An electrocatalytic approach to discovering new synthetic transformations

项目摘要 烯烃是生物活性化合物中普遍存在的基团，也是生物活性化合物中用途广泛的基元 有机合成由于其丰富的反应性。而烯烃传统上是由 历史悠久的反应，如Wittig烯化、格拉布斯歧化和消除反应， 这种化学反应在很大程度上依赖于预官能化起始材料的使用。而当 这些方法提供了有利的工具，阻碍了精细化学合成的步骤经济 从原料中分离出来，而且往往不适应后期功能化。因此，温和的 在有机合成中，烷烃减饱和的方法备受追捧。虽然 最近已经开发了几种方法来转化丰富的官能团，如 C-H键，这些方法通常需要使用贵重的过渡金属 催化剂，周转率低，或需要化学计量比的氧化剂。 在这个方案中，我们提出了一种新的、实用的方法来合成烯烃。 容易获得的自由基前体。具体地说，我们建议进一步发展 硫自由基阳离子捕获碳心自由基，原位生成硫离子。这些 中间体将能够发生消除反应来提供烯烃。这 该方法将利用阳极上的两个氧化事件来产生一对反应性催化剂 自由基中间体-瞬时的碳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性质，如较长的寿命、反应性 碳中心自由基的捕获和生成的烷基硫的亲电性 离子将使富有成效的转变成为可能。这种自由基-极性交叉反应将提供一种 一种避免使用化学计量活化的电化学烷烃脱饱和法 其他方法通常使用的基团和刺激性氧化剂。该项目有三个具体目标： 1)在脱羧化的背景下建立硫自由基阳离子的概念验证反应性 羧酸的去饱和化，以及2)通过以下途径将这种反应性扩展到简单烷烃 氢原子抽象。为了达到第二个目标，我们将调查一些已知的 新的电化学介体作为C-H活化的H原子受体。最后，3)这 方法将用于亲核取代，以使用 随手可得的亲核分子。

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.