Intramolecular Metal-Catalyzed Alkene (2+2}Cycloaddition

University Of Texas Austin, Austin TX

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Abstract

DESCRIPTION: (provided by applicant) Despite a wealth of research pertaining to metal catalyzed cycloadditions, to date, there are no reports of metal catalysts for intramolecular alkene (2+2)cycloaddition. We herewith describe the first metal catalyst for intramolecular cyclobutanation. This methodology allows for facile assembly of bicyclo(3.2.0)heptane ring systems. Related photochemical processes generally exhibit poor levels of stereoselectivity and are inefficient for acyclic substrates due to quenching of the excited state via alkene isomerization. In contrast, our metal catalyst for alkene (2+2)cycloaddition is viable for acyclic precursors and all cycloadducts are obtained as single stereoisomers. This methodology will be utilized in a general synthetic approach to members of the bourbonane and spatane families of natural products. Certain members of the spatane family strongly inhibit cell division in human melanoma and 224C astrocytoma neoplastic cell lines. Spatol's antimitotic activity is attributed to inhibition of microtubule assembly. Finally, strategies for development of enantioselective variants of this methodology are outlined.