Synthesis of Sulfoximines through Selective Sulfur Alkylation of Sulfinamides Generated In Situ from β-Sulfoximine Esters

Min Han; Lanxin Luo; Zhuo Tang; Guang-xun Li; Qiwei Wang

doi:10.1055/a-2063-4992

Synlett, Table of Contents

Synlett 2023; 34(15): 1829-1833
DOI: 10.1055/a-2063-4992

letter

Synthesis of Sulfoximines through Selective Sulfur Alkylation of Sulfinamides Generated In Situ from β-Sulfoximine Esters

Min Han

^aChengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, P. R. of China

^bUniversity of Chinese Academy of Sciences, Beijing 10049, P. R. of China

,

Lanxin Luo

^cDepartment of Chemistry, Xihua University, Chengdu, 610039, P. R. of China

,

Zhuo Tang

^dNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan 610041, P. R. of China

,

Guang-xun Li ∗

^dNatural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan 610041, P. R. of China

,

Qiwei Wang∗

^aChengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, P. R. of China

^cDepartment of Chemistry, Xihua University, Chengdu, 610039, P. R. of China

› Author Affiliations

Abstract

All articles of this category

Abstract

Over the past decade, the incidence of sulfoximine functional groups in pharmaceuticals and agrochemicals has increased significantly. This increase has led to a range of useful strategies for installing a S(VI) functionality into complex organic molecules. Conventional synthetic methods for forming α-substituted sulfonimidoyl motifs rely on late-stage modifications at sulfur and involve multistep routes. We report the development of an efficient and general method for the synthesis of various α-arylated sulfoximines through a selective S-alkylation. This strategy uses economical and readily available β-sulfoximine esters as precursors of sulfinamides and has been demonstrated by the preparation of 31 sulfoximines in good yields (up to 87%).

Key words

sulfoximines - S-alkylation - sulfinamides - sulfoximine esters

Full Text

References

References and Notes
1 Campos KR, Coleman PJ, Alvarez JC, Dreher SD, Garbaccio RM, Terrett NK, Tillyer RD, Truppo MD, Parmee ER. Science 2019; 363: eaat0805

2a Lücking U. Angew. Chem. Int. Ed. 2013; 52: 9399
2b Frings M, Bolm C, Blum A, Gnamm C. Eur. J. Med. Chem. 2017; 126: 225
2c Sirvent JA, Lücking U. ChemMedChem 2017; 12: 487

3a Walker DP, Zawistoski MP, McGlynn MA, Li J.-C, Kung DW, Bonnette PC, Baumann A, Buckbinder L, Houser JA, Boer J, Mistry A, Han S, Xing L, Guzman-Perez A. Bioorg. Med. Chem. Lett. 2009; 19: 3253
3b Ouvry G, Bihl F, Bouix-Peter C, Christin O, Defoin-Platel C, Deret S, Feret C, Froude D, Hacini-Rachinel F, Harris CS, Hervouet C, Lafitte G, Luzy A.-P, Musicki B, Orfila D, Parnet V, Pascau C, Pascau J, Pierre R, Raffin C, Rossio P, Spiesse D, Taquet N, Thoreau E, Vatinel R, Vial E, Hennequin LF. Bioorg. Med. Chem. Lett. 2018; 28: 1269
3c Loso MR, Benko Z, Buysse A, Johnson TC, Nugent BM, Rogers RB, Sparks TC, Wang NX, Watson GB, Zhu Y. Bioorg. Med. Chem. 2016; 24: 378
3d Liu Y, Xia Q, Fang L. Bioorg. Med. Chem. 2018; 26: 3992
3e Mäder P, Kattner L. J. Med. Chem. 2020; 63: 14243
3f Lücking U, Kosemund D, Böhnke N, Lienau P, Siemeister G, Denner K, Bohlmann R, Briem H, Terebesi I, Bömer U, Schäfer M, Ince S, Mumberg D, Scholz A, Izumi R, Hwang S, von Nussbaum F. J. Med. Chem. 2021; 64: 11651
3g Kang D, Fang Z, Huang B, Lu X, Zhang H, Xu H, Huo Z, Zhou Z, Yu Z, Meng Q, Wu G, Ding X, Tian Y, Daelemans D, De Clercq E, Pannecouque C, Zhan P, Liu X. J. Med. Chem. 2017; 60: 4424

