Synthesis, Table of Contents Synthesis 2019; 51(22): 4263-4270DOI: 10.1055/s-0039-1690680 paper © Georg Thieme Verlag Stuttgart · New York Metal-Free Hydroamination of Alkynes: A Mild and Concise Synthesis of Thiazolo[3,2-a]indoles and their Cytotoxic Activity Spencer Short a Department of Biology and Chemistry, Nipissing University, 100 College Drive, North Bay, ON P1B 8L7, Canada Email: mukundj@nipissingu.ca , Steven Rhodes a Department of Biology and Chemistry, Nipissing University, 100 College Drive, North Bay, ON P1B 8L7, Canada Email: mukundj@nipissingu.ca , Vishakha S. Bhave b School of Pharmacy, Philadelphia College of Osteopathic Medicine, Suwanee, GA 30024, USA , Ryoga Hojo a Department of Biology and Chemistry, Nipissing University, 100 College Drive, North Bay, ON P1B 8L7, Canada Email: mukundj@nipissingu.ca , Mukund Jha ∗ a Department of Biology and Chemistry, Nipissing University, 100 College Drive, North Bay, ON P1B 8L7, Canada Email: mukundj@nipissingu.ca › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract A metal-free, mild and efficient method for the synthesis of thiazolo[3,2-a]indoles has been developed starting from indoline-2-thiones. The reaction methodology involves first the formation of thermally labile 2-(prop-2-ynylthio)-1H-indole intermediates, which undergo base-mediated intramolecular hydroamination to produce the title compounds in excellent yields. Key words Key wordsindole-fused heterocycles - thiazolo[3,2-a]indoles - metal-free hydroamination - indoline-2-thiones - intramolecular cyclization Full Text References References For recent reviews, see: 1a Brahmachari G. Asian J. Org. Chem. 2018; 7: 1982 1b Passador K, Thorimbert S, Botuha C. Synthesis 2019; 51: 384 1c Nemoto T, Harada S, Nakajima M. Asian J. Org. Chem. 2018; 7: 1730 2 Ciulla MG, Zimmermann S, Kumar K. Org. Biomol. Chem. 2019; 17: 413 3 Staab A, Loeffler J, Said HM, Diehlmann D, Katzer A, Beyer M, Fleischer M, Schwab F, Baier K, Einsele H, Flentje M, Vordermark D. BMC Cancer 2007; 7: 213 4 Ji Q, Gao J, Wang J, Yang C, Hui X, Yan X, Wu X, Xie Y, Wang M. Bioorg. Med. Chem. Lett. 2005; 15: 2891 5 Kuehm-Caubère C, Caubère P, Jamart-Grégoire B, Pfeiffer B, Guardiola-Lemaître B, Manechez D, Renard P. Eur. J. Med. Chem. 1999; 34: 51 6a Takada S, Makisumi Y. Chem. Pharm. Bull. 1984; 32: 872 6b Takada S, Ishizuka N, Sasatani T, Makisumi Y, Jyoyama H, Hatakeyama H, Asanuma F, Hirose K. Chem. Pharm. Bull. 1984; 32: 877 7a Jin Z. Nat. Prod. Rep. 2003; 20: 584 7b Lewis JR. Nat. Prod. Rep. 1999; 16: 389 8 Pedras MS, Abdoli A. RSC Adv. 2017; 7: 23633 9 Gaster LM, Wyman PA. US Patent 5852014, 1998 10 Rhodes S, Short S, Sharma S, Kaur R, Jha M. Org. Biomol. Chem. 2019; 17: 3914 11 Balasubramanian KK, Nagarajan R. Synthesis 1976; 189 12 Heravi MM, Keivanloo A, Rahimizadeh M, Bakavoli M, Ghassemzadeh M. Tetrahedron Lett. 2004; 45: 5747 13 Xiao D, Han L, Sun Q, Chen Q, Gong N, Lv Y, Suzenet F, Guillaumet G, Cheng T, Li R. RSC Adv. 2012; 2: 5054 14 Omar MA, Frey W, Conrad J, Beifuss U. J. Org. Chem. 2014; 79: 10367 15 Veltri L, Grasso G, Rizzi R, Mancuso R, Gabriele B. Asian J. Org. Chem. 2016; 5: 560 16 Heravi MM, Kivanloo A, Rahimzadeh M, Bakavoli M, Ghassemzadeh M, Neumüller B. Tetrahedron Lett. 2005; 46: 1607 17 Majumdar KC, Nath S. Synthesis 2011; 1413 18 Yaroshenko TI, Nakhmanovich AS, Larina LI, Elokhina VN, Amosova SV. Chem. Heterocycl. Compd. 2008; 44: 1129 19 Majumdar KC, Debnath P, Alam S, Maji PK. Tetrahedron Lett. 2007; 48: 7031 20 Huang L, Arndt M, Gooßen K, Heydt H, Gooßen LJ. Chem. Rev. 2015; 115: 2596 21 Patel M, Saunthwal RK, Verma AK. Acc. Chem. Res. 2017; 50: 240 22a Shelke GM, Jha M, Kumar A. Org. Biomol. Chem. 2016; 14: 3450 22b Jha M, Enaohwo O, Guy S. Tetrahedron Lett. 2011; 52: 684 22c Jha M, Enaohwo O, Marcellus A. Tetrahedron Lett. 2009; 50: 7184 23 Jha M, Shelke GM, Cameron TS, Kumar A. J. Org. Chem. 2015; 80: 5272 24 Jha M, Dhiman S, Cameron TS, Kumar D, Kumar A. Org. Lett. 2017; 19: 2038 25 Jha M, Edmunds M, Lund K, Ryan A. Tetrahedron Lett. 2014; 55: 5691 26 Jha M, Davis C, Fazzari J, Vitali M. Tetrahedron Lett. 2014; 55: 7043 27 Li Y, Mück-Lichtenfeld C, Studer A. Angew. Chem. Int. Ed. 2016; 55: 14435 28 Domingo-Legarda P, Soler-Yanes R, Quirós-López MT, Buñuel E, Cárdenas DJ. Eur. J. Org. Chem. 2018; 4900 Supplementary Material Supplementary Material Supporting Information
