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Synlett 2020; 31(19): 1894-1898
DOI: 10.1055/s-0040-1707141
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© Georg Thieme Verlag Stuttgart · New York

Accelerating Electrochemical Synthesis through Automated Flow: Efficient Synthesis of Chalcogenophosphites

Nasser Amri
,
Thomas Wirth∗
Support from Cardiff University and from the Chemistry Department, Jazan University, Saudi Arabia, are appreciated.
Further Information

Publication History

Received: 11 May 2020

Accepted after revision: 17 May 2020

Publication Date:
16 June 2020 (online)

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Published as part of the Cluster Integrated Synthesis Using Continuous-Flow Technologies

Abstract

Integrated electrochemical reactors in automated flow systems have been utilised for chalcogenophosphite formations. Multiple electrochemical reactions can be performed using a programmed sequence in a fully autonomous way. Differently functionalised chalcogenophosphites have been efficiently synthesised in short reaction times.

Key words

automated synthesis - electrolysis - flow microreactors - phosphites - selenium - sulfur

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707141.
  • Supporting Information
 

  • References and Notes

    • 3a Kawaguchi SI, Kotani M, Atobe S, Nomoto A, Sonoda M, Ogawa A. Organometallics 2011; 30: 6766
      Crossref
    • 3b Wang J, Wang X, Li H, Yan J. J. Organomet. Chem. 2018; 859: 75
      Crossref
    • 3c Zhang X, Shi Z, Shao C, Zhao J, Wang D, Zhang G, Li L. Eur. J. Org. Chem. 2017; 1884
    • 3d Choudhary R, Singh P, Bai R, Sharma MC, Badsara SS. Org. Biomol. Chem. 2019; 17: 9757
      CrossrefPubMed
    • 3e Zhu Y, Chen T, Li S, Shimada S, Han LB. J. Am. Chem. Soc. 2016; 138: 5825
      CrossrefPubMed
  • 4 Li CY, Liu YC, Li YX, Reddy DM, Lee CF. Org. Lett. 2019; 21: 7833
    CrossrefPubMed
  • 5 Deng L, Wang Y, Mei H, Pan Y, Han J. J. Org. Chem. 2019; 84: 949
    CrossrefPubMed
  • 6 Guo S, Li S, Zhang Z, Yan W, Cai H. Tetrahedron Lett. 2020; 61: 151566
    CrossrefPubMed
  • 7 Wang Y, Qian P, Su JH, Li Y, Bi M, Zha Z, Wang Z. Green Chem. 2017; 19: 4769
    Crossref
  • 8 Dong X, Wang R, Jin W, Liu C. Org. Lett. 2020; 22: 3062
    CrossrefPubMed
  • 9 Fu N, Song L, Liu J, Shen Y, Siu JC, Lin S. J. Am. Chem. Soc. 2019; 141: 14480
    CrossrefPubMed
