A New Approach to the S–H Insertion Reaction of α-Keto Esters and Thiols

Abstract

Sulfur-containing compounds are well known for their frequent occurrence in a large number of natural and synthetic molecules with relevant biological activity. An easy and highly efficient approach to sulfur-containing compounds, by S–H insertion reactions of α-keto esters with thiols, is reported. The substrate scope was remarkably wide, affording the corresponding products in up to 97% yield. Overall, the raw materials were readily available and the reaction conditions were mild in this synthetic method.

Key words

sulfur-containing compounds - S–H insertion reactions - α-keto esters - thiols

Publication History

Received: 06 March 2023

Accepted after revision: 12 April 2023

Article published online:
12 May 2023

• References and Notes

• 1a Sobal G, Menzel EJ, Sinzinger H. Biochem. Pharmacol. 2001; 61: 373
• 1b Halama A, Jirman J, Boušková O, Gibala P, Jarrah K. Org. Process Res. Dev. 2010; 14: 425
• 1c Clayden J, MacLellan P. Beilstein J. Org. Chem. 2011; 7: 582
• 1d Suhas R, Chandrashekar S, Gowda DC. Eur. J. Med. Chem. 2012; 48: 179
• 1e Feng M, Tang B, Liang SH, Jiang X. Curr. Top. Med. Chem. 2016; 16: 1200
• 1f Zhang Z, Dai Z, Jiang X. Asian J. Org. Chem. 2016; 5: 52
• 1g Fukaya M, Nakamura S, Nakagawa R, Kinka M, Nakashima S, Matsuda H. J. Nat. Med. 2019; 73: 397
• 1h Wang N, Saidhareddy P, Jiang X. Nat. Prod. Rep. 2020; 37: 246
• 1i Shen D, Hensley K, Denton TT. Anal. Biochem. 2020; 591: 113543
• 2 Xu B, Zhu SF, Zhang ZC, Yu ZX, Ma Y, Zhou QL. Chem. Sci. 2014; 5: 1442
• 3a Thieme TM, Steri R, Proschak E, Paulke A, Schneider G, Schubert-Zsilavecz M. Bioorg. Med. Chem. Lett. 2010; 20: 2469
• 3b Hieke M, Greiner C, Thieme TM, Schubert-Zsilavecz M, Werz O, Zettl H. Bioorg. Med. Chem. Lett. 2011; 21: 1329
• 4a Zhang YZ, Zhu SF, Cai Y, Mao HX, Zhou QL. Chem. Commun. 2009; 5362
• 4b Gillingham D, Fei N. Chem. Soc. Rev. 2013; 42: 4918
• 4c Shiri L, Ghorbani-Choghamarani A, Kazemi M. Aust. J. Chem. 2016; 69: 585
• 4d Li L, Ding Y. Mini-Rev. Org. Chem. 2017; 14: 407
• 4e Wu R, Huang K, Qiu G, Liu JB. Synthesis 2019; 51: 3567
• 5a Keipour H, Jalba A, Delage-Laurin L, Ollevier T. J. Org. Chem. 2017; 82: 3000
• 5b Keipour H, Jalba A, Tanbouza N, Carreras V, Ollevier T. Org. Biomol. Chem. 2019; 17: 3098
• 5c Tanbouza N, Keipour H, Ollevier T. RSC Adv. 2019; 9: 31241
• 6 Bernardim B, Couch ED, Hardman-Baldwin AM, Burtoloso AC. B, Mattson AE. Synthesis 2016; 48: 677
• 7 Yi X, Feng J, Huang F, Baell JB. Chem. Commun. 2020; 56: 1243
• 8a Sreenilayam G, Moore EJ, Steck V, Fasan R. Adv. Synth. Catal. 2017; 359: 2076
