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.

项目概要 烯烃是生物活性化合物中的普遍基团，也是生物活性化合物中的通用基序 由于其丰富的反应活性，有机合成传统上是通过以下方法制备的。 古老的反应，如维蒂希烯化反应、格拉布斯复分解反应和消除反应， 这种化学反应大部分依赖于预官能化起始材料的使用。 这些方法提供了有利的工具，但阻碍了精细化学合成的步骤经济性 来自原料，通常不适合后期功能化，因此性质温和。 烷烃去饱和的方法在有机合成中受到高度追捧。 最近开发了几种方法来转化丰富的官能团，例如 C-H 键与烯烃结合，这些方法通常需要使用贵重的过渡金属 催化剂，数量周转率低，或需要化学计量的氧化剂。 在本提案中，我们提出了一种新颖实用的方法来合成烯烃 具体来说，我们建议进一步发展容易获得的激进前体。 硫自由基阳离子捕获以碳为中心的自由基，从而原位生成锍离子。 中间体将能够进行消除反应以提供烯烃。 该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——瞬时的碳中心自由基和持久的硫自由基阳离子。 硫自由基阳离子的固有特性，例如相对较长的寿命、反应性 捕获以碳为中心的自由基，以及所得烷基锍的亲电性 离子将实现富有成效的转变。 避免使用化学计量活化的电化学烷烃去饱和方法 该项目具有三个具体目标： 1) 在脱羧的背景下建立硫自由基阳离子反应性的概念验证 羧酸的去饱和，以及 2) 通过以下方式将这种反应性扩展到简单的烷烃 为了实现第二个目标，我们将研究一些已知的氢原子。 以及新的电化学介体作为 C-H 活化的 H 原子受体最后，3）这个。 方法将用于亲核取代，以快速访问一系列功能 容易获得的亲核试剂。