Catalytic enantioselective hydrosilylation of pyridines and benzannulated congeners

吡啶的部分还原是合成化学中尚未令人满意地解决的问题，这也是因为常规的Birch还原和现有技术的过渡金属催化氢化通常不能产生所需的二氢吡啶。有效的替代方法是化学选择性硼氢化和硅氢化，最近开发的几种方法甚至允许吡啶本身和取代的吡啶分别区域选择性地转化为1，2-和1，4-二氢吡啶。但这些催化剂的范围仍然相当狭窄。我们的实验室现在完成了高度选择性的1，4-硅氢加成反应，甚至允许4-取代吡啶的1，4-还原。成功的关键是作为催化剂的配位不饱和钌（II）络合物的极性Ru-S键处的Si-H键的协同活化。Si-H键的断裂产生硫稳定的硅阳离子，其立即被吡啶氮原子螯合以提供吡啶离子。同时形成的氢化钌（II）络合物然后选择性地还原吡啶鎓离子中间体1，4。这种不寻常的区域选择性现在打开了将取代的吡啶与安装在吡啶核心的4-位的额外取代基转化为相应的不对称取代的1，4-二氢吡啶的机会。该项目的短期目标是开发手性钌（II）催化剂，使对映选择性氢化物转移到前手性4-取代吡啶鎓离子上成为可能。相同的原理将扩展到同源喹啉（1，4-还原）和适当的异喹啉（1，2-还原）。建立的方法（和在另一个潜在的资金期间）的长期目标可能是应用所获得的含氮二氢芳烃在迄今为止前所未有的对映选择性转移氢化硅烷化。

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.