• 8b Chen K, Zhang SQ, Brandenberg OF, Hong X, Arnold FH. J. Am. Chem. Soc. 2018; 140: 16402
• 9 Yan K, He H, Li J, Luo Y, Lai R, Guo L, Wu Y. Chin. Chem. Lett. 2021; 32: 3984
• 10 Huang T, Liu L, Wang QH, Kong DL, Wu MS. Synthesis 2020; 52: 2689
• 11a Ramirez F. Acc. Chem. Res. 1968; 1: 168
• 11b Nifantiev EE, Grachev MK, Burmistrov SY. Chem. Rev. 2000; 100: 3755
• 11c Osman FH, El-Samahy FA. Chem. Rev. 2002; 102: 629
• 12a Fauduet H, Burgada R. Synthesis 1980; 642
• 12b Zhou R, Yang CJ, Liu YY, Li RF, He ZJ. J. Org. Chem. 2014; 79: 10709
• 12c Wilson EE, Rodriguez KX, Ashfeld BL. Tetrahedron 2015; 71: 5765
• 12d Jiang J, Liu H, Lu CD, Xu YJ. J. Org. Chem. 2017; 82: 811
• 12e Tan PW, Wang HR, Wang SR. Org. Lett. 2021; 23: 2590
• 13a Zhou R, Zhang K, Chen YS, Meng Q, Liu YY, Li RF, He ZJ. Chem. Commun. 2015; 51: 14663
• 13b Rodriguez KX, Vail JD, Ashfeld BL. Org. Lett. 2016; 18: 4514
• 13c Zhou R, Zhang K, Han L, Chen YS, Li RF, He ZJ. Chem. Eur. J. 2016; 22: 5883
• 13d Eckert KE, Ashfeld BL. Org. Lett. 2018; 20: 2315
• 13e Liu RF, Liu JL, Cao JL, Li RF, Zhou R, Qiao Y, Gao WC. Org. Lett. 2020; 22: 6922
• 14 Wang SR, Radosevich AT. Org. Lett. 2013; 15: 1926
• 15a Miller EJ, Zhao W, Herr JD, Radosevich AT. Angew. Chem. Int. Ed. 2012; 51: 10605
• 15b Zhao W, Fink DM, Labutta CA, Radosevich AT. Org. Lett. 2013; 15: 3090
• 15c Zhao W, Yan PK, Radosevich AT. J. Am. Chem. Soc. 2015; 137: 616
• 15d Liu Y, Sun F, He Z. Tetrahedron Lett. 2018; 59: 4136
• 16 General procedure: P(NMe₂)₃ (0.15 mmol) was added to a solution of α-keto ester (2, 0.1 mmol) in dry DCM (0.5 mL) at –78 °C, and the resulting mixture was stirred for 5 min at the same temperature. Thiol (1, 0.1 mmol) was then added to the above solution at –78 °C. After being stirred for 5 min at –78 °C, the mixture was left to stir at room temperature for 8 h. After the reaction had finished, the solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography over silica gel (petroleum ether/ethyl acetate = 15:1 or 10:1) to afford the desired product 3, which was analyzed with ¹H NMR and ¹³C NMR spectroscopy (see Supporting Information). Typical data for representative compound 3aa: R_f = 0.30 (petroleum ether/ethyl acetate = 10:1), colorless oil (26.4 mg, 97% yield). ¹H NMR (600 MHz, CDCl₃) δ = 7.45 (d, J = 7.2 Hz, 2 H), 7.39–7.37 (m, 2 H), 7.35–7.29 (m, 3 H), 7.28–7.24 (m, 3 H), 4.90 (s, 1 H), 4.18–4.07 (m, 2 H), 1.16 (t, J = 7.2 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 170.6, 135.7, 133.9, 132.7, 129.1, 128.8, 128.6, 128.4, 128.1, 61.9, 56.4, 14.1. HRMS (ESI): m/z calcd for C₁₆H₁₆O₂SNa [M + Na]⁺: 295.0763; found: 295.0769.