An Efficient Directed Claisen Reaction Allows for Rapid Construction of 5,6-Disubstituted 1,3-Dioxin-4-ones

Abstract

An efficient directed Claisen reaction between tert-butyl propionate and phenyl propionate is described. This enables a practical synthesis of 6-ethyl-2,2,5-trimethyl-4H-1,3-dioxin-4-one and thereby (Z)-[(4-ethylidene-2,2,5-trimethyl-4H-1,3-dioxin-6-yl)oxy]trimethylsilane, a key building block in our synthesis of macrolide antibiotics. The three-step route elaborated for the preparation of the latter substance requires no chromatography and is amenable to large-scale synthesis.

Key words

directed Claisen reaction - β-keto ester synthesis - phenyl ester substrate - synthesis of substituted dioxinones - macrolide antibiotics

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