Base Metal Catalyzed Alkene Cycloadditions for Cyclobutane Synthesis

贱金属催化烯烃环加成合成环丁烷

• 批准号: 8779921
• 负责人: Valerie Anne Schmidt
• 金额: $ 5.15万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8779921
• 关键词: Alkenes; Alkynes; Area; Biological; Biological Factors; Biology; Carbon; Catalysis; Chemicals; Chemistry; Complex; Coupled; Cyclization; Cyclobutanes; Development; Dimerization; Future; Goals; Health; Human; Hydrogenation; Iron; Ketones; Ligands; Metals; Methods; Molecular; Organic Synthesis; Outcome; Oxidation-Reduction; Pharmacologic Substance; Process; Public Health; Reaction; Research; Route; Science; Structure; Synthesis Chemistry; Therapeutic; Transition Elements; Work; analog; base; catalyst; chromophore; cycloaddition; diene; electronic structure; forging; improved; next generation; novel strategies; propadiene; public health relevance; pyridine; receptor; small molecule; success; tool

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.

描述（由申请人提供）：小分子显示的生物活性是其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立体定向单元的组装对于合成化学在健康相关研究中的重要性至关重要。环丁烷存在于许多化合物中，这些化合物显示出生物活性并作为优异的四碳合成结构单元。为了实现含环丁烷的化合物的全部潜力，建立通用且有效的且最终具有对映选择性的路线来构建它们是至关重要的。目前，与几十年前的五元和六元类似物的合成路线相比，合成四元碳环的可用方法是有限的。这抑制了在生物学相关分子中普遍存在的这种基序的探索。本研究的长期目标是发展一般的贱金属催化的环加成反应，这将提供快速获得环丁烷用作合成的结构单元，并在复杂的生物活性化合物的建设。 这项研究是基于中心的假设，贱金属催化剂提供独特的优势时，与氧化还原活性配体，以促进转化，通常被降级到贵金属催化或否则是不可行的。重点集中在三个具体目标：（1）开发铁催化未活化烯烃的分子内[2+2]环加成的一般方法;（2）开发铁催化未活化烯烃的分子间[2+2]环加成的一般方法;（3）开发用于不对称选择性贱金属催化[2+2]环加成的手性催化剂。 我们的研究结果将产生重大影响，通过提供快速进入环丁烷及其衍生物所占据的基本上未开发的生物活性丰富的化学空间，同时扩大对贱金属催化的理解和实用性，以用于未来的反应开发。