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Continuous flow as a benign strategy for the synthesis of Thioesters via selective C-N bond cleavage

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Abstract

A metal-free C-N bond cleavage of amide functionality has been reported for the efficient and rapid synthesis of thioester in a simple flow system. The feasibility of this method has been investigated with various aliphatic and aromatic thiols with N-acylamide derivatives to deliver the corresponding thioesters. The fruitful outcome of this process includes good to excellent yields, broad functional group compatibility and can afford the thioesters in just 40 s.

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References

  1. Dander JE, Garg NK (2017) Breaking amides using nickel catalysis. ACS Catal 7(2):1413–1423

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Chaudhari MB, Gnanaprakasam B (2019) Recent advances in the metal-catalyzed activation of amide bonds. Chem Asian J 14(1):76–93

    CAS  PubMed  Google Scholar 

  3. Li G, Szostak M (2019) Transition-metal-free activation of amides by N−C bond cleavage. Chem Rec 2019(n/a)

  4. Meng G, Szostak M (2018) N-acyl-Glutarimides: privileged scaffolds in amide N–C bond cross-coupling. Eur J Org Chem 2018(20–21):2352–2365

    CAS  Google Scholar 

  5. Liu C, Szostak M (2017) Twisted amides: from obscurity to broadly useful transition-metal-catalyzed reactions by N−C amide bond activation. Chem Eur J 23(30):7157–7173

    CAS  PubMed  Google Scholar 

  6. Liu X, Yue H, Jia J, Guo L, Rueping M (2017) Synthesis of Amidines from amides using a nickel-catalyzed Decarbonylative Amination through CO extrusion Intramolecular recombination fragment coupling. Chem Eur J 23(49):11771–11775

    CAS  PubMed  Google Scholar 

  7. Guo L, Rueping M (2018) Transition-metal-catalyzed Decarbonylative coupling reactions: concepts, classifications, and applications. Chem Eur J 24(31):7794–7809

    CAS  PubMed  Google Scholar 

  8. Liu C, Szostak M (2018) Decarbonylative cross-coupling of amides. Org Biomol Chem 16(43):7998–8010

    CAS  PubMed  Google Scholar 

  9. Meng G, Shi S, Szostak M (2016) Cross-coupling of amides by N–C bond activation. Synlett 27(18):2530–2540

    CAS  Google Scholar 

  10. Takise R, Muto K, Yamaguchi J (2017) Cross-coupling of aromatic esters and amides. Chem Soc Rev 46(19):5864–5888

    CAS  PubMed  Google Scholar 

  11. Sureshbabu P, Azeez S, Muniyappan N, Sabiah S, Kandasamy J (2019) Chemoselective synthesis of aryl ketones from amides and Grignard reagents via C(O)–N bond cleavage under catalyst-free conditions. J Org Chem 84(18):11823–11838

    CAS  PubMed  Google Scholar 

  12. Li G, Lei P, Szostak M (2018) Transition-metal-free esterification of amides via selective N–C cleavage under mild conditions. Org Lett 20(18):5622–5625

    CAS  PubMed  Google Scholar 

  13. Liu Y, Liu R, Szostak M (2017) Sc(OTf)3-catalyzed synthesis of anhydrides from twisted amides. Org Biomol Chem 15(8):1780–1785

    CAS  PubMed  Google Scholar 

  14. Mishra A, Chauhan S, Verma P, Singh S, Srivastava V (2019) TBHP-initiated Transamidation of secondary amides via C-N bond activation: a metal-free approach. Asian J Org Chem 8(6):853–857

    CAS  Google Scholar 

  15. Weires NA, Caspi DD, Garg NK (2017) Kinetic modeling of the nickel-catalyzed esterification of amides. ACS Catal 7(7):4381–4385

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Weires NA, Baker EL, Garg NK (2016) Nickel-catalysed Suzuki–Miyaura coupling of amides. Nat Chem 8(1):75

