Development of Various Cross-coupling Reactions in New Media for the Electron-Transfer Reactions

本研究的目的是开发用于电子转移反应的新介质，并将这些介质用于各种有机卤化物与芳基卤化物的交叉偶联反应或选择性碳-碳形成反应。为了实现高效的交叉偶联反应，本研究采用了两种电子转移反应介质。一种是使用高活性锌，这种锌很容易通过电解制备。另一种是电化学反应体系，使用的是反应性金属阳极，如镁或锌。我们发现，在含有支持电解液的DMF溶液中，以萘为阴极，以铂为阴极，以锌为阳极，电解得到高活性锌(EGZn/naph)。在Pd(II)催化下，EGZn/naph成功地将有机溴化物有效地转化为相应的有机溴化锌，再与芳基碘溴化物反应，得到高产率的交叉偶联产物。这种方法也被应用于有效地合成非甾体抗炎药的前体，如布洛芬或萘普生。另一方面，我们发现，当以菲为介体，铂为阴极，镁或锌为阳极时，芳基卤化物发生单电子转移，优先生成芳基自由基。由此产生的芳基自由基经5-外环合成分子内C-C双键。对Bu_3SnH-AlBN生成的芳基自由基也进行了类似的环化反应，得到了有用的生物碱。最后，我们发现二氧化碳与三酸乙烯酯或丙烯基卤化物与醛的偶联反应可以高效和选择性地进行，得到相应的羧酸或高烯丙烯基醇，这是传统合成方法难以获得的，产率很高。

The purpose of this study is to develop new media for the electron-transfer reactions and to use these media in cross-coupling reactions of various organic halides with aryl halides or in selective carbon-carbon forming reactions. In order to achieve efficient cross-coupling reactions, two media for the electron-transfer reactions were employed in this study. One is to use highly reactive zinc which can readily be prepared by electrolysis. Another medium is the electrochemical reaction system using a reactive-metal anode such as magnesium or zinc.We found that the electrolysis of a DMF solution containing supporting electrolyte in the presence of naphthalene with a platinum cathode and a zinc anode gave the highly reactive zinc (EGZn/Naph). The EGZn/Naph was successfully used for efficient transformation of organic bromides to the corresponding organozinc bromides, which were reacted with aryl iodides bromides in the presence of Pd(II) catalyst to give the corresponding cross-coupled products high yields. This methodology was also applied to an efficient synthesis of the precursors of non-steroidal anti-inflammatory agents such as ibuprofen or naproxen. On the other hand, we found that a one-electron transfer to aryl halides occurred to give preferentially aryl radicals when the electrolysis of aryl halides was carried out with a platinum cathode and a magnesium or zinc anode using phenanthrene as a mediator. Aryl radicals thus generated underwent 5-exo cyclizations to intramolecular C-C double bond. Similar cyclization of aryl radicals generated by Bu_3SnH-AlBN to give useful alkaloids was also carried out. Finally, we found that coupling reactions of carbon dioxide with vinyl trifiates or those of propargylic halides with aldehydes took place efficiently and selectively to give the corresponding carboxylic acids or homoallenyl alcohols, not readily available by conventional synthetic methods, in good yields.