Chapter 6 - The Development of Strategies and Tactics Toward the Pseudopterosin Natural Products: Ileabethoxazole As a Platform for Target-Inspired Discovery

Abstract

Abstract The target-inspired presentation describes the evolution of important strategies and tactics for the enantiocontrolled synthesis of pseudopterosin aglycones. A detailed discussion of the development of the first synthesis of ileabethoxazole is featured. The synthesis strategy contributes to significant discoveries of new reactivity and reactions. A preparation of 1,1-disubstituted allenes is illustrated using propargylic stannanes in modified Stille cross-coupling reactions. Site-selective palladium insertions facilitate a general pathway for regiocontrolled preparations of disubstituted and trisubstituted 1,3-oxazoles. The first report of the halogen dance reaction in 1,3-oxazoles is described. A novel iron-mediated [2+2+1] carbocyclization yields substituted cyclopentenones under mild conditions. These reactions proceed via the reactivity of a previously unknown, three-membered iron metallacycle. This reaction profile has been examined through mechanistic studies and density functional theory calculations. A chiral H 8 -BINAP ligand is employed in the preparation of hydridocopper reagent for 1,4-conjugate additions with improved stereoselectivity in asymmetric reductions of indenones.