Asymmetric. Hydrogenation of Enamine

Chiral monophosphite ligands were attached to PEG and used as ligands for the Rh-catalyzed asymmetric hydrogenation of C=C double bonds [125]. The polymeric catalysts 190 and 191 performed well in the asymmetric hydrogenation of 

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Kubryk, M. and Hansen, K.B. Apphcation of the Asymmetric Hydrogenation of Enamines to the Preparation of a Amino Acid Pharmacophore. Tetrahedron Asymmetry 2006,17, 205-209. 

Prior to the beginning of our work on sitagliptin, there had been some reports in the literature of catalytic asymmetric hydrogenation of enamines to access chiral secondary amines [19]. The synthesis of P-amino acids had also been established by catalytic asymmetric hydrogenation of enamides [20]. All these reports relied on N-acylenamines as substrates, since it was believed that the N-acyl group was required in order to achieve good reactivity and selectivity [21]. 

Pfaltz systems represent promising beginnings for the asymmetric hydrogenation of enamines by discrete, cationic iridium catalysts, but both require more development before they can find wide use in amine synthesis. In particular, these systems are still highly substrate dependent, meaning that a new catalyst screening is necessary for each new substrate. 

The diversity requirement of chiral amines in the synthesis of natural products and chiral drugs is everlasting and the most studies about the catalytic asymmetric hydrogenation of enamines have dealt with simple substrates to date. Hence, it is necessary to explore highly efficient enantioselective protocol to provide more complex and also industrially useful chiral amines. We are confident that the easily accessible and changeable monodentate phosphorus hgands will find a wide appli cation in this field. 

Tire polymerized or linked monodentate phosphoramidites are no longer monodentate phosphorus hgands, but why were they also discussed in this chapter as monodentate phosphorus hgands in the asymmetric hydrogenation of enamines ... 

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