Temperature-Controlled Synthesis of Thiophenol-VBXs from EBXs and Thiophenols

Abstract

Vinylbenziodoxolones (VBXs) are important electrophilic alkene synthons. However, the synthesis of cis-thiophenol-VBX reagents from ethynylbenziodoxolones (EBXs) and thiophenols remains challenging. Herein, we explore an efficient method for the synthesis of cis-thiophenol-VBXs in excellent yield with excellent regio- and stereoselectivities from EBXs and thiophenols under temperature-controlled conditions.

Key words

vinylbenziodoxolones - ethynylbenziodoxolones - iodine(III) - thiophenols - temperature control

Publication History

Received: 12 June 2024

Accepted after revision: 31 July 2024

Accepted Manuscript online:
31 July 2024

Article published online:
30 August 2024

• References and Notes


Selected reviews, see:
• 1a Wang D, Li Q, Li M, Du Z, Fu Y. Curr. Org. Chem. 2021; 25: 1298
• 1b Wang Y, An G, Wang L, Han J. Curr. Org. Chem. 2020; 24: 2070

Selected reviews, see:
• 2a Irina AM, Dmitrii MN, Akira Y, Mekhman SY, Viktor VZ. Molecules 2023; 28: 2136
• 2b Du EL, Waser J. Chem. Commun. 2023; 59: 1589
• 3 Liu YW, Dietl MC, Han CY, Rudolph M, Rominger F, Krämer P, Hashmi AS. K. Org. Lett. 2022; 24: 7101
• 4a Frei R, Waser J. J. Am. Chem. Soc. 2013; 135: 9620
• 4b Frei R, Wodrich MD, Hari DP, Borin PA, Chauvier C, Waser J. J. Am. Chem. Soc. 2014; 136: 16563
• 5 Li M, Wang JH, Li W, Wen LR. Org. Lett. 2018; 20: 7694
• 6a Stridfeldt E, Seemann A, Bouma MJ, Dey C, Ertan A, Olofsson B. Chem. Eur. J. 2016; 22: 16066
• 6b Caramenti P, Declas N, Tessier R, Wodrich MD, Waser J. Chem. Sci. 2019; 10: 3223
• 6c Adusumalli SR, Bernardes GJ. L. Chem 2019; 5: 1932
• 6d Vaillant FL, Garreau M, Nicolai S, Grynóva G, Corminboeuf C, Waser J. Chem. Sci. 2018; 9: 5883
• 6e Castoldi L, Tommaso EM. D, Reitti M, Gräfen B, Olofsson B. Angew. Chem. Int. Ed. 2020; 59: 15512
• 6f Castoldi L, Rajkiewicz AA, Olofsson B. Chem. Commun. 2020; 56: 14389
• 7a Liu B, Lim C, Miyake GM. J. Am. Chem. Soc. 2018; 140: 12829
• 7b Wang LF, Shi CR, Qi W, Xu J, Xiong WF, Kang BX, Jiang HF. Chem. Sci. 2021; 12: 11821
• 7c Ura T, Shimbo D, Yudasaka M, Tada N, Itoh A. Chem. Asian J. 2020; 15: 4000
• 7d Woo SY, Kim JH, Moon MK, Han SH, Yeon SK, Choi JW, Jang BK, Song HJ, Kang YG, Kim JW, Lee J, Kim DJ, Hwang O, Park KD. J. Med. Chem. 2014; 57: 1473
• 7e Song ZL, Hou Y, Bai FF, Fang JG. Bioorg. Chem. 2021; 107: 104520
• 8a Wu J, Deng X, Hirao H, Yoshikai N. J. Am. Chem. Soc. 2016; 138: 9105
• 8b Wu J, Xu K, Hirao H, Yoshikai N. Chem. Eur. J. 2017; 23: 1521
• 9a Kitamura T, Fukuoka T, Fujiwara Y. Synthesis 1996; 7: 659
• 9b Shimbo D, Maruyama T, Tada N, Itoh A. Org. Biomol. Chem. 2021; 19: 2442
• 9c Kikuchi J, Maesaki K, Sasaki S, Wang W, Ito S, Yoshikai N. Org. Lett. 2022; 24: 6914
• 10 Wu J, Deng X, Yoshikai N. Chem. Eur. J. 2019; 25: 7839
