Metal Catalyzed 1,2-Amino-Alcohol & Diamine Synthesis

说明(申请人提供)：邻氨基醇和二胺是一类重要的化合物，很难以快速和对映选择性的方式获得。最近发现的将亚胺锆络合物插入到环氧化物中，为开发一种直接和立体控制的方法来获得这些化合物提供了希望。本研究探讨了这种新的插入反应的范围和机理，目的是开发一种新的邻氨基醇和邻二胺的催化不对称合成。该反应涉及第四族金属配合物(LXM=NR，M=Ti或Zr)在环氧化物和氮杂环丙烷的C-X键(X=O或NP)上的正式插入。由此产生的金属环的质子化有望释放出所需的邻氨基醇或二胺。当使用化学计量比的胺作为质子源时，使用催化亚胺络合物，可以在一次操作中将环氧化物或氮杂环丙烷全部转化为氨基醇或二胺。当使用适当的手性、非外消旋配体时，该序列应该能够通过中间底物的去对称化或外消旋底物的动力学拆分来实现不对称催化。根据机理研究的结果，外消旋底物的动态动力学拆分是可能的。最终，这种方法有望允许快速和立体控制地获得邻近的氨基醇和二胺。

DESCRIPTION (provided by applicant): Vicinal amino-alcohols and diamines are an important class of compounds that are difficult to access in rapid and enantioselective fashion. The recently discovered insertion of imidozirconium complexes into epoxides holds promise for the development of a direct and stereo-controlled method to access these compounds. The proposed study examines the scope and mechanism of this novel insertion reaction, with the goal of developing a new catalytic asymmetric synthesis of both vicinal amino-alcohols and vicinal diamines. The proposed reaction involves the formal insertion of group IV imidometal complexes (LxM=NR, M = Ti or Zr) across the C-X bond (X = O or NP) of epoxides and aziridines. Protonation of the resulting metallacycle is anticipated to liberate the desired vicinal amino-alcohol or diamine. The overall conversion of epoxide or aziridine to amino-alcohol or diamine should be possible in a single operation using catalytic imidometal complex when a stoichiometric amine is used as the proton source. When appropriate chiral, non-racemic ligands are employed, this sequence should be capable of asymmetric catalysis via the desymmetrization of meso substrates or the kinetic resolution of racemic substrates. Depending upon the results of the mechanistic investigations, the dynamic kinetic resolution of racemic substrates may be possible. Ultimately, this method is expected to allow rapid and stereocontrolled access to vicinal amino-alcohols and diamines.