Intramolecular Metal-Catalyzed Alkene (2+2}Cycloaddition

分子内金属催化烯烃 (2 2}环加成

• 批准号: 6622782
• 负责人: MICHAEL J KRISCHE
• 金额: $ 18.75万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622782
• 关键词: alkenes; antimitotics; bicyclic compound; biological products; catalyst; chemical addition; cyclization; metals; stereochemistry

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.

描述：（由申请人提供）尽管有大量关于金属催化环添加的研究，但迄今为止，还没有金属催化环添加的报告