    CAS  PubMed  Google Scholar 

  17. Hie L, Nathel NFF, Shah TK, Baker EL, Hong X, Yang Y-F, Liu P, Houk K, Garg NK (2015) Conversion of amides to esters by the nickel-catalysed activation of amide C–N bonds. Nature 524(7563):79

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bourne-Branchu Y, Gosmini C, Danoun G (2017) Cobalt-catalyzed esterification of amides. Chem Eur J 23(42):10043–10047

    CAS  PubMed  Google Scholar 

  19. Wu H, Guo W, Daniel S, Li Y, Liu C, Zeng Z (2018) Fluoride-catalyzed esterification of amides. Chem Eur J 24(14):3444–3447

    CAS  PubMed  Google Scholar 

  20. Wang Q, Liu L, Dong J, Tian Z, Chen T (2019) Metal-free thioesterification of amides generating acyl thioesters. New J Chem 43(24):9384–9388

    CAS  Google Scholar 

  21. Shinkai H, Maeda K, Yamasaki T, Okamoto H, Uchida I (2000) Bis(2-(Acylamino)phenyl) disulfides, 2-(Acylamino)benzenethiols, and S-(2-(Acylamino)phenyl) Alkanethioates as novel inhibitors of Cholesteryl Ester transfer protein. J Med Chem 43(19):3566–3572

    CAS  PubMed  Google Scholar 

  22. Tulla-Puche J, Marcucci E, Prats-Alfonso E, Bayó-Puxan N, Albericio F (2009) NMe amide as a synthetic surrogate for the Thioester moiety in Thiocoraline. J Med Chem 52(3):834–839

    CAS  PubMed  Google Scholar 

  23. Li Y, Giulionatti M, Houghten RA (2010) Macrolactonization of peptide Thioesters catalyzed by imidazole and its application in the synthesis of Kahalalide B and analogues. Org Lett 12(10):2250–2253

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Mori Y, Seki M (2007) A practical synthesis of multifunctional ketones through the Fukuyama coupling reaction. Adv Synth Catal 349(11–12):2027–2038

    CAS  Google Scholar 

  25. Haraguchi R, S-g T, Tokunaga N, S-i F (2018) Palladium-catalyzed Formylation of Alkenylzinc reagents with S-(4-Nitrophenyl) Thioformate. Eur J Org Chem 2018(15):1761–1764

    CAS  Google Scholar 

  26. Modha SG, Mehta VP, Van der Eycken EV (2013) Transition metal-catalyzed C–C bond formation via C–S bond cleavage: an overview. Chem Soc Rev 42(12):5042–5055

    CAS  PubMed  Google Scholar 

  27. Nofiani R, Philmus B, Nindita Y, Mahmud T (2019) 3-Ketoacyl-ACP synthase (KAS) III homologues and their roles in natural product biosynthesis. MedChemComm 10(9):1517–1530

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Aksakal S, Aksakal R, Becer CR (2018) Thioester functional polymers. Polym Chem 9(36):4507–4516

    CAS  Google Scholar 

  29. Grillo MP (2011) Drug-S-acyl-glutathione thioesters: synthesis, bioanalytical properties, chemical reactivity, biological formation and degradation. Curr Drug Metab 12(3):229–244

    CAS  PubMed  Google Scholar 

  30. Kanda Y, Ashizawa T, Kakita S, Takahashi Y, Kono M, Yoshida M, Saitoh Y, Okabe M (1999) Synthesis and antitumor activity of novel thioester derivatives of leinamycin. J Med Chem 42(8):1330–1332

    CAS  PubMed  Google Scholar 

  31. Srivastava P, Schito M, Fattah RJ, Hara T, Hartman T, Buckheit Jr RW, Turpin JA, Inman JK, Appella E (2004) Optimization of unique, uncharged thioesters as inhibitors of HIV replication. Biorg Med Chem 12(24):6437–6450

