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，并且也是生物活性化合物中的通用基序。 有机合成由于其丰富的反应活性。虽然烯烃传统上是通过以下方法制备的： 古老的反应，如维蒂希烯化，格拉布斯复分解，和消除反应， 这种化学方法的大部分依赖于使用预官能化的起始材料。而 这些方法提供了使能工具，阻碍了精细化学品合成的分步经济 并且通常不适于后期官能化。因此，轻度 在有机合成中，对烷烃去饱和的方法有很高的要求。虽然 最近已经开发了几种方法来转化大量的官能团， C-H键连接到烯烃上，这些方法通常需要使用贵过渡金属 催化剂的转化率低，或者需要化学计量的氧化剂。 在这个提议中，我们提出了一种新的和实用的方法来合成烯烃， 容易获得的自由基前体。具体而言，我们建议进一步发展 硫自由基阳离子捕获碳中心自由基以原位产生锍离子。这些 中间体将能够进行消除反应以提供烯烃。这 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剂， 自由基中间体--一个短暂的碳中心自由基和一个持久的硫自由基阳离子。 硫自由基阳离子的固有性质，如它们相对较长的寿命、反应性 对捕获碳中心的自由基，和亲电性的所得烷基锍 离子将实现富有成效的转变。这种自由基-极性交叉反应将提供 避免使用化学计量活化的电化学烷烃去饱和方法 基团和其他方法通常使用的苛刻氧化剂。该项目有三个具体目标： 1)在脱羧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，和2）通过以下方式将这种反应性扩展到简单烷烃： 氢原子抽象。为了实现第二个目标，我们将研究一些已知的 和新的电化学介体作为H原子受体用于C-H活化。（3）这个 方法将用于亲核取代，以快速获得大量的功能，使用 容易获得的亲核试剂。

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.