Allene cycloisomerization, epoxidation, and applications in total synthesis

Disclosed are studies on the structure and reactivity of allenes and spirodiepoxides (SDEs) and their application to synthesis. A novel ruthenium promoted cycloisomerization of γ-enallenes to cyclopentenes was discovered. The effects of solvent, oxidant, and substrate structure on the stereoselectivity of SDE formation from 1,3-disubstituted and trisubstituted allenes were evaluated. A computational model was advanced for the rationalization of observed selectivity in such formations. The known acid instability of SDEs was exploited to effect a designed rearrangement of β-silyl SDE to an α-hydroxy enone. Silyl-substituted SDEs were utilized to give carbinol substituted heterocycles with excellent ee, α-hydroxy enones, as well as α,β-dihydroxy olefins. A silyl-SDE approach was used to accomplish a short and efficient total synthesis of the natural product, epi-citreodiol. A de novo synthesis of the anticancer natural product jaspine B was also achieved using a SDE-based approach.Ph. D.Includes bibliographical referencesIncludes vitaby Joseph Ryan Cusic