Visible-Light-Promoted Click [3+2] Cycloaddition of Aziridine with Alkyne: An Efficient Synthesis of Dihydropyrrolidine

Abstract

A photocatalytic [3+2] cycloaddition of aziridines with activated alkynes is reported under visible-light irradiation in the presence of ruthenium catalyst. This chemical transformation provides polysubstituted pyrrolidines in good yields based on the click chemistry philosophy. The reaction successfully represents a primary trial of cyclocarboamination through photocascade catalysis combining energy transfer and redox neutral reactions.

Key words

aziridine - alkyne - dihydropyrrolidine - visible light - click chemistry - photoredox catalysis

Publikationsverlauf

Eingereicht: 20. Februar 2023

Angenommen nach Revision: 24. Mai 2023

Accepted Manuscript online:
24. Mai 2023

Artikel online veröffentlicht:
26. Juni 2023

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• 18 General Procedure for the Synthesis of 2,3-Dihydropyrroles 3 To a stirred solution of aziridine (1 mmol) and alkyne (2 mmol) in isopropyl alcohol (3 mL) was added PhN₂BF₄ (1.5 equiv) and Ru(bpy)₃(BF₄)₂ photocatalyst (2 mol%) at room temperature under visible-light irradiation (blue LED, 3 W, λ = 427 nm). The reaction typically turned yellow or orange/brownish as the reaction progressed. Upon complete consumption of aziridine (TLC control), the reaction was added onto a short SiO₂ flash column (flushed with Et₃N (5%) doped eluent) or an Al₂O₃ (neutral) flash column and eluted with 6.25% ethyl acetate in petroleum ether. Product-containing fractions were concentrated under reduced pressure to leave the corresponding dihydropyrroles 3. Characterization Data of Representative Compounds 3 3,5-Diphenyl-1-tosyl-2,3-dihydro-1H-pyrrole (3a) ¹H NMR (400 MHz, CDCl₃): δ = 7.70–7.65 (m, 2 H), 7.60–7.50 (m, 2 H), 7.49–7.44 (m, 3 H), 7.26–7.21 (m, 2 H), 7.19–7.14 (m, 3 H), 6.79–6.74 (m, 2 H), 5.32 (d, J = 2.4 Hz, 1 H), 4.40 (dd, J = 11.9, 8.7 Hz, 1 H), 3.83 (dd, J = 11.9, 9.4 Hz, 1 H), 3.61 (ddd, J = 10.0, 8.0, 2.3 Hz, 1 H), 2.45 (s, 3 H).¹³C NMR (100 MHz, CDCl₃): δ = 144.9, 142.9, 141.4, 133.4, 132.6, 129.6, 128.9, 128.5, 128.01, 128.0, 127.6, 127.1, 125.9, 120.0, 59.6, 46.9, 21.9. HRMS (ESI): m/z calcd for [C₂₃H₂₁NO₂S + Na⁺]: 398.1191; found: 398.1196. 3-(4-Bromophenyl)-5-phenyl-1-tosyl-2,3-dihydro-1H-pyrrole (3f) ¹H NMR (400 MHz, CDCl₃): δ = 7.69–7.66 (m, 2 H), 7.42–7.30 (m, 5 H), 7.29–7.21 (m, 2 H), 7.29–7.20 (m, 2 H), 6.76–6.65 (m, 2 H), 5.39 (d, J = 2.8 Hz, 1 H), 4.28 (dd, J = 12.6, 9.9 Hz, 1 H), 3.82 (dd, J = 12.6, 7.3 Hz, 1 H), 3.69 (ddd, J = 9.9, 7.2, 2.7 Hz, 1 H), 2.32 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 146.4, 144.0, 142.6, 133.9, 132.6, 131.9, 129.2, 130.1, 129.0, 128.6, 128.0, 127.3, 120.9, 118.1, 59.9, 45.2, 21.6. HRMS (ESI): m/z calcd for [C₂₃H₂₀NO₂SBr + Na⁺]: 476.0296; found: 476.0290. 3-Methyl-3,5-diphenyl-1-tosyl-2,3-dihydro-1H-pyrrole (3k) ¹H NMR (400 MHz, CDCl₃): δ = 7.63–7.56 (m, 2 H), 7.42–7.35 (m, 3 H), 7.33–7.28 (m, 2 H), 7.16–7.08 (m, 3 H), 7.04 (dd, J = 8.0, 0.5 Hz, 2 H), 6.98–6.92 (m, 2 H), 5.40 (s, 1 H), 4.16 (d, J = 12.3 Hz, 1 H), 4.05 (d, J = 12.2 Hz, 1 H), 2.34 (s, 3 H), 2.24 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 147.6, 143.7, 143.5, 133.2, 132.7, 129.2, 128.8, 128.4, 128.3, 127.8, 127.7, 125.9, 125.5, 123.7, 65.6, 48.2, 29.0, 21.5. HRMS (ESI): m/z calcd for [C₂₄H₂₃NO₂S + Na⁺]: 412.1347; found: 412.1345.