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Synlett 2025; 36(04): 347-352
DOI: 10.1055/a-2351-4900
DOI: 10.1055/a-2351-4900
letter
Attempts on Fluorinative Transformation of Selected Functionalized Cycloalkene Scaffolds through Aziridination/Aziridine-Opening Protocol
The authors gratefully acknowledge financial support from the Nemzeti Kutatási Fejlesztési és Innovációs H (National Research, Development and Innovation Office of Hungary, NKFIH/OTKA FK 145394 and K 142266). Project no. RRF-2.3.1-21-2022-00015 has been implemented with the support provided by the European Union. This work was supported by the János Bolyai Research Scholarship to M.N. of the Magyar Tudományos Akadémia (Hungarian Academy of Sciences).
Abstract
Studies on the transformations of some functionalized cycloalkene derivatives through their ring olefin-bond aziridination/aziridine opening with fluoride are presented. The selected model compounds submitted to fluorinative functionalization were an amino ester and diesters with a cyclohexene skeleton as well as a cyclopentene-fused β-lactam. Functionalization proceeded across a substrate-directed diastereoselective olefin-bond aziridination, followed by fluoride-mediated aziridine opening or intramolecular lactonization giving some fluorinated amino ester or amino lactone derivatives.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2351-4900.
- Supporting Information
Publication History
Received: 22 May 2024
Accepted after revision: 24 June 2024
Accepted Manuscript online:
24 June 2024
Article published online:
08 July 2024
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- 13a General Procedure for Aziridination Reactions The appropriate starting material 1 mmol was dissolved in 10 mL MeCN and then cooled down to 0 °C. After that, 1.2 equiv (1.2 mmol, 338 mg) chloramine-T·3H2O and 15 mol% PTAB (0.15 mmol, 56 mg) were added. The mixture was stirred to the appropriate time and then was cooled down. When the reaction was completed, MeCN was evaporated from the mixture and the residue was dissolved in 30 mL EtOAc. The mixture was then washed with 3 ( 10 mL water, and the organic and water phases were separated. The organic phase was dried with anhydrous Na2SO4, filtered, and evaporated under vacuum. Purification of the crude product by column chromatography on silica gel afforded the products as oils or solids.
- 13b Benzyl (1S*,3R*,4S*,6R*)-4-[(tert-Butoxycarbonyl)amino]-7-tosyl-7-azabicyclo[4.1.0]heptane-3-carboxylate (11) Prepared according to aziridination general procedure from benzyl (1R*,6S*)-6-[(tert-butoxycarbonyl)amino]cyclohex-3-ene-1-carboxylate (331 mg, 1.00 mmol) for 5 h. Purification of the crude product by column chromatography on silica gel afforded the product as white-yellowish solid 235 mg; yield 50%. R f = 0.20 (H/E n-hexane/EtOAc, 3:1); mp 50–52 °C. 1H NMR (500 MHz, CDCl3): δ = 7.76 (d, J = 8.3 Hz, 2 H), 7.39–7.28 (m, 7 H), 5.48 (d, J = 10.1 Hz, 1 H), 5.09 (d, J = 12.2 Hz, 1 H), 4.94 (d, J = 12.3 Hz, 1 H), 3.98 (d, J = 8.0 Hz, 1 H), 3.07 (td, J = 4.9, 2.4 Hz, 1 H), 2.98 (ddd, J = 6.8, 5.2, 1.1 Hz, 1 H), 2.58–2.54 (m, 1 H), 2.54–2.50 (m, 1 H), 2.42 (s, 3 H), 2.16–2.06 (m, 2 H), 2.01 (dt, J = 15.1, 7.4 Hz, 1 H), 1.40 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 172.4, 155.0, 144.6, 135.3, 129.8, 128.5, 128.3, 128.2, 127.4, 126.3, 79.4, 66.8, 45.2, 40.3, 38.8, 38.3, 28.3, 27.1, 23.9, 21.6. HRMS: m/z calcd for C26H32N2O6SNa+ [M + Na]+: 523.1879; found: 523.1878.
- 13c General Procedure for Fluorination Reactions The appropriate starting material 1 mmol was dissolved in 15 mL anhydrous 1,4-dioxane, and the temperature was set to the boiling point of the solvent. Then 4 equiv fluorinating reagent (either Xtal-Fluor-E 4.00 mmol, 916 mg or Xtal-Fluor-M 4.00 mmol, 972 mg) was added and the reaction mixture was stirred to the appropriate time. When the reaction was completed, the flask was cooled down to room temperature and 15 mL EtOAc were added to the mixture. It was poured to a separation funnel and washed with 3 ( 15 mL saturated NaHCO3 solution. The organic phase was dried with anhydrous Na2SO4, filtered, and evaporated under vacuum. Purification of the crude product by column chromatography on silica gel afforded the products as oils or solids.
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