Asymmetric reductive amination metal catalysts

Asymmetric catalytic reduction reactions represent one of the most efficient and convenient methods to prepare a wide range of enantiomerically pure compounds (i.e. a-amino acids can be prepared from a-enamides, alcohols from ketones and amines from oximes or imines). The chirality transfer can be accomplished by different types of chiral catalysts metallic catalysts are very efficient for the hydrogenation of olefins, some ketones and oximes, while nonmetallic catalysts provide a complementary method for ketone and oxime hydrogenation. 

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. 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

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... 

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