Development of Catalytic Oxidation of Organonitrogen Compounds and Its Application to Organic Syntheses.

煤和油砂中含的有机氮化合物转化为有用物质是工业有机化学领域的研究热点。因此，在本研究中，我们的目标是利用金属络合催化剂开发清洁、催化氧化有机氮化合物。值得注意的是以下结果。(1)以SeO_2为催化剂，Na_2WO_4为催化剂，30%的双氧水为催化剂，仲胺氧化成硝态氮顺利进行。四氢喹啉以优异的收率转化为具有有效抗菌活性的羟肟酸。(2)本研究发展的氧化反应为不同亲核试剂处理硝基化合物时仲胺的取代提供了新的通用策略。例如，建立了一种简单、高效、廉价的由仲胺合成氨基酸的方法。因此，用过氧化氢催化氧化仲胺，然后用氰化氢处理得到α -氰羟基胺。羟基胺水解得到n -羟基氨基酸，经催化加氢生成氨基酸。用旋光性烯醇酯处理硝基酮也可得到高非对映选择性的β -羟氨基酸酯。(3)考虑到相邻氮的C-H键直接活化，我们开发了钌催化叔胺与过氧化叔丁基氧化得到相应的-（叔丁基二氧基）烷基胺。叔甲基胺的选择性n -去甲基化是通过氧化和酸催化水解来完成的。(4)以丙酮为氢受体时，氨基醇与RuH_2(PPh_3)_4的分子内脱氢反应顺利进行。通过这种方法可以得到各种内酰胺。

Transformation of organonitrogen compounds being contained in coal and oil-sand into useful material has attracted much attention in the field of industrial organic chemistry. In this study we thus aimed at developing clean, catalytic oxidation of organonitrogen compounds with metal-complex catalysts. Noteworthy are the following results.(1) Oxidation of secondary amines into nitrones undergoes smoothly, with SeO_2 catalyst as well as Na_2WO_4 is used with 30% aqueous hydrogen peroxide. Tetrahydroquinolines are converted into hydroxamic acids of potent antibacterial activity in excellent yields.(2) The oxidation developed in this study provides new and general strategy for the substitution at the alpha-position of secondary amines upon treatment of nitrones with various nucleophiles. For instance, simple, efficient, and inexpensive method for synthesis of amino acids from secondary amines has been established. Thus, catalytic oxidation of secondary amines with hydrogen peroxide followed by treatment with hydrogen cyanide gives alpha-cyanohydroxyl amines. Hydrolysis of the hydroxyl amines affords N-hydroxyamino acids which undergo catalytic hydrogenation to give amino acids. Treatment of nitrones with optically active enolates also gives beta-hydroxyamino acid esters in high diastereoselectivity.(3) In view of direct activation of C-H bonds adjacent to nitrogen of amines we have developed ruthenium-catalyzed oxidation of tertiary amines with tert-butyl hydroperoxide to give the corresponding alpha- (tert-butyldioxy) alkylamines. Selective N-demethylation of tertiary methyl amines is performed by the oxidation followed by acid catalyzed hydrolysis.(4) Intramolecular dehydrogenation of amino alcohols with RuH_2(PPh_3)_4 has been found to proceed smoothly when acetone is used as a hydrogen acceptor. Various lactams can be thus obtained by this method.