Chemistry Department, University of Wisconsin, Madison, 53706, United States.
Acc Chem Res. 2012 Feb 21;45(2):164-70. doi: 10.1021/ar2000698. Epub 2011 Sep 16.
The Birch Reduction is one of the main reactions of organic chemistry. The reaction involves the reaction of dissolving metals in ammonia with aromatic compounds to produce 1,4-cyclohexadienes. Discovered by Arthur Birch in 1944, the reaction occupies 300 pages in Organic Reactions to describe its synthetic versatility. Thus, it is remarkable that the reaction mechanism has been so very controversial and only relatively recently has been firmly established. Perhaps this is not that surprising, since the reaction also has many unusual and esoteric mechanistic facets. Here, I provide a description of how I have applied ever-evolving levels of quantum mechanics and a novel experimental test to understand details of the mechanism and the origins of the selectivities observed in the Birch reduction. The reaction involves an initial radical anion resulting from introduction of an electron from the blue liquid ammonia solution of free electrons formed by the dissolution of Li or related metals. This radical anion is protonated by an alcohol and then further reduced to a carbanion. Finally, the carbanion is protonated using a second proton to afford a nonconjugated cyclohexadiene. The regiochemistry depends on substituents present. With 18 resonance structures in the case of anisole radical anion, prediction of the initial protonation site would seem difficult. Nevertheless, computational methods from Hückel theory through modern density functional calculations do correctly predict the site of protonation. An esoteric test established this mechanism experimentally. The nature of the carbanion also is of mechanistic interest, and the preponderance of the resonance structure shown was revealed from Hückel calculations involving variable bond orders. For the trianion from benzoic acid, parallel questions about structure are apparent, and have been answered. Some mechanistic questions are answered experimentally and some by modern computations. Recently, our mechanistic understanding has led to a variety of synthetic applications. For example, the preparation of alkyl aromatics from benzoic acids makes use of the intermediates formed in these reactions. This Account provides an overview of both experimental techniques and theoretical methodology used to provide detailed mechanistic understanding of the Birch Reduction.
硼氢化还原反应是有机化学中的主要反应之一。该反应涉及将溶解在氨中的溶解金属与芳香族化合物反应，生成 1,4-环己二烯。该反应由 Arthur Birch 于 1944 年发现，在《有机反应》中用 300 页的篇幅描述了其合成的多功能性。因此，令人惊讶的是，该反应的机制一直存在很大争议，直到最近才得到了确凿的证实。也许这并不奇怪，因为该反应还具有许多不寻常和深奥的机制方面。在这里，我将描述我如何应用不断发展的量子力学水平和新颖的实验测试来理解硼氢化还原反应的机制细节和观察到的选择性的起源。该反应涉及由溶解的 Li 或相关金属形成的蓝色液态氨溶液中自由电子引入电子后形成的初始自由基阴离子。该自由基阴离子被醇质子化，然后进一步还原为碳阴离子。最后，使用第二个质子将碳阴离子质子化，得到非共轭环己二烯。区域化学取决于存在的取代基。对于茴香醚自由基阴离子，有 18 个共振结构，预测初始质子化位置似乎很困难。然而，从休克尔理论到现代密度泛函计算的计算方法确实正确预测了质子化位置。一种深奥的测试从实验上证实了这一机制。碳阴离子的性质也是机制上的兴趣所在，并且通过涉及可变键序的休克尔计算揭示了共振结构的优势。对于苯甲酸的三阴离子，关于结构的平行问题是显而易见的，并且已经得到了回答。一些机制问题通过现代计算来回答，而一些则通过实验来回答。最近，我们对机制的理解导致了各种合成应用。例如，从苯甲酸制备烷基芳烃利用了这些反应中形成的中间体。本综述提供了用于提供硼氢化还原反应详细机制理解的实验技术和理论方法的概述。
