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Synlett
DOI: 10.1055/a-2779-2027
Letter
Published as part of the Special Topic Alkynes in Organic Synthesis

Stable Vicinal Bisketene Equivalents for Aryne Diels–Alder Reactions

Authors

  • Jessica E. Budwitz

    1   Department of Chemistry, University of Georgia, Athens, United States (Ringgold ID: RIN1355)

  • Christopher G. Newton 

    1   Department of Chemistry, University of Georgia, Athens, United States (Ringgold ID: RIN1355)

Financial support from the National Institutes of Health (R35GM155161 to C.G.N.) and the University of Georgia is gratefully acknowledged.
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Graphical Abstract

Abstract

2,5-Bis(tert-butyldimethylsilyloxy)thiophenes are introduced as bench-stable Diels–Alder dienes for reaction with arynes as dienophiles. Ring opening of the cycloadducts can be achieved via TBAF-promoted desilylation, providing convergent, redox-neutral access to a library of substituted naphthoquinones. Strategically, this two-step sequence represents the application of stable vicinal bisketene equivalents as Diels–Alder dienes. Extension to anthraquinones is also demonstrated, in this case via mild autoxidation of a readily accessible cyclohexenyl-fused derivative.

Keywords

Diels–Alder - Cycloaddition - Annulation - Thiophene - Aryne - Benzyne - Anthraquinone

Supplementary Material



Publication History

Received: 17 November 2025

Accepted after revision: 10 December 2025

Article published online:
15 January 2026

© 2026. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

    • 2a Kotsuki H, Kitagawa S, Nishizawa H, Tokoroyama T. J Org Chem 1978; 43: 1471
      Search in Google Scholar
    • 2b McCluskey A, Keane MA, Walkom CC. et al. Bioorg Med Chem Lett 2002; 12: 391
      Search in Google Scholar
    • 2c Gilchrist TL, Margetic D, Butler DN, Warrener RN. ARKIVOC 2002; 2002: 234
      Search in Google Scholar
    • 2d Kumamoto K, Fukada I, Kotsuki H. Angew Chem Int Ed 2004; 43: 2015
      Search in Google Scholar
    • 3a Calvo-Martín G, Plano D, Sanmartín C. Molecules 2022; 27: 982
      Search in Google Scholar
    • 3b Cho Y, Kim Y, Seo J, Bielawski CW. ACS Macro Lett 2024; 13: 1509
      Search in Google Scholar
    • 3c Youssif S, Mohamed EK, Sayed Ahmed AF, Ghoneim AA. Bull Korean Chem Soc 2021; 2005: 26
      Search in Google Scholar
  • 4 Isobenzothiophenes are beyond the scope of this review.
    • 5a Callander DD, Coe PL, Tatlow JC. Chem Commun 1966; 143
    • 5b Callander DD, Coe PL, Tatlow JC, Uff AJ. Tetrahedron 1969; 25: 25
      Search in Google Scholar
    • 5c Coe PL, Pearl GM, Tatlow JC. J Chem Soc C 1971; 604
    • 6a Fields EK, Meyerson S. Chem Commun 1966; 708
    • 6b Fields EK, Meyerson S. J Org Chem 1969; 34: 2475
      Search in Google Scholar
    • 6c Reinecke MG, Newsom JG, Chen L-J. J Am Chem Soc 1981; 103: 2760
      Search in Google Scholar
    • 6d Del Mazza D, Reinecke MG. J Org Chem 1988; 53: 5799
      Search in Google Scholar
    • 6e Reinecke MG, Del Mazza D. J Org Chem 1989; 54: 2142
      Search in Google Scholar
  • 7 Zhang M-X, Shan W, Chen Z, Yin J, Yu G-A, Liu SH. Tetrahedron Lett 2015; 56: 6833
    Search in Google Scholar
  • 8 Dissanayake I, Hart JD, Becroft EC, Sumby CJ, Newton CG. J Am Chem Soc 2020; 142: 13328
    Search in Google Scholar

      • For a review of ketene equivalents as dienophiles in the Diels–Alder reaction, see:
    • 9a Mackay EG, Newton CG. Aust J Chem 2016; 69: 1365
      Search in Google Scholar

      • For a recent perspective on ring-forming approaches to para-quinones, see:
    • 9b Budwitz JE, Newton CG. Synlett 2022; 33: 1473
      Search in Google Scholar

      • For application of 2,5-bis(tert-butyldimethylsilyloxy)furans in aza-Diels–Alder reactions, see:
    • 9c DeAngelis CJ, Goyal G, Liss MJ. et al. J Am Chem Soc 2025; 147: 6087
      Search in Google Scholar

      • For a review of hetero-Diels–Alder reactions of (isobenzo)furans, see:
    • 9d DeAngelis CJ, Newton CG. Org Biomol Chem 2025; 23: 9781
      Search in Google Scholar
  • 10 Budwitz JE, Newton CG. Org Synth 2023; 100: 159
    Search in Google Scholar

      • For a comprehensive list of known 2,5-(silyloxy)thiophenes, see:
    • 11a Lozzi L, Ricci A, Taddei M. J Org Chem 1984; 49: 3408
      Search in Google Scholar
    • 11b Rzehak W, Simchen G. Chimia 1987; 41: 152
      Search in Google Scholar
    • 11c Frick U, Simchen G. Liebigs Ann 1987; 839
    • 11d Capon B, Wu ZP. J Org Chem 1989; 54: 1211
      Search in Google Scholar
    • 11e Rzehak W, Simchen G. Liebigs Ann 1992; 615
    • 11f Kates MJ, Schauble JH. J Org Chem 1995; 60: 6676
      Search in Google Scholar
  • 12 We previously reported the stability of furan 2 toward buffered silica as 77% (reference 10). This experiment has since been rerun in triplicate and we revise this value to 90%.
  • 13 From a qualitative perspective, this general stability profile appears to hold true for all thiophenes reported within this study, with the exception of 25, which slowly discolors over a period of days-to-weeks upon storage neat in the freezer (−20 °C) under an air atmosphere. Over this timeframe, NMR analysis shows ca. 10% decomposition.
  • 14 Matsumoto T, Hosoya T, Katsuki M, Suzuki K. Tetrahedron Lett 1991; 32: 6735
    Search in Google Scholar
    • 15a Yoshida S, Uchida K, Igawa K, Tomooka K, Hosoya T. Chem Commun 2014; 50: 15059
      Search in Google Scholar
    • 15b Yoshida S, Nonaka T, Morita T, Hosoya T. Org Biomol Chem 2014; 12: 7489
      Search in Google Scholar
    • 16a Cava MP, Pollack NM, Mamer OA, Mitchell MJ. J Org Chem 1971; 36: 3932
      Search in Google Scholar
    • 16b Mayer R, Kleinert H, Richter S, Gewald K. J Prakt Chem 1963; 20: 244
      Search in Google Scholar
  • 17 Filatov MA, Lebedev AY, Mukhin SN, Vinogradov SA, Cheprakov AV. J Am Chem Soc 2010; 132: 9552
    Search in Google Scholar