Synthesis and Characterization of New Bulky α‐Hydroxy Ketones by N‐Heterocyclic Carbene‐Catalyzed Intramolecular Benzoin Condensation

Abstract

AbstractIntramolecular benzoin condensation, which is a powerful and useful method for the formation of carbon−carbon bonds from aldehydes, is also an advantageous method for the preparation of a wide variety of α‐hydroxy ketones. The α‐Hydroxy carbonyl groups are an important structure for natural products, industrial, and pharmaceutical materials. In this study, it was aimed to synthesize new bulky α‐hydroxy ketones that can be used both as pharmaceutical materials and can lead to the synthesis of new organocatalysts. An effective method was applied for the synthesis of bulky hydroxy ketones 2 a–l using intramolecular benzoin condensation catalyzed by N‐heterocyclic carbene (I) from 4‐arenoxybenzaldehyde 1 a–f or 4‐thioetherbenzaldehyde 1 g–l derivatives and 12 new bulky α‐hydroxy ketone compounds 2 a–l were synthesized in 70–87 % isolated yield. The synthesized compounds were characterized by spectroscopic and chromatographic methods such as FT‐IR, NMR, LC–MS, and CHN analysis. Additionally, compound 2 h selected as a model substrate was converted into 1,2 diol 3 h, 1,2‐diketone 4 h, and 1,2‐keto acetate 5 h derivatives, and structural analyses were performed. Moreover, chiral hydroxy ketone 2 h was obtained with 100 % ee due to the enzymatic hydrolysis reaction catalyzed by Lipase from Candida rugosa (CRL).