The key aetheramide A intermediate with the natural (R,R,R) configuration along with the one having the unnatural (R,S,R) configuration was synthesized. The synthesis of both stereoisomers was accomplished by Suzuki coupling of two advanced chiral building blocks: (R,R)- and (R,S)-vinylboronates and an (R)-iodoalkene.
The former was prepared from (R)-mandelic acid, and the latter was prepared by enantioselective allylation of 3-iodoacrylaldehyde.