Efficient Asymmetric Synthesis of Long‐Chain Polyketides Containing up to Ten Contiguous Stereogenic Centres by Double Chain Elongation

Abstract

AbstractThe 2,3‐anti‐3,4‐syn‐stereotriad (1Z,2S,3R,4S)‐1‐ethylidene‐2,4‐dimethyl‐3‐[(1S)‐1‐phenylethoxy]‐5‐oxopent‐1‐yl isobutyrate {(–)‐8, obtained in a one‐pot operation from the trimethylsilyl (Z)‐enol ether derived from pentan‐3‐one and(1E,3Z)‐1[(1S)‐phenylethoxy]‐2‐methylpenta‐1,3‐dien‐3‐ylisobutyrate through SO2 umpolung} contains an ethyl ketone moiety that undergoes diastereoselective cross‐aldol reactions with acetaldehyde. After subsequent reductions, various diastereomeric stereohexads (polypropionate fragments containing six contiguous stereogenic centres) in which the (Z)‐enol isobutyrate units remained intact were obtained. After suitable protection, these were converted into their corresponding lithium (Z)‐enolates, which could react with isopropylidene D‐glyceraldehyde [(+)‐9] to give aldol products that were reduced to various stereodecads (polyketides with ten contiguous stereogenic centres). The disclosed chemistry represents a quick, asymmetric, diastereoselective andstereodivergent construction of long‐chain polyketides and analogues by a double‐chain‐elongation strategy.