An electrocatalytic approach to discovering new synthetic transformations

发现新合成转化的电催化方法

• 批准号: 10406065
• 负责人: Song Lin
• 金额: $ 12.94万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406065
• 关键词: Alkanes; Alkenes; Anodes; Carbon; Carboxylic Acids; Cations; Chemistry; Development; Event; Generations; Hydrogen; Hydrogen Bonding; In Situ; Ions; Mediator of activation protein; Methods; Organic Chemistry; Organic Synthesis; Oxidants; Property; Reaction; Sulfur; Transition Elements; catalyst; chemical synthesis; functional group; novel; nucleophilic substitution; tool

Project Summary Alkenes are prevalent groups in bioactive compounds and are also versatile motifs in organic synthesis owing to their rich reactivity. While alkenes have traditionally been prepared by venerable reactions like the Wittig olefination, Grubbs metathesis, and elimination reactions, much of this chemistry has relied on the use of pre-functionalized starting materials. While providing enabling tools, these approaches hinder the step economy of fine chemical synthesis from feedstocks and are often not amenable to late-stage functionalization. As a result, mild methods for the desaturation of alkanes are highly sought after in organic synthesis. Although several methods have recently been developed for transforming abundant functional groups like C–H bonds to alkenes, these approaches typically require the use of precious transition metal catalysts, suffer from poor turnover numbers, or require stoichiometric oxidants. In this proposal, we present a novel and practical method for the synthesis of alkenes from readily available radical precursors. Specifically, we propose to further develop the proclivity of sulfur radical cations to trap carbon centered radicals to generate sulfonium ions in situ. These intermediates will be capable of undergoing an elimination reaction to furnish alkenes. This approach will leverage two oxidative events at an anode to generate a pair of reactive catalytic radical intermediates—a transient carbon-centered radical and a persistent sulfur radical cation. The innate properties of sulfur radical cations such as their relatively long lifetime, reactivity towards capturing carbon-centered radicals, and electrophilicity of the resultant alkyl sulfonium ions will enable productive transformations. This radical-polar crossover reaction will provide an electrochemical alkane desaturation method that avoids the use of stoichiometric activating groups and harsh oxidants typically used by other methods. This project has three specific aims: 1) establish proof-of-concept reactivity of sulfur radical cations in the context of decarboxylative desaturation of carboxylic acids, and 2) expansion of this reactivity to simple alkanes through hydrogen atom abstraction. To achieve the second aim, we will investigate a number of known and new electrochemical mediators as H-atom acceptors for C–H activation. Lastly, 3) this method will be used for nucleophilic substitution to rapidly access a host of functionalities using readily available nucleophiles.

项目摘要 烯烃是生物活性化合物中普遍的组，也是多功能基序 有机合成由于其丰富的反应性。传统上，烯烃是由 诸如Wittig烯烃，grubbs归化和消除反应等尊贵的反应， 这种化学的大部分已经缓解了使用预官能化的原材料。尽管 这些方法提供允许的工具，阻碍了精细化学合成的步骤经济 来自原料，通常不适合晚期功能。结果，中间 在有机合成中，高度追捧了烷烃去饱和的方法。虽然 最近已经开发了几种方法来转换丰富的官能团 C – H键与烯烃，这些方法通常需要使用宝贵的过渡金属 催化剂，营业额数不良或需要化学计量氧化。 在此提案中，我们提出了一种新颖而实用的方法，用于合成烯烃 容易获得的根治性前体。特别是，我们建议进一步发展 硫基自由基阳离子以捕获碳中心的自由基，以原位产生磺基离子。这些 中间体将能够进行消除反应以提供烷烃。 方法将利用阳极处的两个氧化事件来产生一对反应性催化 自由基中间体 - 瞬时以碳为中心的自由基和持续的硫自由基阳离子。 硫自由基阳离子的先天特性，例如它们的相对长寿命，反应性 捕获以碳为中心的自由基和所得烷基磺硫的亲电性 离子将实现生产转换。这种自由基的跨界反应将提供 避免使用化学计量激活的电化学烷烃宗教法 通常由其他方法使用的组和HARMSH氧化剂。该项目具有三个特定的目标： 1）在脱羧的背景下，建立硫基自由基阳离子的反应反应性 羧酸的去饱和度，以及2）通过 氢原子抽象。为了实现第二个目标，我们将研究许多已知的 以及新的电化学介质作为C – H激活的H原子受体。最后，3）这个 方法将用于使用核类似物取代，以快速使用 容易获得的亲核试剂。