Total Synthesis of Limaol

A nonthermodynamic array of four skipped methylene substituents on the hydrophobic tail renders limaol, a C40-polyketide of marine origin, unique in structural terms. This conspicuous segment was assembled by a two-directional approach and finally coupled to the polyether domain by an allyl/alkenyl Stille reaction under neutral conditions. The core region itself was prepared via a 3,3′-dibromo-BINOL-catalyzed asymmetric propargylation, a gold-catalyzed spirocyclization, and introduction of the southern sector via substrate-controlled allylation as the key steps.