Stereoselective Synthesis of a Highly Oxygenated δ-Lactone Related to the Core Structure of (–)-Enterocin

Dedicated to Professor Dieter Enders on the occasion of his 70^th birthday

Abstract

The title compound was prepared in a concise route starting from an appropriately protected (S)-glyceraldehyde. A highly diastereoselective (d.r. >95:5) Mukaiyama aldol reaction of an acetoacetate-derived silyl enol ether served as the initial step of the synthetic sequence. It was found that protection of the glyceraldehyde as a butane-2,3-dione acetal is required to achieve the desired diastereoselectivity. Upon lactonization, a Tsuji–Trost allylation and a subsequent one-pot reaction cascade including an ozonolysis and an α-hydroxylation gave dia­stereoselective access to the desired α-hydroxy-β-oxo-δ-lactone. Alternative synthetic approaches are discussed and proof for the configuration of the product is presented.

Key words

aldol reaction - diastereoselectivity - natural product synthesis - oxygenation - polyketides

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