Nemoto David T, Bian Kang-Jie, Kao Shih-Chieh, West Julian G
Department of Chemistry, Rice University, 6100 Main St MS 602, Houston, TX 77005, USA.
Beilstein J Org Chem. 2023 Aug 15;19:1225-1233. doi: 10.3762/bjoc.19.90. eCollection 2023.
The place of alkyl radicals in organic chemistry has changed markedly over the last several decades, evolving from challenging-to-generate "uncontrollable" species prone to side reactions to versatile reactive intermediates enabling construction of myriad C-C and C-X bonds. This maturation of free radical chemistry has been enabled by several advances, including the proliferation of efficient radical generation methods, such as hydrogen atom transfer (HAT), alkene addition, and decarboxylation. At least as important has been innovation in radical functionalization methods, including radical-polar crossover (RPC), enabling these intermediates to be engaged in productive and efficient bond-forming steps. However, direct engagement of alkyl radicals remains challenging. Among these functionalization approaches, a bio-inspired mechanistic paradigm known as radical ligand transfer (RLT) has emerged as a particularly promising and versatile means of forming new bonds catalytically to alkyl radicals. This development has been driven by several key features of RLT catalysis, including the ability to form diverse bonds (including C-X, C-N, and C-S), the use of simple earth abundant element catalysts, and the intrinsic compatibility of this approach with varied radical generation methods, including HAT, radical addition, and decarboxylation. Here, we provide an overview of the evolution of RLT catalysis from initial studies to recent advances and provide a conceptual framework we hope will inspire and enable future work using this versatile elementary step.
在过去几十年中，烷基自由基在有机化学中的地位发生了显著变化，从难以生成且易于发生副反应的“不可控”物种，演变为能够构建无数碳 - 碳和碳 - 卤键的多功能反应中间体。自由基化学的这种成熟得益于多项进展，包括高效自由基生成方法的激增，如氢原子转移（HAT）、烯烃加成和脱羧反应。至少同样重要的是自由基官能团化方法的创新，包括自由基 - 极性交叉（RPC），使这些中间体能够参与富有成效且高效的成键步骤。然而，烷基自由基的直接参与仍然具有挑战性。在这些官能团化方法中，一种被称为自由基配体转移（RLT）的受生物启发的机理范式，已成为一种特别有前景且通用的催化形成与烷基自由基新键的方法。这种发展受到RLT催化的几个关键特征的推动，包括形成多种键（包括碳 - 卤键、碳 - 氮键和碳 - 硫键）的能力、使用简单且储量丰富的元素催化剂，以及该方法与多种自由基生成方法（包括HAT、自由基加成和脱羧反应）的内在兼容性。在此，我们概述了RLT催化从最初研究到近期进展的演变，并提供了一个概念框架，希望能激发并推动未来使用这一通用基本步骤的研究工作。
