Oxidative Ring-Opening Transformation of 5-Acyl-4-pyrones as an Approach for the Tunable Synthesis of Hydroxylated Pyrones and Furans

Abstract

A selective and tunable approach for oxidation of 4-pyrones has been developed via ring-opening transformations leading to various hydroxylated oxaheterocycles. The first step of the strategy includes the base-catalyzed epoxidation of 5-acyl-4-pyrones in the presence of hydrogen peroxide for the effective synthesis of pyrone epoxides in high yields. The epoxides bearing the CO2Et group are reactive molecules that can undergo both pyrone and oxirane ring-opening via deformylation to produce hydroxylated 2-pyrones or 4-pyrones. The acid-promoted transformation led to 3-hydroxy-4-pyrones (24–76% yields), whereas the K2CO3-catalyzed ring-opening process of 2-carbethoxy-4-pyrone epoxides proceeded as an attack of alcohol at the C-3 position bearing the CO2Et group to give functionalized 6-acyl-5-hydroxy-2-pyrones (27–87% yields). The base-catalyzed reaction of 2-aryl-4-pyrone epoxides was followed by ring contraction and the dearoylation process to produce 3-hydroxyfuran-2-carbaldehydes in 42–80% yields. The transformation of 3-aroylchromone epoxides led to flavonols and 3-hydroxybenzofuran-2-carbaldehyde in the acidic and basic conditions, respectively. The prepared hydroxylated heterocycles demonstrated high reactivity for further transformations and low cytotoxicity and are promising fluorophores or UV filters.

Acid-Promoted Multicomponent Reaction To Synthesize 4-Phosphorylated 4H-Chromenes

“…In order to further examine the utility and applicability of our tandem phospha-aldol/alkylation/cyclization/dehydration reaction, we scaled up the reaction to 5 mmol of 3a , with 1-(4-iodophenyl)­ethanone 1h and 2-hydroxy benzaldehyde 2a under optimized reaction conditions, which afforded product 4ah in a slightly diminished yield of 80% (2.14 g) (Scheme (a)). We also demonstrated the synthetic utility of the products by preparing other chromone derivatives . For example, epoxidation product 5ah was obtained in 55% yield by oxidation of 4ah (Scheme (b)), 3-bromo-chromone 5aa was obtained in 58% yield from 4aa when treated with NBS at 80 °C (Scheme (c)), and the Wittig–Horner reaction product of 6aa was obtained in 24% yield from 4-phosphorylated 4 H -chromenes 4aa (Scheme (d))…”