Catalytic enantioselective hydrosilylation of pyridines and benzannulated congeners

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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.