A New Multicomponent Domino Transformation of 1,3-Dicarbonyl Compounds: One-Pot Regio-, Chemo- and Stereoselective Access to Valuable α,γ-Difunctionalized α-Ketoesters and Amides

Abstract

A new multi-component transformation between 1,3-dicarbonyls 1, aldehydes 2, and allylic, propargylic or benzylic halides 3 is described. It provides a regio-, chemo- and stereoselective one-pot access to α,γ-difunctionalized α-ketoesters and amides 4, bearing a quaternary center valuable for further synthetic transformations via ring-closing metathesis to give azaspiro systems found in bioactive natural products.

multi-component reaction - β-ketoesters - β-ketoamides - α,γ-difunctionalization - azaspiro derivatives

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General Experimental Procedure: To a solution of 1,3-dicarbonyl 1 (1 mmol) and DBU (3 mmol) in dry THF (8 mL) containing 10% dry MeOH in the case of β-ketoesters and MeOH alone (8 mL) in the case of β-ketoamides was added the corresponding aldehyde 2 (1 mmol) and halide 3 (2 mmol). The resulting solution was stirred under nitrogen at r.t. or under reflux for the indicated time (Table [1] ). After completion and evaporation of most of the solvent under reduced pressure, water (50 mL) was added to the oily residue. Extraction with Et₂O (3 × 40 mL) followed by successive washing with distilled water (2 × 20 mL) and brine (20 mL) gave, after drying (MgSO₄) and evaporation of the solvent, the crude compounds which were purified by flash chromatography on silica gel.

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