    CAS  Google Scholar 

  32. Temperini A, Annesi D, Testaferri L, Tiecco M (2010) A simple acylation of thiols with anhydrides. Tetrahedron Lett 51(41):5368–5371

    CAS  Google Scholar 

  33. Iranpoor N, Firouzabadi H, Etemadi-Davan E, Nematollahi A, Firouzi HR (2015) A novel nickel-catalyzed synthesis of thioesters, esters and amides from aryl iodides in the presence of chromium hexacarbonyl. New J Chem 39(8):6445–6452

    CAS  Google Scholar 

  34. Wang L, Cao J, Chen Q, He M-y (2014) Iron-catalyzed thioesterification of methylarenes with thiols in water. Tetrahedron Lett 55(52):7190–7193

    CAS  Google Scholar 

  35. Feng J, Lu GP, Cai C (2014) Selective approach to thioesters and thioethers via sp3 C–H activation of methylarenes. RSC Adv 4(97):54409–54415

    CAS  Google Scholar 

  36. Yan K, Yang D, Wei W, Zhao J, Shuai Y, Tian L, Wang H (2015) Catalyst-free direct decarboxylative coupling of α-keto acids with thiols: a facile access to thioesters. Org Biomol Chem 13(26):7323–7330

    CAS  PubMed  Google Scholar 

  37. Abenante L, Penteado F, Vieira MM, Perin G, Alves D, Lenardão EJ (2018) Ultrasound-enhanced Ag-catalyzed decarboxylative coupling between α-keto acids and disulfides for the synthesis of thioesters. Ultrason Sonochem 49:41–46

    CAS  PubMed  Google Scholar 

  38. Ali W, Guin S, Rout SK, Gogoi A, Patel BK (2014) Thioesterification of Alkylbenzenes with Thiols via copper- catalyzed cross-Dehydrogenative coupling without a directing group. Adv Synth Catal 356(14–15):3099–3105

    CAS  Google Scholar 

  39. Zhang Y, Ji P, Hu W, Wei Y, Huang H, Wang W (2019) Organocatalytic transformation of aldehydes to Thioesters with visible light. Chem Eur J 25(35):8225–8228

    CAS  PubMed  Google Scholar 

  40. Mukherjee S, Patra T, Glorius F (2018) Cooperative catalysis: a strategy to synthesize Trifluoromethyl-thioesters from aldehydes. ACS Catal 8(7):5842–5846

    CAS  Google Scholar 

  41. Basu B, Paul S, Nanda AK (2010) Silica-promoted facile synthesis of thioesters and thioethers: a highly efficient, reusable and environmentally safe solid support. Green Chem 12(5):767–771

    CAS  Google Scholar 

  42. Banerjee S, Das J, Alvarez RP, Santra S (2010) Silica nanoparticles as a reusable catalyst: a straightforward route for the synthesis of thioethers, thioesters, vinyl thioethers and thio-Michael adducts under neutral reaction conditions. New J Chem 34(2):302–306

    CAS  Google Scholar 

  43. Zheng X, Fu W, Xiong J, Xi J, Ni X, Tang T (2016) Zeolite Beta nanoparticles assembled cu catalysts with superior catalytic performances in the synthesis of thioesters by cross-coupling of aldehydes and disulfides. Catal Today 264:152–157

    CAS  Google Scholar 

  44. Yi C-L, Huang Y-T, Lee C-F (2013) Synthesis of thioesters through copper-catalyzed coupling of aldehydes with thiols in water. Green Chem 15(9):2476–2484

    CAS  Google Scholar 

  45. Huang Y-T, Lu S-Y, Yi C-L, Lee C-F (2014) Iron-catalyzed synthesis of Thioesters from Thiols and aldehydes in water. J Org Chem 79(10):4561–4568

    CAS  PubMed  Google Scholar 

  46. Zeng J-W, Liu Y-C, Hsieh P-A, Huang Y-T, Yi C-L, Badsara SS, Lee C-F (2014) Metal-free cross-coupling reaction of aldehydes with disulfides by using DTBP as an oxidant under solvent-free conditions. Green Chem 16(5):2644–2652

