Synthesis of the C(1)–C(13) Fragment of Leiodermatolide via Hydrogen-Mediated C–C Bond Formation

The C(1)–C(13) fragment of the antimitotic marine macrolide leiodermatolide is prepared in seven steps via hydrogenative and transfer-hydrogenative reductive C–C couplings. A hydrogen-mediated reductive coupling of acetylene with a Roche-type aldehyde is used to construct C(7)–C(13). A 2-propanol-mediated reductive coupling of allyl acetate with (<i>E</i>)-2-methylbut-2-enal at a low loading of iridium (1 mol %) is used to construct C(1)–C(6), which is converted to an allylsilane using Oestereich’s copper-catalyzed allylic substitution of Si–Zn reagents. The union of the C(1)–C(6) and C(7)–C(13) fragments is achieved via stereoselective Sakurai allylation