Total Synthesis of (−)-Gambierol FuwaHaruhiko KainumaNoriko TachibanaKazuo SasakiMakoto 2002 The first total synthesis of (−)-gambierol (<b>1</b>), a marine polycyclic ether toxin, has been achieved. Key features of the successful synthesis include (1) a convergent union of the ABC and EFGH ring fragments (<b>5</b> and <b>6</b>, respectively) via our developed <i>B</i>-alkyl Suzuki−Miyaura cross-coupling strategy leading to the octacyclic polyether core <b>4</b> and (2) a late-stage introduction of the sensitive triene side chain by use of Pd(PPh<sub>3</sub>)<sub>4</sub>/CuCl/LiCl-promoted Stille coupling. The ABC ring fragment <b>5</b> was synthesized in a linear manner (B → AB → ABC), wherein the A ring was formed by intramolecular hetero-Michael reaction and the C ring was constructed via 6-endo cyclization of hydroxy epoxide <b>7</b>. An improved synthetic entry to the EFGH ring fragment <b>6</b> is also described, in which SmI<sub>2</sub>-induced reductive cyclization methodology was applied to the stereoselective construction of the F and H rings, leading to <b>6</b> with remarkable overall efficiency. Stereoselective hydroboration of <b>5</b> and subsequent Suzuki−Miyaura coupling with <b>6</b> provided endocyclic enol ether <b>45</b> in high yield, which was then converted to octacyclic polyether core <b>4</b>. Careful choice of the global deprotection stage was a key element for the successful total synthesis. Functionalization of the H ring and global desilylation gave (<i>Z</i>)-vinyl bromide <b>2</b>. Finally, cross-coupling of <b>2</b> with (<i>Z)</i>-vinyl stannane <b>3</b> under Corey's Pd(PPh<sub>3</sub>)<sub>4</sub>/CuCl/LiCl-promoted Stille conditions completed the total synthesis of (−)-gambierol (<b>1</b>).