Exploration of Oxetane Formation via Swern Annulation on a Model System for the Synthesis of Curvularol

Abstract

The Swern annulation is proposed as a new strategy to form highly substituted oxetanes on lactones. This approach is explored on a model system as part of efforts toward the total synthesis of curvularol, a structurally complex natural product with a rearranged trichothecene skeleton. Synthesizing the precursor of the Swern annulation via Giese addition was unproductive, which was hypothesized to be due to steric hindrance at the β-position of the disubstituted Michael Acceptor. These results directed subsequent efforts to synthesize a di- activated model system with an electron-withdrawing group at the α-position. While these endeavors faced challenges, promising avenues remain for synthesizing the di-activated model system. Lastly, the substrate scope of the Swern annulation was explored using a five-membered model system, whose photoinduced addition of isopropyl alcohol is known. With this photoadduct, oxetane formation via Swern annulation was observed. In closing, potential approaches for future study are proposed.