Department of Pharmaceutical, Chemical and Environmental Sciences, School of Science , University of Greenwich , Chatham Maritime, Chatham, Kent ME4 4TB , U.K.
Acc Chem Res. 2020 Jan 21;53(1):121-134. doi: 10.1021/acs.accounts.9b00586. Epub 2020 Jan 2.
Electrosynthetic organic chemistry is an old discipline that takes its root in Faraday's seminal works. The field has a rich history and is in the midst of a renaissance, due to the growing impetus of the chemical community to develop greener, more economical, and more efficient synthetic methodologies. Indeed, electrosynthesis relies on one of the greenest and cheapest reagents in the world: the electron itself. In this Account, the recent developments in the use of carboxylic acid derivatives in electrosynthesis are summarized. Until lately, the fate of the monoelectronic reduction of aromatic esters in nonprotic solvents remained unclear. Recent investigations have shown that aromatic esters are reduced and form surprisingly long-lived radical anions. Under the right conditions, these radical anions decompose into the corresponding carboxylates and alkyl radicals. These principles have been used to develop a novel electrochemical alcohol deoxygenation reaction using aromatic esters as stable and versatile radical precursors. In contrast to esters, the electrochemistry of carboxylic acids has been intensively studied. Pioneering works by Faraday and Kolbe in the late 1800s have revealed that the anodic oxidation of carboxylic acids leads to a radical decarboxylation. Interestingly, radical recombination is observed due to the very high concentration of radicals in the vicinity of the electrode. Such radical recombination is rarely observed during classical homogeneous radical reactions. The "Kolbe" reaction and its carbocationic variation have been intensively used across the fields due to their versatility. As we will develop in this Account, almost two hundred years after its discovery, the anodic decarboxylation of carboxylic acids is still relevant to modern organic chemists. For instance, we will examine how the non-decarboxylate Kolbe reaction of aromatic acids forms aroyloxy radicals and how oxycarbonyl radicals could be generated from hemioxalates. Finally, the carbocationic variant of the Kolbe reaction, known as the Hofer-Moest reaction, will be examined in the context of two newly developed reactions: a green MOM-type ether formation and the use of malonic acid derivatives as carbonyl synthons. Electrosynthesis is a powerful synthetic tool. Even if it might still be underutilized at the moment, there is little doubt that it will become one of the "classic" methods to activate small organic molecules in a very near future.
电合成有机化学是一门古老的学科，其根源可以追溯到法拉第的开创性工作。由于化学界越来越热衷于开发更绿色、更经济、更高效的合成方法，该领域拥有丰富的历史，目前正处于复兴之中。实际上，电合成依赖于世界上最绿色、最便宜的试剂之一：电子本身。在本综述中，总结了羧酸衍生物在电合成中的最新发展。直到最近，芳香酯在质子惰性溶剂中单电子还原的命运仍不清楚。最近的研究表明，芳香酯被还原并形成了出人意料地长寿命的自由基阴离子。在适当的条件下，这些自由基阴离子分解为相应的羧酸盐和烷基自由基。这些原理已被用于开发一种新型的电化学醇脱氧反应，使用芳香酯作为稳定且多功能的自由基前体。与酯相反，羧酸的电化学已得到深入研究。法拉第和科尔比在 19 世纪后期的开创性工作表明，羧酸的阳极氧化导致自由基脱羧。有趣的是，由于电极附近自由基的浓度非常高，观察到自由基的重组。这种自由基重组在经典的均相自由基反应中很少观察到。由于其多功能性，“科尔比”反应及其碳阳离子变体已在各个领域得到广泛应用。正如我们将在本综述中发展的那样，在发现后的将近两百年，羧酸的阳极脱羧反应仍然与现代有机化学家相关。例如，我们将研究芳香酸的非脱羧科尔比反应如何形成芳氧基自由基，以及如何从羟醛酸盐生成氧羰基自由基。最后，科尔比反应的碳阳离子变体，即霍弗-莫斯特反应，将在两个新开发的反应的背景下进行检查：一种绿色的 MOM 型醚形成和使用丙二酸衍生物作为羰基合成子。电合成是一种强大的合成工具。即使目前它可能还未得到充分利用，但毫无疑问，在不久的将来，它将成为激活小分子的“经典”方法之一。
