Total Synthesis of Elaiolide Using a Copper(I)-Promoted Stille Cyclodimerization Reaction

The 16-membered macrodiolide elaiolide (2) has been prepared in 20 steps from the ketone (S)-8 in 9.3% overall yield with a diastereoselectivity of 76%. Key steps included the copper(I) thiophene-2-carboxylate promoted cyclodimerization of the vinyl stannane 3 to give the C2-symmetric macrocycle 16 in 80% yield and the two-directional aldol coupling of the macrocyclic diketone 17 with aldehyde 5. Most of the stereocenters in the macrocyclic precursor 3 were constructed using boron aldol methodology developed in this laboratory.