Ruthenium catalysts asymmetric reductive amination

Recently, Ru-JOSIPHOS complexes were found extraordinary effective for the enantioselective transfer hydrogenation of aryl ketones (168). A novel bidentate diphosphine with axial chirality (DM-SEGPHOS) was reported to form active catalyst with ruthenium for asymmetric reductive amination (169). 

Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

In this chapter, I outline our recent progress in asymmetric reductive and oxidative transformations with bifunctional molecular catalysts based on ruthenium, rhodium, and iridium complexes bearing chiral chelating amine ligands. 

As an alternative to palladium and ruthenium catalysts as racemization agents, De Vos and coworkers reported the use of Raney nickel for the DKR of aliphatic amines in toluene and a low pressure of hydrogen (0.01-0.02 MPa) at 70 °C. Its combination with CAL-B and EtOAcMeOAc led to the desired (R)-methoxyacetamides in 64—98% conversion and 80-98% ee [245], The production of optically active amines has been also possible using ketoximes instead of racemic amines as starting materials, and using metal catalysis for the racemization step. Thus, Kim and coworkers reported the asymmetric reductive acylation a system including the use of palladium on charcoal for the reduction/racemization sequence in combination with CAL-B, 2 equivalents of EtOAc, three equivalents of diisopropylethylamine, and 1 Hjatm in toluene at... 

An excellent review describing asymmetric transfer hydrogenation has been published156. Many excellent results have been achieved in recent studies of acrylic acid reductions employing the same catalysts of ruthenium or rhodium with a chiral diphosphine as were used in the hydrogen gas process1331157. In this case, however, the most common hydrogen source is the combination of formic acid with an amine. The choice of amine is often critical in the reduction shown in Scheme 30, the use... 

---