An electrocatalytic approach to discovering new synthetic transformations

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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.