NSF-DFG Echem: Hydrofunctionalization by Non-redox Paired Electroatalysis

该合作建议的重点是建立一个新的策略的基础上成对电解烯烃的氢官能化。氢氯化、氢加成和氢氰化反应是经典的合成反应，在有机合成和药物化学中具有广泛的应用。传统的合成方法使用大量的无机酸（HX; X = F、Cl、Br、CN等），而不使用无机酸。但通常在苛刻的条件下进行，并表现出有限的化学选择性。近年来，金属氢化物介导的氢原子转移反应被创造性地用于在温和条件下实现烯烃的自由基氢官能化。然而，这些系统的特征在于将一对[H-]和[X+]等价物添加到基材中，因此仍然依赖于化学计量的自由基前体，例如氢硅烷和亲电子（假）卤素源。在这个提议中，我们的目标是提出一种新的催化策略，即非氧化还原成对电催化，使用容易获得的无机酸（HX）建立高效，选择性和可持续的氢官能化反应。具体地，两个催化循环将在阴极和阳极上并行操作，每个催化循环在与烯烃反应之前产生金属结合的自由基前体（M1-H和M2-X）。总体目标包括：1.氢氯化反应中非氧化还原成对电催化的建立。我们的目标是实现烯烃氢氯化使用一对钴（阴极，+ H+）和锰（阳极，+ Cl-）的配合物作为H-原子转移和Cl-原子转移催化剂，分别。2.非氧化还原成对电催化机理研究。我们将详细研究电化学催化剂活化和自由基加成过程的机理。机理信息将用于指导反应优化和策略扩展。3.策略扩展到其他电化学氢官能化反应。我们将把同样的催化策略扩展到其他反应，如氢加成、氢氰化和氢硫氰酸化。我们还将开发这些反应的对映选择性变体。4.为学生参与者和更广泛的社区提供教育机会。在过去的几年里，有机化学界对电化学的研究兴趣又有了新的增长。尽管电合成领域取得了重大进展，但电化学在合成创新方面的潜力尚未得到充分开发。这一建议将提出一种新的催化策略，阐述了典型的成对电解。这种策略，我们命名为非氧化还原成对电催化，将联合收割机结合一对阴极和阳极催化循环，以收敛的方式提供新的解决方案，具有挑战性的氧化还原中性转换。协同电催化机理的理解也将推进氧化还原反应和Meta氧化物的基础知识。

This collaborative proposal focuses on establishing a new strategy based on paired electrolysis for the hydrofunctionalization of alkenes. Hydrochlorination, hydrofluorination, and hydrocyanation reactions are classic synthetic transformations with broad applications in organic synthesis and medicinal chemistry. The traditional methods for such reactions use abundant inorganic acids (HX; X = F, Cl, Br, CN, etc.) but are often carried out under harsh conditions and exhibit limited chemoselectivity. Recently, metal-hydride-mediated hydrogen atom transfer has been creatively employed to achieve the radical hydrofunctionalization of alkenes under mild conditions. These systems, however, feature the addition of a pair of [H–] and [X+] equivalents to the substrate and thus remain reliant on stoichiometric radical precursors such as hydrosilanes and electrophilic (pseudo)halogen sources. In this proposal, we aim to advance a new catalytic strategy, namely non-redox paired electrocatalysis, to establish efficient, selective, and sustainable hydrofunctionalization reactions using readily available mineral acids (HX). Specifically, two catalytic cycles will operate in parallel on the cathode and anode, each generating a metal-bound radical precursor (M1–H and M2–X) prior to reaction with an alkene. The overall objectives include: 1. Establishing non-redox paired electrocatalysis in the context of hydrochlorination. We aim to achieve alkene hydrochlorination using a pair of Co (cathode, + H+) and Mn (anode, + Cl–) complexes as the H-atom transfer and Cl-atom transfer catalysts, respectively. 2. Mechanistic investigation of non-redox paired electrocatalysis. We will study in detail the mechanism of electrochemical catalyst activation and radical addition processes. The mechanistic information will be used to guide reaction optimization and strategy expansion. 3. Strategy expansion to other electrochemical hydrofunctionalization reactions. We will expand the same catalytic strategy towards other reactions such as hydrofluorination, hydrocyanation, and hydrothiocyanation. We will also develop enantioselective variants of these reactions. 4. Developing educational opportunities for student participants and the broader community. Intellectual Merit The past several years have seen a renewal of research interest in electrochemistry from the organic chemistry community. Despite significant advancements in the field of electrosynthesis, the potential of electrochemistry for synthetic innovation has yet to be fully explored. This proposal will advance a new catalytic strategy that elaborates on canonical paired electrolysis. This strategy, which we name non-redox paired electrocatalysis, will combine a pair of cathodic and anodic catalytic cycles in a convergent manner to provide new solutions to challenging redox-neutral transformations. The mechanistic understanding of synergistic electrocatalysis will also advance fundamental knowledge of redox reactions and meta