Base Metal Catalyzed Alkene Cycloadditions for Cyclobutane Synthesis

描述（由申请人提供）：小分子显示的生物活性是它们与分子受体三维相互作用的结果。因此，在生物活性化合物中常见的立体定义单元的组装对合成化学在健康相关研究中的重要性至关重要。环丁烷存在于许多具有生物活性的化合物中，是一种优秀的四碳合成材料。为了充分发挥含环丁烷化合物的潜力，建立通用的、高效的、最终具有对映选择性的环丁烷化合物构建途径至关重要。目前，可用于合成四元碳环的方法与几十年前的五元和六元类似物的方法相比是有限的。这抑制了对这种普遍存在于生物学相关分子中的基序的探索。本研究的长期目标是发展一般贱金属催化的环加成反应，这将为环丁烷的合成和复杂生物活性化合物的构建提供快速途径。

DESCRIPTION (provided by applicant): The biological activity displayed by small molecules is the result of their three dimensional interactions with molecular receptors. Therefore, the assembly of stereodefined units commonly found in bioactive compounds is central to the importance of synthetic chemistry in health-related research. Cyclobutanes are found in numerous compounds that display bioactivity and serve as excellent four-carbon synthetic building blocks. In order for the full potential of cyclobutane containing compounds to be realized, establishing general and efficient, and ultimately enantioselective, routes to their construction is crucial. Currently, available methods for the synthesis of four-membered carbocycles are limited as compared to decades-old routes to five- and six-membered analogs. This inhibits the exploration of this motif that is prevalent in biologically relevant molecules. Te long-term goal of this research is the development of general base-metal-catalyzed cycloaddition reactions that will provide rapid access to cyclobutanes for use as synthetic building blocks and in the construction of complex bioactive compounds. This research is based on the central hypothesis that base-metal catalysts offer unique advantages when coupled with redox-active ligands in order to facilitate transformations that are typically relegated to noble metal catalysis or are otherwise not feasible. Focus centers on three specific aims: (1) Devevlop general methods for the Fe-catalyzed intramolecular [2+2] cycloaddition of unactivated alkenes; (2) Develop general methods for the Fe-catalyzed intermolecular [2+2] cycloaddition of unactivated alkenes; and (3) Develop chiral catalysts for enantioselective base metal-catalyzed [2+2] cycloadditions. Our results will have a significant impact by providing rapid access to the largely untapped bioactivity-rich chemical space occupied by cyclobutanes and their derivatives while simultaneously expanding the understanding and utility of base metal catalysis for use in future reaction development.