Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

Abstract

The stereoselective synthesis of the (Z)-enamide fragment of chondrochloren (1) is described. A Buchwald-type coupling between amide 3 and (Z)-bromide 4 was used to generate the required fragment. The employed amide 3 comprising three chiral centers was obtained through a seven-step sequence starting from ᴅ-ribonic acid-1,4-lactone. The (Z)-vinyl bromide 4 is accessible in four steps from 4-hydroxybenzaldehyde. The pivotal cross coupling between both fragments was achieved after extensive experimentation with copper(I) iodide, K₂CO₃ and N,N'-dimethylethane-1,2-diamine.

Keywords: Z-enamide; cross coupling; myxobacteria; natural product; ribolactone.