    CAS  Google Scholar 

  47. Jhuang H-S, Liu Y-W, Reddy DM, Tzeng Y-Z, Lin W-Y, Lee C-F (2018) Microwave-assisted synthesis of Thioesters from aldehydes and Thiols in water. J Chin Chem Soc 65(1):24–27

    CAS  Google Scholar 

  48. Hirschbeck V, Gehrtz PH, Fleischer I (2018) Metal-catalyzed synthesis and use of Thioesters: recent developments. Chem Eur J 24(28):7092–7107

    CAS  PubMed  Google Scholar 

  49. Li Y, Zhu F, Wang Z, Wu X-F (2016) Synthesis of Thioethers and Thioesters with alkyl Arylsulfinates as the Sulfenylation agent under metal-free conditions. Chem Asian J 11(24):3503–3507

    CAS  PubMed  Google Scholar 

  50. Liao Y-S, Liang C-F (2018) One-pot synthesis of thioesters with sodium thiosulfate as a sulfur surrogate under transition metal-free conditions. Org Biomol Chem 16(11):1871–1881

    CAS  PubMed  Google Scholar 

  51. Kim H, Min KI, Inoue K, Im DJ, Kim DP, Yoshida J (2016) Submillisecond organic synthesis: outpacing fries rearrangement through microfluidic rapid mixing. Science 352(6286):691–694

    CAS  PubMed  Google Scholar 

  52. Yoshida J (2008) Flash chemistry : fast organic synthesis in microsystems. Wiley, Hoboken, N.J

    Google Scholar 

  53. Hsieh CT, Ötvös SB, Wu YC, Mándity IM, Chang FR, Fülöp F (2015) Highly selective continuous-flow synthesis of potentially bioactive Deuterated Chalcone derivatives. ChemPlusChem 80(5):859–864

    CAS  PubMed  Google Scholar 

  54. Porta R, Benaglia M, Puglisi A (2015) Flow chemistry: recent developments in the synthesis of pharmaceutical products. Org Process Res Dev 20(1):2–25

    Google Scholar 

  55. Noel T, Buchwald SL (2011) Cross-coupling in flow. Chem Soc Rev 40(10):5010–5029

    CAS  PubMed  Google Scholar 

  56. Movsisyan M, Delbeke E, Berton J, Battilocchio C, Ley S, Stevens C (2016) Taming hazardous chemistry by continuous flow technology. Chem Soc Rev 45(18):4892–4928

    CAS  PubMed  Google Scholar 

  57. Plutschack MB, Pieber B, Gilmore K, Seeberger PH (2017) The Hitchhiker's guide to flow chemistry(II). Chem Rev 117(18):11796–11893

    CAS  Google Scholar 

  58. Kobayashi S (2016) Flow “fine” synthesis: high yielding and selective organic synthesis by flow methods. Chem Asian J 11(4):425–436

    CAS  PubMed  Google Scholar 

  59. Asadi M, Bonke S, Polyzos A, Lupton DW (2014) Fukuyama reduction and integrated Thioesterification/Fukuyama reduction of Thioesters and acyl chlorides using continuous flow. ACS Catal 4(6):2070–2074

    CAS  Google Scholar 

  60. Zhou N, Shen L, Dong Z, Shen J, Du L, Luo X (2018) Enzymatic synthesis of Thioesters from Thiols and vinyl esters in a continuous-flow microreactor. Catalysts 8(6):249

    Google Scholar 

  61. Kandasamy M, Ganesan B, Hung MY, Lin WY (2019) Fast and efficient continuous flow method for the synthesis of Ynones and Pyrazoles. Eur J Org Chem 20:3183–3189

    Google Scholar 

  62. Kandasamy M, Huang Y-H, Ganesan B, Senadi GC, Lin W-Y (2019) In situ generation of Alkynylzinc and its subsequent Negishi reaction in a flow reactor. Eur J Org Chem 2019(27):4349–4356

