Regioselective Ring Opening of Oxetanes Enabled by Zirconocene and Photoredox Catalysis

Abstract

Oxetanes are frequently utilized in organic synthesis, both as target products and as fairly reactive intermediates. Whereas ring cleavage of oxetanes through polar mechanisms has been extensively investigated, their radical-based counterparts remain underexplored. We used zirconocene and photoredox catalysis to open an oxetane ring in a radical manner. In our protocol, the reaction selectively delivers the more-substituted alcohols via putative less-stable radicals. This method not only affords the corresponding hydrogenated products, but also provides unique benzylidene acetal products.

Key words

zirconocene - photoredox catalysis - oxetanes - reverse regioselectivity - C–O bond homolysis - radicals

Publication History

Received: 01 July 2023

Accepted after revision: 14 August 2023

Article published online:
27 October 2023

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• 16 2-Hydroxybutyl Benzoate (2A); Typical Procedure 1,4-CHD (58.6 μL, 0.60 mmol, 3.0 equiv) and oxetane 1A (0.20 mmol, 1.0 equiv) were added to a solution of Ir(4-MeOppy)₃ (4.5 mg, 6.0 μmol, 3.0 mol%), Cp₂Zr(OTf)₂·THF (5.9 mg, 10 μmol, 5.0 mol%), and TU1 (20.0 mg, 120 μmol, 60 mol%) in THF (2.0 mL), and the resulting mixture was irradiated with a 456 nm LED (Kessil) for 12 h. The mixture was then passed through a short silica gel pad with EtOAc as an eluent, and the filtrate was concentrated in vacuo. The residue was purified by preparative TLC (hexane/EtOAc = 2:1, then CHCl₃/acetone = 9:1) to afford a colorless oil [Run 1; yield: 32.0 mg (84%), Run 2; yield: 24.4 mg (65%)]. ¹H NMR (400 MHz, CDCl₃): δ = 8.08–8.04 (m, 2 H), 7.60–7.55 (m, 1 H), 7.48–7.43 (m, 2 H), 4.41 (dd, J = 11.6, 3.2 Hz, 1 H), 4.25 (dd, J = 11.6, 6.4 Hz, 1 H), 3.96–3.89 (m, 1 H), 2.08 (d, J = 4.8 Hz, 1 H), 1.68–1.56 (m, 2 H), 1.04 (t, J = 7.2 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 166.7, 133.1, 129.9, 129.6, 128.4, 71.4, 68.8, 26.4, 9.8. The spectra were in accordance with those reported in the literature.¹⁷
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