Intramolecular Metal-Catalyzed Alkene (2+2}Cycloaddition

描述：（由申请人提供）尽管有大量的研究， 金属催化的环加成，迄今为止，没有金属催化的环加成的报道。 分子内烯烃（2+2）环加成反应的催化剂。我们在此描述 用于分子内环丁烷化的第一金属催化剂。这种方法 允许二环（3.2.0）庚烷环系统的容易组装。相关 光化学方法通常表现出较差的立体选择性水平， 由于激发态的淬灭， 通过烯烃异构化。相比之下，我们的烯烃金属催化剂 （2+2）环加成对于无环前体是可行的，并且所有环加成物都是 作为单一立体异构体获得。该方法将用于 合成的一般方法的成员的波旁烷和spatane家庭的 天然产品。spatane家族的某些成员强烈抑制细胞 在人黑素瘤和224C星形细胞瘤肿瘤细胞系中的分裂。斯帕托尔 抗有丝分裂活性归因于微管组装的抑制。 最后，开发这种对映体选择性变体的策略 方法概述。

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.