Progress Toward the Total Synthesis of Curcusone C and Mechanistic Elucidation of an Unexpected Rearrangement

Citation

Lee, Chung Whan (2015) Progress Toward the Total Synthesis of Curcusone C and Mechanistic Elucidation of an Unexpected Rearrangement. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9J964C4. https://resolver.caltech.edu/CaltechTHESIS:05292015-143832701

Abstract

Curcusone C is tricyclic diterpenoid natural product isolated from Jatropha curcas that exhibits potent biological activity and features a 2,3,7,8- tetrahydroazulene-1,4-dione moiety. Herein, we describe a synthetic approach toward ent-curcusone C. Construction of the tricyclic scaffold of ent-curcusone C is achieved from a cyclopentenol boronate and a vinyl bromide, which was synthesized from (S)-perillaldehyde. Suzuki coupling of the two precursors furnished a dieneol, which was converted to a diazoester via transesterification followed by diazo transfer reaction. A divinylcyclopropane was synthesized from the diazoester by intramolecular cyclopropanation and subsequent Kauffmann olefination. The tricyclic core of ent-curcusone C was accomplished by divinylcyclopropane rearrangement, which was initiated by reduction of the lactone moiety.

We discovered an unexpected rearrangement during the course of our investigation toward the synthesis of curcusone C. Surprisingly, a silyl enol ether was converted to a complex tetracyclic compound under mild heating conditions. The transformation was elucidated as a unique reaction cascade of [3,3] Cope rearrangement, [1,5] silyl migration, Ireland–Claisen rearrangement, retro Claisen rearrangement, and [1,5] silyl migration by computational and experimental efforts.

Additionally, our work on the development of a bis(phosphine) copper catalyst for the asymmetric alkylation of 3-Bromooxindoles with α-arylated malonate esters is described. Versatile copper sources and chiral bis(phosphine) ligands were investigated.

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