    • 10a Jamison TF, Koch G. Flow Chemistry in Organic Synthesis . Thieme; Stuttgart: 2018
      Google Scholar
    • 10b Wirth T. Microreactors in Organic Chemistry and Catalysis, 2nd ed. Wiley-VCH; Weinheim: 2013
      Google Scholar
    • 10c Yoshida J. Flash Chemistry: Fast Organic Synthesis in Microsystems. Wiley-VCH; Weinheim: 2008
      Google Scholar
    • 11a Elsherbini M, Wirth T. Acc. Chem. Res. 2019; 52: 3287
      CrossrefPubMed
    • 11b Folgueiras-Amador AA, Wirth T. In Flow Chemistry in Organic Synthesis . Jamison TF, Koch G. Thieme; Stuttgart: 2018
      Google Scholar
    • 11c Pletcher D, Green RA, Brown RC. D. Chem. Rev. 2018; 118: 4573
      CrossrefPubMed
    • 11d Atobe M, Tateno H, Matsumura Y. Chem. Rev. 2018; 118: 4541
      CrossrefPubMed
    • 11e Wiebe A, Gieshoff T, Möhle S, Rodrigo E, Zirbes M, Waldvogel SR. Angew. Chem. Int. Ed. 2018; 57: 5594
      CrossrefPubMed
  • 12 Amri N, Wirth T. Synthesis 2020; 52: 1751
    Article in Thieme Connect
  • 13 Experimental Conditions The electrolysis was performed in an undivided cell using a Vapourtec ion electrochemical flow reactor (reactor volume = 0.6 mL, spacer 0.5 mm) using a graphite (Gr) anode and a platinum (Pt) cathode (surface area: A = 12 cm2). A solution of phosphite (0.2 M in CH3CN) is placed in vial A and a mixture of diphenyl diselenide (0.05 M) and Et4NCl (0.01 M) in CH3CN placed in vial B. Each solution was injected to 8 mL sample loop. The reactor temperature was set at 25 °C with a flow rate of 1.2 mL min–1, and the current was set to 96 mA which switched on automatically. Then, both solutions were pumped into a PTFE coil (1 mm internal diameter) and mixed via a T-piece connected to a 30 cm PTFE coil before the inlet of the electrochemical rector. After reaching a steady state, the solution (12 mL) was collected at the reactor outlet automatically into a collection glass vial. The solvent was removed under vacuum. The crude product was purified by column chromatography (EtOAc/cyclohexane).
  • 14 Characterisation Data O,O-Diethyl Se-Phenyl Phosphoroselenoate (3a) 56 mg (89% yield). 1H NMR (500 MHz, CDCl3): δ = 7.69–7.60 (m, 2 H), 7.38–7.29 (m, 3 H), 4.25–4.11 (m, 4 H), 1.30 (td, J = 7.1, 0.8 Hz, 6 H). 13C NMR (126 MHz, CDCl3): δ = 135.7 (d, J = 3.7 Hz), 129.6 (d, J = 1.3 Hz), 128.9 (d, J = 2.5 Hz), 123.9 (d, J = 8.7 Hz), 64.0 (d, J = 6.2 Hz), 16.05 (d, J = 7.5 Hz). 