Base Metal Catalyzed Alkene Cycloadditions for Cyclobutane Synthesis

描述(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，生物活性化合物中常见的固定定义单元的组装对于合成化学在与健康相关的研究中的重要性至关重要。环丁烷存在于许多化合物中，这些化合物具有生物活性，是极好的四碳合成构件。为了充分发挥环丁烷类化合物的潜力，建立通向其构筑的通用、高效并最终具有对映选择性的路线是至关重要的。目前，与几十年前合成五元和六元类似物的路线相比，可用于合成四元碳环的方法有限。这抑制了对生物相关分子中普遍存在的这个基序的探索。这项研究的长期目标是开发一般的贱金属催化的环加成反应，这种反应将提供快速获得环丁烷的途径，用作合成构件和构建复杂的生物活性化合物。 这项研究基于一个中心假设，即贱金属催化剂在与氧化还原活性配体结合时具有独特的优势，以便促进通常属于贵金属催化或以其他方式不可行的转化。重点集中在三个具体目标上：(1)铁催化的未活化烯烃分子内[2+2]环加成反应的Devevlop通用方法；(2)开发铁催化的未活化烯烃分子间[2+2]环加成反应的通用方法；(3)开发手性催化剂用于对映选择性贱金属催化的[2+2]环加成反应。 我们的结果将产生重大影响，因为我们提供了快速进入环丁烷及其衍生物占据的大部分未开发的生物活性丰富的化学空间，同时扩大了对贱金属催化的理解和使用，用于未来的反应发展。

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.