Catalytic enantioselective hydrosilylation of pyridines and benzannulated congeners

吡啶的部分还原是合成化学中一个尚未得到满意解决的问题，也是因为传统的Birch还原和最新的过渡金属催化加氢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的硼氢化和硅氢化，最近发展的几种方法甚至允许区域选择性地将吡啶本身和取代的吡啶分别转化为1，2-和1，4-二氢吡啶。然而，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1，4-选择性的硅氢加成反应，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Ru(II)络合物的Ru-S键上的Si-H键的协同活化。硅-氢键的断裂产生硫稳定的硅阳离子，它立即被吡啶氮原子隔离，得到吡啶离子。同时生成的Ru(II)氢化物络合物选择性地还原吡啶离子中间体1，4-。这种不同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位上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。这个项目的短期目标是开发手性Ru(II)催化剂，使手性4-取代吡啶离子上的对映选择性氢化物转移成为可能。同样的原则将扩展到同系喹啉(1，4-还原)和适当的异喹啉(1，2-还原)。在建立该方法之后(以及在另一个可能的供资期间)，长期目标可能是将所获得的含氮二氢芳烃应用于迄今前所未有的对映体选择性转移氢硅化反应。

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.