31P NMR (202 MHz, CDCl3): δ = 17.9. O,O-Dimethyl Se-Phenyl Phosphoroselenoate (3b) 123 mg (77% yield). 1H NMR (500 MHz, CDCl3): δ = 7.68–7.58 (m, 2 H), 7.39–7.29 (m, 3 H), 3.81 (s, 3 H), 3.78 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 135.7 (d, J = 3.7 Hz), 129.7 (d, J = 2.5 Hz), 129.1 (d, J = 2.5 Hz), 123.4 (d, J = 8.7 Hz), 54.2 (d, J = 6.2 Hz). 31P NMR (202 MHz, CDCl3): δ = 21.9. O,O-Dibutyl Se-Phenyl Phosphoroselenoate (3c) 188 mg (90% yield). 1H NMR (500 MHz, CDCl3): δ = 7.66–7.62 (m, 2 H), 7.37–7.27 (m, 3 H), 4.18–4.02 (m, 4 H), 1.66–1.59 (m, 4 H), 1.42–1.34 (m, 4 H), 0.89 (t, J = 7.4 Hz, 6 H). 13C NMR (126 MHz, CDCl3): δ = 135.6 (d, J = 4.7 Hz), 129.5 (d, J = 2.0 Hz), 128.8 (d, J = 2.5 Hz), 124.0 (d, J = 8.4 Hz), 67.7 (d, J = 6.4 Hz), 32.2 (d, J = 7.3 Hz), 18.8, 13.7. 31P NMR (202 MHz, CDCl3): δ = 18.0. O,O-Diisopropyl Se-Phenyl Phosphoroselenoate (3d) 168 mg (87% yield). 1H NMR (500 MHz, CDCl3): δ = 7.71–7.62 (m, 2 H), 7.35–7.27 (m, 3 H), 4.84–4.73 (m, 2 H), 1.33 (d, J = 6.2 Hz, 6 H), 1.25 (d, J = 6.2 Hz, 6 H). 13C NMR (126 MHz, CDCl3): δ = 135.3 (d, J = 4.9 Hz), 129.4 (d, J = 1.8 Hz), 128.6 (d, J = 2.3 Hz), 124.7 (d, J = 8.3 Hz), 73.2 (d, J = 6.6 Hz), 24.0 (d, J = 3.8 Hz), 23.6 (d, J = 6.0 Hz). 31P NMR (202 MHz, CDCl3): δ = 14.6. O,O-Bis(2-ethylhexyl) Se-Phenyl Phosphoroselenoate (3e) 218 mg (79% yield). 1H NMR (500 MHz, CDCl3): δ = 7.70–7.60 (m, 2 H), 7.37–7.26 (m, 3 H), 4.08–3.92 (m, 4 H), 1.59–1.47 (m, 2 H), 1.36–1.19 (m, 16 H), 0.91–0.81 (m, 12 H). 13C NMR (126 MHz, CDCl3): δ = 135.6 (dt, J = 4.7, 1.8 Hz), 129.5 (d, J = 1.9 Hz), 128.7 (d, J = 2.3 Hz), 124.0 (d, J = 8.4 Hz), 70.0 (dd, J = 7.6, 2.1 Hz), 40.1 (d, J = 1.2 Hz), 30.0 (d, J = 6.9 Hz), 28.9 (d, J = 2.2 Hz), 23.4 (d, J = 5.6 Hz), 23.0, 14.1, 11.0. 31P NMR (202 MHz, CDCl3): δ = 17.8. O,O-Dibenzyl Se-Phenyl Phosphoroselenoate (3f) 211 mg (84% yield). 1H NMR (500 MHz, CDCl3): δ = 7.59–7.53 (m, 2 H), 7.36–7.30 (m, 7 H), 7.29–7.22 (m, 6 H), 5.12 (qd, J = 11.7, 8.7 Hz, 4 H). 13C NMR (126 MHz, CDCl3): δ = 136.0 (d, J = 4.7 Hz), 135.5 (d, J = 7.9 Hz), 129.7 (d, J = 2.2 Hz), 129.1 (d, J = 2.6 Hz), 128.7, 128.6, 128.3, 123.5 (d, J = 8.6 Hz), 69.3 (d, J = 6.1 Hz). 31P NMR (202 MHz, CDCl3): δ = 18.5. 5,5-Dimethyl-2-(phenylselanyl)-1,3,2-dioxaphosphinane 2-Oxide (3g) 154 mg (84% yield). 