Synthetic studies on des ‐thiomethyllooekeyolide A: Synthesis of the C 1 – C 16 fragment and investigation of cyclization strategies

Abstract Synthetic studies toward des ‐thiomethyllooekeyolide A ( 5 ), involving the convergent synthesis of the C 1 –C 16 polyketide fragment 25 and efforts toward construction of the pyran hemiketal motif, are described. Aldehyde 9 was prepared from butyraldehyde ( 11 ) via Brown crotylation and Mukaiyama aldol reaction as key steps. Vinyl iodide 10 was synthesized from 1,3‐propanediol ( 12 ), employing stereoselective epoxidation and ( Z )‐selective Wittig olefination as key transformations. Aldehyde 9 and vinyl iodide 10 were coupled via an NHK reaction, and the resulting alcohol 22 was converted to the C 1 –C 16 polyketide fragment 25 through a two‐step sequence. Ketone 25 was then subjected to various cyclization conditions to explore the formation of the pyran hemiketal motif.