Catalytic enantioselective hydrosilylation of pyridines and benzannulated congeners

吡啶和苯环化同系物的催化对映选择性氢化硅烷化

基本信息

批准号：
250883966
负责人：
Professor Dr. Martin Oestreich
金额：
--
依托单位：
Institut für Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/250883966?language=en
关键词：
Catalytic enantioselective hydrosilylation pyridines benzannulated

项目摘要

The partial reduction of pyridines is a problem in synthetic chemistry not yet solved satisfactorily, also because conventional Birch reduction and state-of-the-art transition metal-catalyzed hydrogenation generally do not produce the desired dihydropyridine. Effective alternatives are chemoselective hydroboration and hydrosilylation, and several recently developed methods even allow for the regioselective transformation of pyridine itself and substituted pyridines into 1,2- and 1,4-dihydro-pyridines, respectively. The scope of these catalyses remained rather narrow though. Our laboratory now accomplished a highly 1,4-selective hydrosilylation that even allows for the 1,4-reduction of 4-substituted pyridines. Key to success was the cooperative activation of Si-H bonds at the polar Ru-S bond of a coordinatively unsaturated ruthenium(II) complex as catalyst. The cleavage of the Si-H bond yields a sulfur-stabilized silicon cation that is immediately sequestered by the pyridine nitrogen atom to afford a pyridinium ion. The ruthenium(II) hydride complex formed at the same time then reduces the pyridinium ion intermediate 1,4-selectively. This unusual regioselectivity now opens the opportunity to transform substituted pyridines with an additional substituent installed at the 4-position of the pyridine core into the corresponding asymmetrically substituted 1,4-dihydropyridines. The short-term objective of this project is the development of chiral ruthenium(II) catalysts that make an enantioselective hydride transfer onto prochiral 4-substituted pyridinium ions possible. The same principle will be extended to cognate quinolines (1,4-reduction) and appropriate isoquinolines (1,2-reduction). The long-term objective after establishment of the methodology (and during another potential funding period) could be the application of the obtained nitrogen-containing dihydroarenes in hitherto unprecedented enantioselective transfer hydrosilylations.

吡啶的部分还原是尚未令人满意求解的合成化学问题的问题，这也是因为常规的桦木还原和最先进的过渡金属催化的氢化通常不会产生所需的二氢吡啶。有效的替代方案是化学选择性水合和氢硅烷化，最近开发的方法甚至可以使吡啶本身的区域选择性转化，并分别将吡啶取代为1,2-和1,4-二氢吡啶。这些催化剂的范围仍然很狭窄。我们的实验室现在完成了高度1,4选择性的氢硅烷化，甚至可以减少4个取代的吡啶。成功的关键是Si-H键在协调不饱和芳族（II）复合物作为催化剂的极性RU-S键上的合作激活。 Si-H键的裂解产生了硫稳定的硅阳离子，该硅阳离子立即被吡啶氮原子隔离，以提供吡啶丁离子。同时形成的氢化物（II）氢化物络合物，然后降低吡啶基离子中间体1,4位。现在，这种不寻常的区域选择性为在吡啶核的4位安装的附加取代基转化为相应的不对称取代的1,4-二氢吡啶的额外取代基提供了转化取代的吡啶的机会。该项目的短期目标是开发手性钌（II）催化剂，这些催化剂使映射氢化物转移到可能的4次取代的吡啶基离子上。相同的原理将扩展到同源喹啉（减少1,4）和适当的等喹啉（1,2降低）。建立该方法（以及在另一个潜在的资金期间）后的长期目标可能是将获得的含氮二氢储罗在迄今为止前所未有的对映选择性转移水平易易容性中应用。