'Anomalous' Ozonolysis of Cyclic Allylic Alcohols: Mechanism and Synthetic Utility

摘要

The anomalous ozonolysis of cyclic allylic alcohols has been investigated. A distinct mechanistic pathway has been elucidated on the basis of the structure determination of the 1,2,4-trioxane intermediate. The reaction is the basis of a new and concise method for the incorporation of isotopic carbon atoms as well as alkyl and aryl substituents at the α-position of cyclic enones. The utility of this method for the incorporation of a radiolabel at the C-2 position of steroids was demonstrated by the preparation of ~(14)C-labeled 11-ketotigogenin 14, a component of a cholesterol absorption inhibitor in clinical development. Details of this synthesis will be forthcoming.