C2-对称面手性RuPHOX-Ru催化的不对称氢化反应及其在手性药物合成中的应用

相比于中心手性和轴手性的配体,具有面手性(主要是基于二茂铁)的配体受到的关注较少,基于二茂钌骨架的面手性配体更是鲜有报道。二茂铁与二茂钌的2个环戊二烯负离子环之间的距离分别是0.332 nm和0.368 nm,即二茂钌的2个环戊二烯负离子环之间的距离要比相应的二茂铁的长约10%,这使得以二茂钌为骨架的面手性配体在电子效应与立体效应方面与以二茂铁为骨架的有所差异。本课题组开发的基于二茂钌的C2-对称双膦-(口恶)唑啉配体RuPHOX在许多反应,特别是钌催化的不对称氢化反应中,显示出了优异的化学稳定性和催化性能。其与金属络合后具有双金属反应中心,在提高反应活性的同时,形成更大的空间位阻,合成的RuPHOX的钌络合物RuPHOX-Ru可直接用于含C=O或C=C键底物的不对称氢化反应中。本文简要综述了RuPHOX-Ru催化的含C=O、C=C以及同时含C=O和C=C双键等底物的不对称氢化反应,以及其在手性药物合成中的应用。

C2-Symmetric Planar Chiral RuPHOX-Ru Catalyzed Asymmetric Hydrogenations and Their Applications in Chiral Drug Synthesis

Comparing to the various chiral ligands bearing both central and axial chirality, planar chiral ligands, mainly referring to those with ferrocene backbone, have not received much attention. As the analogs of ferrocenyl ligands, chiral ruthenocenes have received much less attention. The distance between the two cyclopentadienyl rings in ferrocene and ruthenocene is 0.332 and 0.368 nm, respectively. The approximate 10% longer distance between the two rings in ruthenocene is expected to present different electronic and steric effects compared with those exhibited by ferrocene ligands. A ruthenocenyl phosphino-oxazoline ligand, RuPHOX, which has been developed by our research group, shows good chemical stability and excellent catalytic behaviors in several types of asymmetric catalysis, in particular Rucatalyzed asymmetric hydrogenation. After complexation with metal, it has bimetallic reaction center, which greatly improved the reaction activity and formed a larger steric hinerance. Subsequently, the ruthenocene-based rutheniumcomplex, RuPHOX-Ru, has been synthesized and used directly in the asymmetric hydrogenation of many types of substrates bearing either C=O or C=C bonds. This review provides a brief summary on the planar chiral RuPHOX-Ru catalyzed asymmetric hydrogenation reactions of various substrates bearing C=O or C=C bonds as well as those bearing both C=O and C=C bonds, and their applications in chiral drug synthesis.