Synthesis of nectriapyrone

A totally synthetic route to the antibacterial fungal metabolite nectriapyrone ( 1 ) has been achieved by condensation of methylmalonyl dichloride with ethyl trans ‐4‐methyl‐3‐oxo‐4‐hexenoate followed by hydrolysis, decarboxylation, and methylation of the resulting 3‐methyl‐4‐hydroxy‐5‐carbethoxy‐6‐( trans ‐1‐methyl‐1‐propenyl)‐2‐pyrone. Exploration of an alternate scheme involving the dehydrogenation of 6‐substituted‐4‐methoxy‐5,6‐dihydro‐2‐pyrones, prepared by Reformatsky reaction of ethyl γ‐bromo‐β‐methoxycrotonate with various aldehydes, was abandoned since it did not appear to have general applicability to the preparation of nectriapyrone and its analogs.