Transition Metal Catalyzed Reductive Carbene Transfer Reactions

项目总结/摘要 卡宾是多用途的反应性中间体，能够参与环加成，键插入， 重排和偶联反应。先前开发卡宾转移催化变体的努力 反应主要集中于使用重氮烷。这种方法的主要局限性是， 重氮烷烃通常必须用吸电子或芳基稳定，以避免 自发的、放热的消除二氮气体。该计划的首要目标是研究 使用容易获得的偕二卤代试剂的过渡金属催化的还原卡宾转移反应 作为不稳定卡宾的前体。催化周转可以使用化学还原剂来实现，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 与新兴的流动合成平台兼容。 将开发范围广泛的催化环加成反应。一个特别的重点将是 产生奇数元环，这是具有挑战性的访问由传统的热周环 流程.例如，过渡金属催化将允许Simmons-Smith反应的电流限制 例如二甲基-、螺环-和亚甲基环丙烷的对映选择性合成。 亚乙烯基和1，3-二烯的不对称[4 + 1]-环加成反应将生成复杂的环戊烯 衍生物.最后，三组分[n + m + 1]-环加成反应将被开发用于合成五个-和 七元碳环和杂环。这些反应中的一些将使用双核金属催化剂， 其提供独特的活性位点环境以介导卡宾和亚乙烯基转移反应。 过渡金属催化的亚乙烯基与烯烃的加成反应也可以转向非环加成反应 通过在环闭合之前拦截金属非环中间体的途径。反应设计基于 促进这些杂环的β-X消除或金属转移反应。基于这一理念，小说 碳-碳偶联反应将被开发用于手性醇和胺产物的合成。 该项目中开发的催化概念将通过提供复杂的催化剂来影响人类健康。 C（sp3）丰富的框架，可以纳入生物探针和治疗。

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.