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

本合作建议的重点是建立一种基于配对电解的烯烃加氢功能化的新策略。氢氯化、氢氟化和氢氰化反应是经典的合成转化反应，在有机合成和药物化学中有着广泛的应用。这类反应的传统方法使用丰富的无机酸（HX; X = F, Cl, Br， CN等），但通常在苛刻的条件下进行，化学选择性有限。近年来，金属氢化物介导的氢原子转移被创造性地应用于烯烃在温和条件下的自由基加氢功能化。然而，这些体系的特点是在底物上添加一对[H -]和[X+]等价物，因此仍然依赖于化学计量自由基前体，如氢硅烷和亲电（伪）卤素源。在本提案中，我们的目标是提出一种新的催化策略，即非氧化还原配对电催化，利用现成的矿物酸（HX）建立高效，选择性和可持续的加氢功能化反应。具体来说，两个催化循环将在阴极和阳极平行进行，在与烯烃反应之前，每个循环都会产生一个金属结合的自由基前体（M1-H和M2-X）。总体目标包括：1。在加氢氯化法中建立非氧化还原配对电催化。我们的目标是使用一对Co（阴极，+ H+）和Mn（阳极，+ Cl-）配合物分别作为H原子转移和Cl原子转移催化剂来实现烯烃的氢氯化反应。2. 非氧化还原配对电催化的机理研究。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。该机制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加氢功能化反应。我们将把同样的催化策略扩展到其他反应，如氢氟化、氢氰化和氢硫氰化。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发展教育机会。在过去的几年里，有机化学学界对电化学的研究兴趣重新燃起。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探索。这一建议将提出一种新的催化策略，阐述了典型的配对电解。我们将这种策略命名为非氧化还原配对电催化，它将以收敛的方式结合一对阴极和阳极催化循环，为具有挑战性的氧化还原中性转化提供新的解决方案。对协同电催化机理的理解也将推进氧化还原反应和元催化的基础知识

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