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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
a   Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, P. R. of China
b   University of Chinese Academy of Sciences, Beijing 10049, P. R. of China
,
Lanxin Luo
c   Department of Chemistry, Xihua University, Chengdu, 610039, P. R. of China
,
Zhuo Tang
d   Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan 610041, P. R. of China
,
Guang-xun Li  ∗
d   Natural Products Research Center, Chengdu Institution of Biology, Chinese Academy of Science, Chengdu, Sichuan 610041, P. R. of China
,
Qiwei Wang∗
a   Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, P. R. of China
c   Department of Chemistry, Xihua University, Chengdu, 610039, P. R. of China
› Author AffiliationsThe West Light Foundation of the Chinese Academy of Sciences (25E0C30), and the Sichuan Province Science and Technology Support Program (2021ZYD0061).
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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

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2063-4992.
  • Supporting Information


Publication History

Received: 17 February 2023

Accepted after revision: 28 March 2023

Accepted Manuscript online:
28 March 2023

Article published online:
11 May 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
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  • 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: Rf = 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.