Discovery of a carbon radical producing catalyst and its application to organic synthesis
Discovery of a carbon radical producing catalyst and its application to organic synthesis
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发表时间：
2003
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通讯作者：
Y. Ishii;S. Sakaguchi
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作者：
Y. Ishii;S. Sakaguchi
碳自由基，典型地以烷基自由基为例，是高度反应性的化学物质。近年来，各种产生碳自由基的方法得到了积极的研究，并在有机合成中得到了广泛的应用。产生烷基自由基的典型方法是在自由基引发剂如AIBN的存在下使烷基卤化物与Bu 3SnH或（Me 3Si）3SiH反应，巴顿酯或酰基过氧化物的热分解，或金属离子的单电子氧化。1）然而，所有这些方法都是化学计量反应，适合于小规模实验室使用，但难以应用于大规模合成。存在用于产生烷基自由基的工业方法，例如在自由基引发剂存在下或在光照射下烷烃的反应。这些方法用于烷烃的自氧化。然而，这种自氧化过程需要在高温下进行的苛刻反应条件。在这样的温度条件下，发生烷烃的C-H键均裂，以及具有比C-H键低的键能的C-C键均裂。因此，反应选择性低，反应效率低。2）迄今为止，还没有一种在温和条件下均裂烷烃碳氢键，选择性地产生碳自由基的通用方法。为了实现这一点，需要一种在温和条件下产生碳自由基的新方法。这种方法将成为有机合成不可缺少的工具。近年来，我们发现邻苯二甲酰亚胺（NHPI）生成的邻苯二甲酰亚胺N-氧基（PINO）自由基在温和条件下从烷烃、醇、醚、缩醛和醛等烃类的碳氢键上夺取一个氢原子，并以高选择性和高催化效率生成相应的碳自由基。3）NHPI被命名为“碳自由基生成催化剂”（以下简称CRPC）。使用CRPC使得能够从烷烃生产含氧化合物，例如酮和羧酸。该CRPC还促进了官能团向烷烃的加成，在温和条件下以高选择性产生硝基烷烃、烷基磺酸和烷氧基化物，这两者在以前都难以实现。通过用分子氧一步氧化环己烷以高产率生产二羧酸如己二酸（通常通过硝酸氧化制备）也已成为可能。一氧化二氮（N2 O）是具有比二氧化碳高300倍或更高的全球变暖效应的化合物，其不可避免地由硝酸氧化法产生。从绿色化学的观点来看，寻找一种不产生作为副产物的N2 O的制造己二酸的方法是非常重要的。使用CRPC的反应是从烷烃生成烷基自由基的创新方法，将对化学工业产生重大影响。一些使用CRPC方法的反应已经工业化。
Carbon radicals, typically exemplified by alkyl radicals, are highly reactive chemical species. Various methods for generating carbon radicals have been actively studied in recent years with wide applications to organic synthesis. Typical methods for the generation of alkyl radicals are by the reaction of alkyl halides with Bu3SnH or (Me3Si)3SiH in the presence of radical initiators such as AIBN, the thermal decomposition of Barton esters or acyl peroxide, or one-electron oxidations by metal ions.1) However, all of these methods are stoichiometric reactions, which are suitable for small-scale laboratory use but difficult to apply to large-scale synthesis. There are industrial methods for the generation of alkyl radicals, such as the reaction of alkanes in the presence of a radical initiator or under photoirradiation. These methods are used for the autoxidation of alkanes. However, this auto-oxidation procedure requires harsh reaction conditions, carried out under high temperature. Under such temperature conditions, the C-H bond homolysis of alkanes occurs, as well as C-C bond homolysis, which has a lower bond energy than C-H bonds. Therefore, reaction selectivity is low and reaction efficiency is insufficient.2) Until now, there has been no satisfactory general method for homolytic cleavage of the carbon-hydrogen bond of alkanes under mild conditions to selectively produce carbon radicals. In order to accomplish this, a new method for the generation of carbon radicals under mild conditions is required. Such a method will become an indispensable tool for organic synthesis. Recently, we found that phthalimide N-oxyl (PINO) radical, generated from N-hydroxyphthalimide (NHPI), abstracts a hydrogen atom from the carbon-hydrogen bond of various hydrocarbons including alkanes, alcohols, ethers, acetals, and aldehydes under mild conditions, and forms the corresponding carbon radical with high selectivity and high catalytic efficiency.3) NHPI has been named a “Carbon Radical Producing Catalyst” (hereafter CRPC). Using a CRPC has enabled production of oxygen-containing compounds, such as ketones and carboxylic acids, from alkanes. This CRPC has also facilitated the addition of functional groups to alkanes, resulting in nitroalkanes, alkyl sulfonic acids, and oxyalkylates under mild conditions with high selectivity, both of which were difficult to accomplish previously. It has also become possible to produce dicarboxylic acids such as adipic acid, usually manufactured through nitric acid oxidation, by one-step oxidation of cyclohexane by molecular oxygen in good yield. Nitrous oxide (N2O) is a compound having a global warming effect 300 times or higher than carbon dioxide, which is inevitably produced by the nitric acid oxidation method. Finding a method for manufacturing adipic acid without producing N2O as a by-product is very important from the viewpoint of green chemistry. Reactions using CRPC are innovative methods for generating alkyl radicals from alkanes and will have a significant impact on the chemical industry. Some reactions using the CRPC method have already been industrialized.