Mechanisms of Cascade Reactions in the Syntheses of Camptothecin-Family Alkaloids: Intramolecular [4+ + 2] Reactions of N-Arylimidates and Alkynes

Abstract

The key steps of cascade reactions employed in the syntheses of camptothecin-family alkaloids by Fortunak and Yao are intramolecular aza-Diels-Alder (IADA) reactions between in situ generated N-arylimidates and alkynes. The efficiencies of the IADA reactions are different but not well-understood. DFT calculations shown here provide insights into these two IADA reactions and well-rationalize why hexaphenyloxodiphosphonium triflate (Hendrickson reagent) as an amide-activating reagent is superior to trimethyloxonium fluoroborate.