Synthetic studies on bafilomycin A1: first formation of the 16-membered macrolide via an intramolecular Stille reaction

The 16-membered macrolide formation of a bafilomycin A1 synthesis intermediate showed to be very difficult to achieve via an intramolecular Stille reaction. Complex reactions were observed, depending on the nature of the palladium source, ligand, solvent and reaction conditions. Unexpected reactions of the 2-furyl group transfer of trifurylphosphine were observed on the vinylic iodide and (or) the vinylstannane. Best conditions were found with Pd2(dba)3/AsPh3/i-Pr2NEt in DMF, at 40 °C, to afford the desired macrocycle in 28% yield (33% corrected), the structure of which was definitely confirmed by chemical filiation.