeri SG, Ragan JA, Brown Ripin DH. Chem. Rev. 2006; 106: 2943
• 2a Cohen MD, Kargacin B, Klein CB, Costa M. Crit. Rev. Toxicol. 1993; 23: 255
• 2b Shekhawat K, Chatterjee S, Joshi B. Int. J. Adv. Res. 2015; 3: 167
• 3 Tidwell TT. Synthesis 1990; 857
• 4a Beejapur HA, Zhang Q, Hu K, Zhu L, Wang J, Ye Z. ACS Catal. 2019; 9: 2777
• 4b de Nooy AE. J, Besemer AC, van Bekkum H. Synthesis 1996; 1153
• 4c Ciriminna R, Pagliaro M. Org. Process Res. Dev. 2010; 14: 245
• 5a Nutting JE, Rafiee M, Stahl SS. Chem. Rev. 2018; 118: 4834
• 5b Ciriminna R, Ghahremani M, Karimi B, Pagliaro M. ChemistryOpen 2017; 6: 5
• 6 Semmelhack MF, Chou CS, Cortes DA. J. Am. Chem. Soc. 1983; 105: 4492
• 7 Francke R, Little RD. Chem. Soc. Rev. 2014; 43: 2492
• 8 Yoshida J.-i, Nakai R, Kawabata N. J. Org. Chem. 1980; 45: 5269
• 9 Shono T, Matsumura Y, Hayashi J, Mizoguchi M. Tetrahedron Lett. 1979; 20: 165
• 10 Leonard JE, Scholl PC, Steckel TP, Lentsch SE, Van De Mark MR. Tetrahedron Lett. 1980; 21: 4695
• 11 Bender MT, Lam YC, Hammes-Schiffer S, Choi K.-S. J. Am. Chem. Soc. 2020; 142: 21538
• 12a Demizu Y, Shiigi H, Oda T, Matsumura Y, Onomura O. Tetrahedron Lett. 2008; 49: 48
• 12b Kuroboshi M, Yoshihisa H, Cortona MN, Kawakami Y, Gao Z, Tanaka H. Tetrahedron Lett. 2000; 41: 8131
• 13 Tojo G, Fernández M. Oxidation of Alcohols to Aldehydes and Ketones: A Guide to Current Common Practice. Springer Science; New York: 2006
• 14 Goehring RR. In Encyclopedia of Reagents for Organic Synthesis . Wiley; Chichester: 2001.
• 15 Wicha J, Zarecki A. Tetrahedron Lett. 1974; 3059

Basic pH values favor TEMPO-mediated alcohol oxidations; see:
• 16a Hill-Cousins JT, Kuleshova J, Green RA, Birkin PR, Pletcher D, Underwood TJ, Leach SG, Brown RC. D. ChemSusChem 2012; 5: 326
• 16b Sommer F, Kappe CO, Cantillo D. Chem. Eur. J. 2021; 27: 6044
• 17 Stevens RV, Chapman KT, Stubbs CA, Tam WW, Albizati KF. Tetrahedron Lett. 1982; 23: 4647
• 18 3-(Hydroxymethyl)heptan-4-one (2a); Typical Procedure A 5 mL IKA ElectraSyn 2.0 vial (undivided cell) equipped with a stirrer bar was charged with Me₄NCl (164 mg, 1.5 mmol) and MeCN (3 mL). Diol 1a (0.6 mmol), H₂O (75 μL), and AcOH (86 μL) were added, and the vial was capped with a cell head equipped with a standard IKA ElectraSyn graphite anode and a stainless-steel cathode. The mixture was stirred until all the supporting electrolyte was dissolved and then a constant current of 5 mA was applied, with stirring at 1000 rpm. After 4.5 F/mol of charge had been passed, the mixture was evaporated under reduced pressure. The residue was treated with aq NaHCO₃ and extracted with CH₂Cl₂. The organic phase was dried (Na₂SO₄) and concentrated under reduced pressure to give a pale-yellow oil; yield: 82 mg (95%).
• 19 H NMR (300 MHz, CDCl₃): δ = 3.82 (dd, J = 11.1, 7.3 Hz, 1 H), 3.72 (dd, J = 11.1, 4.0 Hz, 1 H), 2.69–2.61 (m, 1 H), 2.49 (t, J = 14.6 Hz, 2 H), 1.76–1.36 (m, 4 H), 0.98–0.92 (m, 6 H). MS (EI): m/z (%) = 55 (100), 56 (60), 57 (11), 71 (73), 73 (10), 83 (27), 89 (60), 97 (8), 114 (5).
• 20 Sakai A, Hendrickson DG, Hendrickson WH. Tetrahedron Lett. 2000; 41: 2759
• 21a Stevens RV, Chapman KT, Weller HN. J. Org. Chem. 1980; 45: 2030
• 21b Güclü D, Rale M, Fessner W.-D. Eur. J. Org. Chem. 2015; 2960
• 21c Chen F.-F, Cosgrove SC, Birmingham WR, Mangas-Sanchez J, Citoler J, Thompson MP, Zheng G.-W, Xu J.-H, Turner NJ. ACS Catal. 2019; 9: 11813