Transition Metal Catalyzed Reductive Carbene Transfer Reactions

项目摘要/摘要 卡宾是能够进行环加成，键插入， 重排和偶联反应。开发卡宾转移催化变体的先前努力 反应主要集中在重氮烷的使用上。这种方法的主要限制是 重氮烷烃一般必须用吸电子基团或芳基稳定，以避免 氮气的自发、放热消除。这项计划的首要目标是研究 使用易得的GEM-二卤试剂的过渡金属催化的还原卡宾转移反应 作为非稳定卡宾的前体。可以使用化学还原剂实现催化周转，例如 作为金属粉末。或者，使用光氧化还原或电催化还原使这些反应 与新兴的流量合成平台兼容。 将开发更广泛的催化环加成反应。一个特别的焦点将是 生成奇元环，这是传统的热周环难以获得的 流程。例如，过渡金属催化将允许西蒙斯-史密斯反应的电流限制。 有待解决的问题，例如二甲基环丙烷、螺环丙烷和亚甲基环丙烷的对映选择性合成。 亚乙烯和1，3-二烯的不对称[4+1]-环加成反应生成复杂的环戊烯 衍生品。最后，将开发三组分的[n+m+1]-环加成反应来合成5-和 七元碳环和杂环。其中一些反应将使用双核金属催化剂， 它们提供了一个独特的活性中心环境来调节卡宾和亚乙烯转移反应。 过渡金属催化的乙烯对烯烃的加成反应也可以转变为非环加成反应。 在环关闭之前截取金属环中间体的途径。反应设计的基础是 促进这些金属环的β-X消除或转金属反应。基于这一概念，小说 碳-碳偶联反应将用于手性醇和胺产品的合成。 本项目中开发的催化概念将通过提供对复合体的访问来影响人类健康 富含C(SP3)的框架，可结合到生物探针和治疗中。

Project Summary/Abstract Carbenes are versatile reactive intermediates capable of engaging in cycloaddition, bond insertion, rearrangement, and coupling reactions. Previous efforts to develop catalytic variants of carbene transfer reactions have largely focused on the use of diazoalkanes. The primary limitation of this approach is that diazoalkanes generally must be stabilized with electron-withdrawing or aryl groups in order to avoid the spontaneous, exothermic elimination of dinitrogen gas. The overarching goal of this program is to study transition metal catalyzed reductive carbene transfer reactions that use readily available gem-dihalo reagents as precursors to non-stabilized carbenes. Catalytic turnover can be achieved using chemical reductants, such as metal powders. Alternatively, the use of photoredox or electrocatalytic reduction makes these reactions compatible with emerging flow synthesis platforms. A broad scope of catalytic cycloaddition reactions will be developed. A particular focus will be on generating odd-membered rings, which are challenging to access by conventional thermal pericyclic processes. For example, transition metal catalysis will allow current limitations of the Simmons–Smith reaction to be addressed, such as the enantioselective synthesis of dimethyl-, spiro-, and methylenecyclopropanes. Asymmetric [4 + 1]-cycloadditions of vinylidenes and 1,3-dienes will generate complex cyclopentene derivatives. Finally, three-component [n + m + 1]-cycloadditions will be developed for the synthesis of five- and seven-membered carbocycles and heterocycles. Some of these reactions will use dinuclear metal catalysts, which provide a unique active site environment to mediate carbene and vinylidene transfer reactions. Transition metal-catalyzed additions of vinylidenes to alkenes can also be diverted to non-cycloaddition pathways by intercepting metalacyclic intermediates prior to ring closure. Reaction design is based on promoting β-X elimination or transmetalation reactions of these metalacycles. Based on this concept, novel carbon–carbon coupling reactions will be developed for the synthesis of chiral alcohol and amine products. The catalysis concepts developed in this project will impact human health by providing access to complex C(sp3)-rich frameworks that can be incorporated into biological probes and therapeutics.