1H NMR (500 MHz, CDCl3): δ = 7.76–7.72 (m, 2 H), 7.39–7.30 (m, 3 H), 4.15 (dd, J = 10.6, 4.3 Hz, 2 H), 3.87 (ddt, J = 24.7, 11.4, 1.6 Hz, 2 H), 1.28 (s, 3 H), 0.86 (s, 3 H). 13C NMR (126 MHz, CDCl3): δ = 136.0 (d, J = 4.7 Hz), 129.8 (d, J = 2.0 Hz), 129.2 (d, J = 2.5 Hz), 122.0 (d, J = 8.0 Hz), 78.2 (d, J = 7.3 Hz), 32.7 (d, J = 7.0 Hz), 22.3, 20.6 (d, J = 1.0 Hz). 31P NMR (202 MHz, CDCl3): δ = 9.7. O,O,Se-Triphenyl Phosphoroselenoate (3h) 154 mg (95% yield). 1H NMR (500 MHz, CDCl3): δ = 7.62–7.40 (m, 2 H), 7.35–7.25 (m, 7 H), 7.20–7.16 (m, 6 H). 13C NMR (126 MHz, CDCl3): δ = 150.3 (d, J = 8.6 Hz), 136.3 (d, J = 4.8 Hz), 129.8 (d, J = 1.0 Hz), 129.6 (d, J = 2.5 Hz), 129.4 (d, J = 3.0 Hz), 125.7 (d, J = 1.5 Hz), 122.7 (d, J = 9.1 Hz), 120.7 (d, J = 5.1 Hz). 31P NMR (202 MHz, CDCl3): δ = 9.4. Se-Phenyl Diphenylphosphinoselenoate (3i) 198 mg (92% yield). 1H NMR (500 MHz, CDCl3): δ = 7.87–7.77 (m, 4 H), 7.53–7.46 (m, 4 H), 7.46–7.41 (m, 4 H), 7.26–7.23 (m, 1 H), 7.19–7.12 (m, 2 H). 13C NMR (126 MHz, CDCl3): δ = 136.4 (d, J = 3.3 Hz), 134.0 (s), 133.3 (s), 132.4 (d, J = 3.1 Hz), 131.5 (d, J = 10.6 Hz), 129.4 (d, J = 1.6 Hz), 128.8 (d, J = 2.0 Hz), 128.6 (d, J = 13.2 Hz), 123.9 (d, J = 5.7 Hz). 31P NMR (202 MHz, CDCl3): δ = 20.2. Se-Phenyl Di-p-tolylphosphinoselenoate (3j) 204 mg (88% yield). 1H NMR (500 MHz, CDCl3): δ = 7.73–7.66 (m, 4 H), 7.52–7.46 (m, 2 H), 7.25–7.19 (m, 5 H), 7.18–7.13 (m, 2 H), 2.37 (s, 6 H). 13C NMR (126 MHz, CDCl3): δ = 142.9 (d, J = 3.1 Hz), 136.4 (d, J = 3.3 Hz), 131.5 (d, J = 11.0 Hz), 131.1, 130.3, 129.42 (d, J = 13.6 Hz), 129.40 (d, J = 1.5 Hz), 128.7 (d, J = 1.9 Hz), 124.5 (d, J = 5.6 Hz), 21.8. 31P NMR (202 MHz, CDCl3): δ = 40.2. Se-Phenyl Bis(3,5-dimethylphenyl)phosphinoselenoate (3k) 212 mg (85% yield). 1H NMR (500 MHz, CDCl3): δ = 7.53–7.48 (m, 2 H), 7.45–7.37 (m, 4 H), 7.26–7.22 (m, 1 H), 7.19–7.14 (m, 2 H), 7.12–7.07 (m, 2 H), 2.30 (s, 12 H). 13C NMR (126 MHz, CDCl3): δ = 138.2 (d, J = 13.9 Hz), 136.4 (d, J = 3.2 Hz), 134.0 (d, J = 3.2 Hz), 133.0, 129.2 (d, J = 1.5 Hz), 128.9 (d, J = 10.5 Hz), 128.7 (d, J = 1.9 Hz), 124.3 (d, J = 5.7 Hz), 21.3. 31P NMR (202 MHz, CDCl3): δ = 41.2. Se-Phenyl Di(naphthalen-2-yl)phosphinoselenoate (3l) 228 mg (83% yield). 1H NMR (500 MHz, CDCl3): δ = 8.45 (d, J = 15.0 Hz, 2 H), 7.93–7.82 (m, 8 H), 7.61–7.51 (m, 6 H), 7.22–7.15 (m, 1 H), 7.14–7.06 (m, 2 H). 