Transition-Metal-Free N-(o-Halo)arylation of Sulfoximines/Sulfonimidamides

Abstract

A transition-metal-free novel route to access N-(o-halo)arylsulfoximines/sulfonimidamides is achieved by the reaction of sulfoximine/sulfonimidamide, aryne precursor, and CCl₄/CBr₄ in the presence of KF/18-crown-6. The in situ generated benzyne intermediate (from silyl aryl triflate) reacts with the nucleophile (sulfoximine/sulfonimidamide) and halide source (CCl₄/CBr₄) to yield the product in moderate to good yield. The protocol exhibits broad substrate scope. The regioisomers formed from the unsymmetric aryne precursor were separated effectively via column chromatography.

Key words

aryne precursor - carbon tetrahalide - sulfoximine - sulfonimidamide - transition-metal-free route

Publication History

Received: 27 May 2022

Accepted after revision: 08 August 2022

Accepted Manuscript online:
08 August 2022

Article published online:
09 September 2022

• References and Notes

• 1a Reggelin M, Zur C. Synthesis 2000; 1
• 1b Ghosh P, Ganguly P, Das S. Asian J. Org. Chem. 2020; 9: 2035
• 1c Andresini M, Tota A, Degennaro L, Bull JA. Chem. Eur. J. 2021; 27: 17293
• 2a Lucking U. Angew. Chem. Int. Ed. 2013; 52: 9399
• 2b Natarajan K, Jesin CP. I, Mercy AA. H, Nandi GC. Org. Biomol. Chem. 2021; 19: 7061
• 2c Priya VR. P, Natarajan K, Nandi GC. Tetrahedron 2022; 111: 132711
• 3a Harmata M, Hong X. J. Am. Chem. Soc. 2003; 125: 5754
• 3b Koep S, Gais HJ, Raabe G. J. Am. Chem. Soc. 2003; 125: 13243
• 3c Craig D, Grellepois F, White AJ. P. J. Org. Chem. 2005; 70: 6827
• 4a Bolm C, Martin M, Simic O, Verrucci M. Org. Lett. 2003; 5: 427
• 4b Moessner C, Bolm C. Angew. Chem. Int. Ed. 2005; 44: 7564
• 4c Sedelmeier J, Hammerer T, Bolm C. Org. Lett. 2008; 10: 917
• 5a Bolm C, Moll G, Kahmann JD. Chem. Eur. J. 2001; 7: 1118
• 5b Hackenberger CP. R, Raabe G, Bolm C. Chem. Eur. J. 2004; 10: 2942
• 6a Oshiro Y, Sato S, Kurahashi N, Tanaka T, Kikuchi T, Tottori K, Uwahodo Y, Nishi T. J. Med. Chem. 1998; 41: 658
• 6b Havale SH, Pal M. Bioorg. Med. Chem. 2009; 17: 1783
• 6c Kiss B, Horvath A, Nemethy Z, Schmidt E, Laszlovszky I, Bugovics G, Fazekas K, Hornok K, Orosz S, Gyertyan I, Csongor EA, Domany G, Tihanyi K, Adham N, Szombathelyi Z. J. Pharmacol. Exp. Ther. 2010; 333: 328
• 6d Chen X, Sassano MF, Zheng L, Setola V, Chen M, Bai X, Frye SV, Wetsel WC, Roth BL, Jin J. J. Med. Chem. 2012; 55: 7141
• 7 Cho EJ, Senecal TD, Kinzel T, Zhang Y, Watson DA, Buchwald SL. Science 2010; 328: 1679
• 8a Bolm C, Hildebrand JP. J. Org. Chem. 2000; 65: 169
• 8b Sedelmeier J, Bolm C. J. Org. Chem. 2005; 70: 6904
• 8c Moessner C, Bolm C. Org. Lett. 2005; 7: 2667
• 9a Hendrick CE, McDonald SL, Wang Q. Org. Lett. 2013; 15: 3444
• 9b Shi J, Li L, Li Y. Chem. Rev. 2021; 121: 3892
• 10 Aithagani SK, Dara S, Munagala G, Aruri H, Yadav M, Sharma S, Vishwakarma RA, Singh PP. Org. Lett. 2015; 17: 5547
• 11a Appel R. Angew. Chem., Int. Ed. Engl. 1975; 14: 801
• 11b Castro BR. Org. React. 1983; 29: 1
• 12a Li SJ, Wang Y, Xu JK, Xie D, Tian SK, Yu ZX. Org. Lett. 2018; 20: 4545
• 12b Wang HY, Tian SK. Org. Lett. 2019; 21: 5675
• 13 Xie Y, Zhou B, Zhou S, Zhou S, Wei W, Liu J, Zhan Y, Cheng D, Chen M, Li Y, Wang B, Xue X, Li Z. ChemistrySelect 2017; 2: 1620
• 14a Chinthakindi PK, Naicker T, Thota N, Govender T, Kruger HG, Arvidsson PI. Angew. Chem. Int. Ed. 2017; 56: 4100
• 14b Izzo F, Schafer M, Stockman R, Lucking U. Chem. Eur. J. 2017; 23: 15189
• 14c Nandi GC. Eur. J. Org. Chem. 2017; 6633
• 14d Nandi GC, Arvidsson PI. Adv. Synth. Catal. 2018; 360: 2976
• 14e Jesin CP. I, Nandi GC. Chem. Eur. J. 2019; 25: 743
• 14f Jesin CP. I, Ravindra S, Nandi GC. Tetrahedron 2019; 75: 130622
• 14g Ravindra S, Nayak A, Jesin CP. I, Nandi GC. Adv. Synth. Catal. 2022; 364: 1144
• 14h Nandi GC, Raju C. Org. Biomol. Chem. 2017; 15: 2234
• 15 General Procedure for the Synthesis of 4a–n, 5a–d, 7a–f A clean 20 mL Schlenk tube was charged with the corresponding sulfoximine 1 (30 mg, 0.177 mmol, 1.0 equiv.), KF (41 mg, 0.708 mmol, 4.0 equiv.), and 18-crown-6 (187 mg, 0.708 mmol, 4.0 equiv.). Then, anhydrous THF (1 mL), CCl₄ (69 μL, 0.709 mmol, 4.0 equiv.), and corresponding benzyne precursor (87 μL, 0.355 mmol, 2.0 equiv.) were added sequentially. The reaction mixture was stirred at 65 °C for 12 h. After completion of the reaction (checked by TLC), the solvent was removed in vacuo, and the product 4 was purified through column chromatography (100–200 mesh SiO₂) using 2 - 10% of ethyl acetate in hexane as eluent. CBr₄ was used to obtain compound 5. Compound 7 was prepared following the same method using sulfonimidamide 6. Characterization Data for 4a It was obtained as a pale yellow sticky liquid; yield 66% (33 mg obtained from 0.177 mmol of corresponding sulfoximine). ¹H NMR (400 MHz, CDCl₃): δ = 7.91 (d, J = 8.4 Hz, 2 H), 7.34–7.30 (m, 3 H), 7.18 (dd, J = 8.0, 1.6 Hz, 1 H), 6.97 (td, J = 7.6, 1.6 Hz, 1 H), 6.82 (td, J = 8.0, 1.6 Hz, 1 H), 3.25 (s, 3 H), 2.41 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 144.5, 142.4, 136.1, 130.3, 129.9, 128.7, 128.6, 127.2, 124.0, 122.7, 45.9, 21.7. HRMS (ESI): m/z calcd for C₁₄H₁₄ClNOS [M + H]⁺: 280.0557; found: 280.0563.