N-Heterocyclic Carbene Catalyzed Reassembly of Dibenzyl Ethers: Facile Access to α-Hydroxy Ketones

Abstract

A novel one-pot cascade process of oxidation-initiated, N-heterocyclic carbene catalyzed, reintegration of dibenzyl ethers has been developed for the first time. This protocol allows straightforward access to α-hydroxy ketones from dibenzyl ethers. It is noteworthy that the present method is the first attempt to synthesize benzoin from dibenzyl ether.

Key words

N-heterocyclic carbenes - dibenzyl ethers - hydroxy ketones - ethers - oxidation - benzoin condensation

Publication History

Received: 24 June 2024

Accepted after revision: 16 July 2024

Accepted Manuscript online:
16 July 2024

Article published online:
05 August 2024

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• 28 α-Hydroxy Ketones 2a–l; General Procedure The oxidant BF₄NO (1.0 mmol) was added to a suspension of the appropriate benzyl ether 1 (0.5 mmol) and H₂O (0.6 mmol) in CH₂Cl₂ (10 mL) at rt (18–25 °C), and the mixture was stirred for 6 h. Cs₂CO₃ (1.0 mmol), TBAB (0.05 mmol), and catalyst A (0.15 mmol) were then added, and the resulting suspension was stirred and refluxed for 18 h until most of the ether 1 was consumed (TLC). The suspension was then filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, EtOAc–PE). Bis(4-fluorobenzyl) Ether (1b) Colorless liquid; yield: 0.9 g (79%). ¹H NMR (400 MHz, CDCl₃): δ = 7.47 (d, J = 8.3 Hz, 4 H), 7.21 (d, J = 8.2 Hz, 4 H), 4.48 (s, 4 H). Bis(biphenyl-4-ylmethyl) Ether (1f) White solid; yield: 1.5 g (84%); mp 86–88 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.56 (d, J = 8.0 Hz, 8 H), 7.39 (dd, J = 16.9, 8.0 Hz, 8 H), 7.29 (t, J = 7.3 Hz, 2 H), 4.57 (s, 4 H).