13C NMR (126 MHz, CDCl3): δ = 136.4 (d, J = 3.2 Hz), 134.9 (d, J = 2.6 Hz), 133.7 (d, J = 9.6 Hz), 132.5 (d, J = 14.4 Hz), 131.0, 130.25, 129.4 (d, J = 1.5 Hz), 129.2, 128.8 (d, J = 1.9 Hz), 128.5 (d, J = 13.3 Hz), 127.9, 127.1, 126.1 (d, J = 12.1 Hz), 123.9 (d, J = 5.7 Hz). 31P NMR (202 MHz, CDCl3): δ = 39.8. O-Ethyl Se-Phenyl Phenylphosphonoselenoate (3m) 156 mg (80% yield). 1H NMR (500 MHz, CDCl3): δ = 7.54–7.47 (m, 2 H), 7.40–7.35 (m, 1 H), 7.28–7.16 (m, 5 H), 7.10–7.04 (m, 2 H), 4.32–4.18 (m, 2 H), 1.31 (t, J = 7.1 Hz, 3 H). 13C NMR (126 MHz, CDCl3): δ = 150.5 (d, J = 3.6 Hz), 133.4, 132.5 (d, J = 3.3 Hz), 132.3, 131.1 (d, J = 11.0 Hz), 129.3 (d, J = 2.1 Hz), 128.8 (d, J = 2.5 Hz), 128.2 (d, J = 14.9 Hz), 124.3 (d, J = 6.6 Hz), 62.7, 16.3. 31P NMR (202 MHz, CDCl3): δ = 38.4. 6-(Phenylselanyl)dibenzo[c,e][1,2]oxaphosphinine 6-Oxide (3n) 192 mg (86% yield). 1H NMR (500 MHz, CDCl3): δ = 7.90–7.83 (m, 1 H), 7.77–7.73 (m, 1 H), 7.66–7.60 (m, 2 H), 7.46 (tdd, J = 7.5, 3.6, 1.0 Hz, 1 H), 7.33–7.29 (m, 1 H), 7.25–7.20 (m, 2 H), 7.17–7.12 (m, 3 H), 7.01–6.97 (m, 2 H). 13C NMR (126 MHz, CDCl3): δ = 150.5 (d, J = 9.9 Hz), 137.1 (d, J = 3.6 Hz), 136.0 (d, J = 7.5 Hz), 133.8 (d, J = 2.8 Hz), 130.6 (d, J = 11.0 Hz), 129.19 (d, J = 2.5 Hz), 129.13 (d, J = 2.9 Hz), 128.5 (d, J = 14.9 Hz), 126.6, 125.73, 125.0 (d, J = 1.0 Hz), 124.8, 123.3 (d, J = 11.2 Hz), 122.1 (d, J = 7.2 Hz), 122.0 (d, J = 11.7 Hz), 120.2 (d, J = 7.0 Hz). 31P NMR (202 MHz, CDCl3): δ = 31.2. Se-Benzyl O,O-Diethyl Phosphoroselenoate (3o) 136 mg (74% yield). The 1H NMR (500 MHz, CDCl3): δ = 7.41–7.32 (m, 2 H), 7.32–7.27 (m, 2 H), 7.26–7.20 (m, 1 H), 4.16–3.98 (m, 6 H), 1.30 (td, J = 7.1, 0.7 Hz, 6 H). 13C NMR (126 MHz, CDCl3): δ = 138.5 (d, J = 4.7 Hz), 129.0, 128.7, 127.5, 63.5 (d, J = 5.5 Hz), 29.5 (d, J = 4.6 Hz), 16.0 (d, J = 7.5 Hz). 31P NMR (202 MHz, CDCl3): δ = 20.2. Se-Benzyl O,O-Diphenyl Phosphoroselenoate (3p) 193 mg (80% yield). 1H NMR (500 MHz, CDCl3): δ = 7.28–7.24 (m, 4 H), 7.16–7.12 (m, 11 H), 4.08 (d, J = 12.6 Hz, 2 H). 13C NMR (126 MHz, CDCl3): δ = 137.2 (d, J = 6.0 Hz), 129.9 (d, J = 1.3 Hz), 129.2, 128.8, 127.7, 125.8 (d, J = 1.7 Hz), 121.0 (d, J = 4.9 Hz), 120.4, 30.9 (d, J = 4.8 Hz). 31P NMR (202 MHz, CDCl3): δ = 13.7. Se-Benzyl Diphenylphosphinoselenoate (3q) 174 mg (78% yield). 1H NMR (500 MHz, CDCl3): δ = 7.94–7.78 (m, 4 H), 7.55–7.49 (m, 2 H), 7.48–7.35 (m, 4 H), 7.20–7.10 (m, 5 H), 4.07 (d, J = 8.3 Hz, 2 H). 