    CAS  Google Scholar 

  63. Shiba SA (1998) Decomposition of 2-Propenoyl Azide derivatives. Synthesis and Larvicidal activity of novel products. Arch Pharm 331(3):91–96

    CAS  Google Scholar 

  64. Hawkins D, Lindley JM, McRobbie IM, Meth-Cohn O (1980) Competitive cyclisations of singlet and triplet nitrenes. Part 9. 2-(2-Nitrenophenyl)-benzothiazoles and -benzimidazoles. J Chem Soc Perkin Trans 1(0):2387–2391

    Google Scholar 

  65. Arisawa M, Yamada T, Yamaguchi M (2010) Rhodium-catalyzed interconversion between acid fluorides and thioesters controlled using heteroatom acceptors. Tetrahedron Lett 51(47):6090–6092

    CAS  Google Scholar 

  66. Singh P, Peddinti RK (2017) Harnessing the catalytic behaviour of 1, 1, 1, 3, 3, 3-hexafluoro-2-propanol (HFIP): an expeditious synthesis of thioesters. Tetrahedron Lett 58(19):1875–1878

    CAS  Google Scholar 

  67. He C, Qian X, Sun P (2014) Syntheses of thiol and selenol esters by oxidative coupling reaction of aldehydes with RYYR (Y = S, se) under metal-free conditions. Org Biomol Chem 12(32):6072–6075

    CAS  PubMed  Google Scholar 

  68. Qi X, Li C-L, Jiang L-B, Zhang W-Q, Wu X-F (2016) Palladium-catalyzed alkoxycarbonylation of aryl halides with phenols employing formic acid as the CO source. Catalysis Science & Technology 6(9):3099–3107

    CAS  Google Scholar 

  69. Feng J, Lv MF, Lu GP, Cai C (2015) Direct oxidative coupling of thiols and benzylic ethers via C(sp3)–H activation and C–O cleavage to lead thioesters. Org Biomol Chem 13(3):677–681

    CAS  PubMed  Google Scholar 

  70. Qiao Z, Jiang X (2016) Ligand-controlled divergent cross-coupling involving Organosilicon compounds for Thioether and Thioester synthesis. Org Lett 18(7):1550–1553

    CAS  PubMed  Google Scholar 

  71. Maphupha M, Juma WP, de Koning CB, Brady D (2018) A modern and practical laccase-catalysed route suitable for the synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles. RSC Adv 8(69):39496–39510

    CAS  Google Scholar 

  72. Nakaya R, Yorimitsu H, Oshima K (2011) Bis (cyclopentadienyldicarbonyliron) as a convenient carbon monoxide source in palladium-catalyzed Carbonylative coupling of aryl iodides with amines, alcohols, and Thiols. Chem Lett 40(9):904–906

    CAS  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge funding from the Ministry of Science and Technology (MOST 106-2113-M-037-009-), Taiwan, Kaohsiung Medical University Research Foundation (KMU-M109004) and the Center for Research Resources and Development of Kaohsiung Medical University for Mass and 400 MHz NMR analyses.

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  1. Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan, Republic of China

    Mohanraj Kandasamy, Antolin Jesila Jesu Amalraj, Gopi Perumal, Balaji Ganesan & Wei-Yu Lin

  2. Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur, Chennai, -603203, India

    Gopal Chandru Senadi

  3. Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, 80708, Taiwan, Republic of China

    Wei-Yu Lin

  4. Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan, Republic of China

    Wei-Yu Lin

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  1. Mohanraj Kandasamy
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  3. Gopi Perumal
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Correspondence to Wei-Yu Lin.

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Kandasamy, M., Amalraj, A.J.J., Perumal, G. et al. Continuous flow as a benign strategy for the synthesis of Thioesters via selective C-N bond cleavage. J Flow Chem 10, 507–515 (2020). https://doi.org/10.1007/s41981-020-00090-w

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