• 11a Tessier R, Ceballos J, Guidotti N, Simonet-Davin R, Fierz B, Waser J. Chem 2019; 5: 2243
• 11b Liu B, AlegreRequena JV, Paton RS, Miyake GM. Chem. Eur. J. 2020; 26: 2386
• 12a Zhu Y.-S, Xue Y, Liu W, Zhu X, Hao X.-Q, Song M.-P. J. Org. Chem. 2020; 85: 9106
• 12b Kao TT, Peng BK, Liang MC, Lee CJ, Chen IC, Shia KS, Wen YK. J. Org. Chem. 2018; 83: 14688
• 12c Houck HA, Bruycker KD, Kowollik CB, Winne JM, Prez FE. D. Macromolecules 2018; 51 (08) 3156
• 12d Chang MY, Chen HY, Tsai YL. J. Org. Chem. 2019; 84: 326
• 12e Li L, Che YK, Gross DE, Huang HL, Moore JS, Zang L. ACS Macro Lett. 2012; 1: 1335
• 12f Koizumi H, Shiraishi Y, Hirai T. J. Phys. Chem. B 2008; 112: 13238
• 13a He SD, Guo XQ, Li J, Zhang YC, Chen LM, Kang TR. Eur. J. Org. Chem. 2022; e202200516
• 13b Sun X, Guo XQ, Chen LM, Kang TR. Chem. Eur. J. 2021; 27: 4312
• 13c Li J, Zhou C, Liang H, Guo XQ, Chen LM, Kang TR. Eur. J. Org. Chem. 2022; 30: 177
• 13d Xia AJ, Kang TR, He L, Chen LM, Li WY, Yang JL, Liu QZ. Angew. Chem. Int. Ed. 2016; 55: 1441
• 13e Nie X, Wang Y, Yang L, Yang Z, Kang T. Tetrahedron Lett. 2017; 58: 3003
• 13f Zeng L, Guo XQ, Yang ZJ, Gan Y, Chen LM, Kang TR. Tetrahedron Lett. 2019; 60: 150943
• 13g Chen LM, Zhao J, Xia A.-J, Guo XQ, Gan Y, Zhou C, Yang ZJ, Yang J, Kang TR. Org. Biomol. Chem. 2019; 17: 8561
• 13h Chen LM, Zhou C, Li J, Li J, Guo XQ, Kang TR. Org. Biomol. Chem. 2022; 20: 7011
• 13i Chen Y, Guo X, Zhou C, Chen L, Kang TR. Synlett 2019; 30: 851
• 13j Chen L, Liu Z, Nie X, Guo XQ, Kang TR. Synlett 2018; 29: 2390
• 13k Du X, Jiang H, Guo X, Chen L, Kang T. React. Funct. Polym. 2021; 169: 105061
• 13l Liu QP, Chen LM, Zhou C, Guo XQ, Kang TR. Asian J. Org. Chem. 2023; e20220061
• 14 Wodrich MD, Caramenti P, Waser J. Org. Lett. 2016; 18: 60
• 15 Typical Procedure and Characterization Data for 3a: Compound 1a (0.2 mmol, 1.0 equiv), ethanol (2 mL), and Et₃N (0.3 mmol, 1.5 equiv) were added to a flask. The mixture was cooled at –50 °C in a low-temperature reactor. 4-Methylthiophenol 2a (0.22 mmol, 1.1 equiv) was added and the reaction mixture was stirred at –50 °C until 1a was consumed (monitored by TLC). The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography on silica gel (CH₂Cl₂/MeOH) to give pure product 3a (97%, 91.6 mg) as a white solid; mp 162.7–163.5 °C. R_f = 0.30 (CH₂Cl₂/MeOH, 20:1). ¹H NMR (600 MHz, DMSO-d ₆): δ = 8.14 (d, J = 7.3 Hz, 1 H), 7.74 (t, J = 7.5 Hz, 1 H), 7.69 (d, J = 8.3 Hz, 1 H), 7.65 (t, J = 7.3 Hz, 1 H), 7.63–7.59 (m, 3 H), 7.31 (d, J = 6.3 Hz, 3 H), 7.09 (d, J = 7.8 Hz, 2 H), 6.95 (dd, J = 8.3, 2.8 Hz, 2 H), 2.10 (d, J = 3.5 Hz, 3 H). ¹³C NMR (150 MHz, DMSO-d ₆): δ = 166.19, 157.44, 138.26, 136.94, 135.11, 134.17, 132.31, 132.10, 130.96, 130.56, 130.39, 129.35, 129.15, 128.78, 128.64, 127.89, 115.73, 109.95, 21.04. HRMS: m/z [M + Na]⁺ calcd for C₂₂H₁₇IO₂S: 494.9886; found: 494.9890.