4 Foote KM, Nissink JW. M, McGuire T, Turner P, Guichard S, Yates JW. T, Lau A, Blades K, Heathcote D, Odedra R, Wilkinson G, Wilson Z, Wood CM, Jewsbury PJ. J. Med. Chem. 2018; 61: 9889
5 Lücking U. Org. Chem. Front. 2019; 6: 1319

6a Bizet V, Hendriks CM. M, Bolm C. Chem. Soc. Rev. 2015; 44: 3378
6b Okamura H, Bolm C. Org. Lett. 2004; 6: 1305
6c Zenzola M, Doran R, Degennaro L, Luisi R, Bull JA. Angew. Chem. Int. Ed. 2016; 55: 7203
6d Andresini M, Tota A, Degennaro L, Bull JA. Chem. Eur. J. 2021; 27: 17293

7 Gao B, Li S, Wu P, Moses JE, Sharpless KB. Angew. Chem. Int. Ed. 2018; 57: 1939

8a Davies TQ, Tilby MJ, Ren J, Parker NA, Skolc D, Hall A, Duarte F, Willis MC. J. Am. Chem. Soc. 2020; 142: 15445
8b Zhang Z.-X, Davies TQ, Willis MC. J. Am. Chem. Soc. 2019; 141: 13022

9a Aota Y, Kano T, Maruoka K. Angew. Chem. Int. Ed. 2019; 58: 17661
9b Aota Y, Kano T, Maruoka K. J. Am. Chem. Soc. 2019; 141: 19263

10 Shultz ZP, Scattolin T, Wojtas L, Lopchuk JM. Nat. Synth. 2022; 1: 170

11a Mendonça Matos P, Lewis W, Argent SP, Moore JC, Stockman RA. Org. Lett. 2020; 22: 2776
11b Mendonça Matos P, Lewis W, Moore JC, Stockman RA. Org. Lett. 2018; 20: 3674
11c Aota Y, Maeda Y, Kano T, Maruoka K. Chem. Eur. J. 2019; 25: 15755
11d Moragas T, Liffey RM, Regentová D, Ward J.-PS, Dutton J, Lewis W, Churcher I, Walton L, Souto JA, Stockman RA. Angew. Chem. Int. Ed. 2016; 55: 10047
11e Yu H, Li Z, Bolm C. Angew. Chem. Int. Ed. 2018; 57: 324
11f Briggs EL, Tota A, Colella M, Degennaro L, Luisi R, Bull JA. Angew. Chem. Int. Ed. 2019; 58: 14303

12 Pilathottathil F, Unnikrishnan S, Kaliyamoorthy A. J. Org. Chem. 2022; 87: 14980
13 Yu X, Zhang Y, Liu Y, Li Y, Wang Q. J. Agric. Food Chem. 2019; 67: 4224
14 Zhang Y, Chen S, Liu Y, Wang Q. Org. Process Res. Dev. 2020; 24: 216
15 Sulfoximines 3; General Procedure The appropriate benzylic bromide 2 (0.12mmol) was added to a solution of TBAB (5 mol%) and β-sulfoximine ester 1 (0.1 mmol) in toluene (1 mL) at 25 °C, and the mixture was stirred at 25 °C for about 8 h until the starting material disappeared (TLC). The solution was then directly purified by column chromatography [silica gel, PE–EtOAc (10:1 to 4:1)]. N-[Benzyl(oxido)phenyl-λ⁴-sulfanylidene]-2,2-dimethylpropanamide (3a) White solid; yield: 0.026 g (0.082 mmol, 82%); mp 105–107 °C; TLC: R_f = 0.4 (PE–EtOAc, 4:1; UV). ¹H NMR (400 MHz, CDCl₃): δ = 7.63 (d, J = 7.8 Hz, 3 H), 7.46 (t, J = 7.8 Hz, 2 H), 7.31 (t, J = 7.5 Hz, 1 H), 7.21 (t, J = 7.5 Hz, 2 H), 6.95 (d, J = 7.5 Hz, 2 H), 4.92 (d, J = 13.6 Hz, 1 H), 4.67 (d, J = 13.6 Hz, 1 H), 1.25 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 188.8, 135.9, 133.8, 131.3, 129.1, 129.1, 128.6, 128.5, 127.8, 61.9, 41.7, 27.8. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₂₁NNaO₂S: 338.1185; found: 338.1187.

Supplementary Material

Supporting Information