13C NMR (126 MHz, CDCl3): δ = 137.7 (d, J = 4.4 Hz), 134.6, 133.8, 132.4 (d, J = 3.1 Hz), 131.4 (d, J = 10.9 Hz), 129.2, 128.8, 128.7 (d, J = 5.2 Hz), 127.3, 28.4 (d, J = 2.5 Hz). 31P NMR (202 MHz, CDCl3): δ = 40.0. 6-(Benzylselanyl)dibenzo[c,e][1,2]oxaphosphinine 6-Oxide (3r) 165 mg (71% yield). 1H NMR (500 MHz, CDCl3): δ = 7.95–7.84 (m, 3 H), 7.70–7.65 (m, 1 H), 7.49 (tdd, J = 7.6, 3.6, 0.9 Hz, 1 H), 7.38–7.33 (m, 1 H), 7.29–7.19 (m, 6 H), 7.11–7.05 (m, 1 H), 4.24–4.09 (m, 2 H). 13C NMR (126 MHz, CDCl3): δ = 149.4 (d, J = 9.8 Hz), 137.7 (d, J = 4.4 Hz), 135.6 (d, J = 7.6 Hz), 133.8 (d, J = 2.7 Hz), 130.8, 130.4 (d, J = 11.9 Hz), 129.2, 128.7 (t, J = 7.5 Hz), 127.8, 127.5, 126.8, 125.2 (d, J = 1.1 Hz), 125.1 (d, J = 0.6 Hz), 123.8 (d, J = 10.9 Hz), 122.3 (d, J = 12.3 Hz), 120.6 (d, J = 6.6 Hz), 29.2 (d, J = 3.7 Hz). 31P NMR (202 MHz, CDCl3): δ = 33.6. O,O-Diethyl S-Phenyl Phosphorothioate (3s) 84 mg (57% yield). 1H NMR (500 MHz, CDCl3): δ = 7.59–7.52 (m, 2 H), 7.37–7.31 (m, 3 H), 4.25–4.12 (m, 4 H), 1.30 (td, J = 7.1, 0.9 Hz, 6 H). 13C NMR (126 MHz, CDCl3): δ = 134.6 (d, J = 5.2 Hz), 129.5 (d, J = 2.2 Hz), 129.1 (d, J = 2.8 Hz), 126.7 (d, J = 7.2 Hz), 64.2 (d, J = 6.2 Hz), 16.1 (d, J = 7.2 Hz). 31P NMR (202 MHz, CDCl3): δ = 22.9. S-Phenyl Diphenylphosphinothioate (3t) 124 mg (66% yield). 1H NMR (500 MHz, CDCl3): δ = 7.88–7.81 (m, 4 H), 7.53–7.48 (m, 2 H), 7.47–7.41 (m, 6 H), 7.26–7.22 (m, 1 H), 7.22–7.17 (m, 2 H). 13C NMR (126 MHz, CDCl3): δ = 135.5 (d, J = 3.9 Hz), 133.1, 132.4 (d, J = 3.0 Hz), 131.7 (d, J = 10.2 Hz), 129.2 (d, J = 1.7 Hz), 129.0 (d, J = 2.2 Hz), 128.6 (d, J = 13.1 Hz), 126.3 (d, J = 5.2 Hz). 31P NMR (202 MHz, CDCl3): δ = 41.3. 6-(Phenylthio)dibenzo[c,e][1,2]oxaphosphinine 6-Oxide (3u) 135 mg (69% yield). 1H NMR (500 MHz, CDCl3): δ = 7.96–7.89 (m, 1 H), 7.86–7.81 (m, 1 H), 7.75 (dd, J = 7.8, 1.6 Hz, 1 H), 7.70–7.65 (m, 1 H), 7.50 (tdd, J = 7.5, 3.6, 1.0 Hz, 1 H), 7.38–7.34 (m, 1 H), 7.28–7.16 (m, 5 H), 7.12–7.06 (m, 2 H). 13C NMR (126 MHz, CDCl3): δ = 150.6 (d, J = 9.6 Hz), 136.4 (d, J = 7.3 Hz), 136.1 (d, J = 4.3 Hz), 133.8 (d, J = 2.6 Hz), 130.9 (d, J = 10.2 Hz), 130.6, 129.4 (d, J = 3.1 Hz), 129.1 (d, J = 2.6 Hz), 128.5 (d, J = 14.9 Hz), 125.4, 124.7, 124.3 (d, J = 4.9 Hz), 123.3 (d, J = 11.5 Hz), 121.9 (d, J = 11.6 Hz), 120.1 (d, J = 7.1 Hz). 31P NMR (202 MHz, CDCl3): δ = 34.2.
  • 15 Zhang X, Wang C, Jiang H, Sun L. Chem. Commun. 2018; 54: 8781
    CrossrefPubMed