Recent developments in catalytic asymmetric hydrogenation employing P-chirogenic diphosphine ligands

Rhodium- and ruthenium-catalyzed asymmetric hydrogenations reactions employing C-2-symmetric chiral diphosphine ligands have a long history, and exceedingly high enantioselectivities have been reported. On the other hand, metal complexes containing P-chirogenic, electron-rich diphosphine ligands such as 1,2-bis(alkylmethylphosphino)ethane (BisP*) and bis(alkylmethylphosphino)methane (MiniPHOS) have been tested only recently, and proved greatly successful. These results prompted intensive research amongst organic chemists, and the scope and limitations of the use of ligands bearing the chiral center at phosphorus atoms is presented in this review. The most recent data have been collected and summarized. In terms of ligand design, it is necessary to address an important question: "which properties are responsible for very high enantioselectivity in hydrogenation reactions?". To this extent, a full discussion of new aspects on the mechanism, in particular the demonstration of a dihydride mechanism for enantioselective hydrogenation as opposed to the unsaturated mechanism widely accepted so far, also constitutes an important part of this review. 1 Introduction 2 Asymmetric Hydrogenation: Historical Overview 3 Some Outstanding Chiral Ligands 3.1 BPE and DuPHOS: Phosphine Ligands with Pseudo-Chirality at Phosphorus 3.2 BisP* and MiniPHOS: Synthesis and Characteristic Features 4 Metal-Catalyzed Enantioselective Hydrogenation Reactions 4.1 Rh-Catalyzed Asymmetric Hydrogenations 4.2 Ru-Catalyzed Asymmetric Hydrogenation of Keto Esters using BisP* 5 Mechanism of Enantioselective Hydrogenation Catalyzed by Chiral Rh Complexes: General Considerations 6 Origin of High Enantioselectivity 6.1 Empirical Rules 6.2 Mechanistic Studies with BisP* 6.3 Reaction of Rh-MiniPHOS with H-2 7 Conclusion.