Leifert Dirk, Studer Armido
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstrasse 40, 48149 Münster, Germany.
Chem Rev. 2023 Aug 23;123(16):10302-10380. doi: 10.1021/acs.chemrev.3c00212. Epub 2023 Aug 14.
Nitroxides, also known as nitroxyl radicals, are long-lived or stable radicals with the general structure RRN-O. The spin distribution over the nitroxide N and O atoms contributes to the thermodynamic stability of these radicals. The presence of bulky N-substituents R and R prevents nitroxide radical dimerization, ensuring their kinetic stability. Despite their reactivity toward various transient C radicals, some nitroxides can be easily stored under air at room temperature. Furthermore, nitroxides can be oxidized to oxoammonium salts (RRN═O) or reduced to anions (RRN-O), enabling them to act as valuable oxidants or reductants depending on their oxidation state. Therefore, they exhibit interesting reactivity across all three oxidation states. Due to these fascinating properties, nitroxides find extensive applications in diverse fields such as biochemistry, medicinal chemistry, materials science, and organic synthesis. This review focuses on the versatile applications of nitroxides in organic synthesis. For their use in other important fields, we will refer to several review articles. The introductory part provides a brief overview of the history of nitroxide chemistry. Subsequently, the key methods for preparing nitroxides are discussed, followed by an examination of their structural diversity and physical properties. The main portion of this review is dedicated to oxidation reactions, wherein parent nitroxides or their corresponding oxoammonium salts serve as active species. It will be demonstrated that various functional groups (such as alcohols, amines, enolates, and alkanes among others) can be efficiently oxidized. These oxidations can be carried out using nitroxides as catalysts in combination with various stoichiometric terminal oxidants. By reducing nitroxides to their corresponding anions, they become effective reducing reagents with intriguing applications in organic synthesis. Nitroxides possess the ability to selectively react with transient radicals, making them useful for terminating radical cascade reactions by forming alkoxyamines. Depending on their structure, alkoxyamines exhibit weak C-O bonds, allowing for the thermal generation of C radicals through reversible C-O bond cleavage. Such thermally generated C radicals can participate in various radical transformations, as discussed toward the end of this review. Furthermore, the application of this strategy in natural product synthesis will be presented.
氮氧化物，也被称为硝酰基自由基，是具有通式RRN - O的长寿命或稳定自由基。硝酰基氮原子和氧原子上的自旋分布有助于这些自由基的热力学稳定性。庞大的N - 取代基R和R的存在可防止硝酰基自由基二聚化，确保其动力学稳定性。尽管它们对各种瞬态碳自由基具有反应性，但一些氮氧化物在室温下可在空气中轻松储存。此外，氮氧化物可被氧化为氧鎓盐（RRN═O）或还原为阴离子（RRN - O），这使它们能够根据其氧化态充当有价值的氧化剂或还原剂。因此，它们在所有三种氧化态下都表现出有趣的反应性。由于这些迷人的性质，氮氧化物在生物化学、药物化学、材料科学和有机合成等不同领域有广泛应用。本综述重点关注氮氧化物在有机合成中的多种应用。关于它们在其他重要领域的用途，我们将参考几篇综述文章。引言部分简要概述了氮氧化物化学的历史。随后，讨论了制备氮氧化物的关键方法，接着考察了它们的结构多样性和物理性质。本综述的主要部分致力于氧化反应，其中母体氮氧化物或其相应的氧鎓盐作为活性物种。将证明各种官能团（如醇、胺、烯醇盐和烷烃等）可被有效氧化。这些氧化反应可使用氮氧化物作为催化剂并与各种化学计量的终端氧化剂结合进行。通过将氮氧化物还原为其相应的阴离子，它们成为有效的还原试剂，在有机合成中有有趣的应用。氮氧化物具有与瞬态自由基选择性反应的能力，这使其可用于通过形成烷氧基胺来终止自由基级联反应。根据其结构，烷氧基胺表现出较弱的C - O键，允许通过可逆的C - O键断裂热生成碳自由基。这种热生成的碳自由基可参与各种自由基转化，如在本综述结尾所讨论的。此外，还将介绍该策略在天然产物合成中的应用。
