Sigma-Aldrich Chemistry Symposium: Midwest Region
The activation of acyl C–O and C–C bonds: discovery, mechanism and application in synthesis
The metal-mediated activation of bonds to carbon has changed the way organic chemists approach chemical synthesis. This seminar will tell two stories from our lab in the area of activating the carbon acyl bond. The first story describes our sterically-controlled arene acylation with esters via iridium catalysis. This transformation provides complementary selectivity to the electronically controlled Friedel-Crafts acylation, and allows direct access to new substituted benzophenones. I will present our discovery of this process, and investigation into the synthetic utility of the reaction through a study of the scope of both arene and ester components, culminating in the concise synthesis of the potent anti-cancer/anti-mitotic agent hydroxyphenstatin. Our mechanistic data indicates a unique reaction mechanism that integrates metal mediated acyl C–O activation with arene C–H activation with a single iridium catalyst. The second story describes our development of the activation of the acyl bond of cyanoformamides for additions across alkenes. Our mechanistic work elucidated the role of Lewis base and Lewis acid additives in the process and paved the way for its application in alkaloid synthesis.