A Shimizu Non‐Aldol Approach to the Formal Total Synthesis of Palmerolide A

A formal total synthesis of palmerolide A has been accomplished by assembling three fragments by means of successive Julia–Kocienski olefination, Yamaguchi esterification, and ring‐closing metathesis (RCM). Our initial efforts to combine the first two fragments through a Julia–Kocienski reaction between a secondary sulfone and a ketone were not successful; nevertheless, it was feasible between a primary sulfone and aldehyde. Yamaguchi esterification with the third fragment then set the stage for a RCM reaction. Initial failure of the RCM with a PMB‐ether adjacent to the olefins and the difficulty in cleaving the PMB‐ether prompted us to change the choice of protecting groups, which then paved the way to the macrocyclic core of palmerolide A.