Rh-catalyzed hydrogenation of enamides

Uemura developed a water-soluble phosphine-phosphinite ligand (derived from a,a-trehalose) (166) for the Rh-catalyzed hydrogenation of enamide derivatives this induced only moderate enantioselectivity [129]. 

Finally, a broad screening of ligands and ionic liquids was carried out by Feng et al. for the Rh-catalyzed hydrogenation of enamides [113]. Rhodium-ferrocenyl-diphosphine complexes with taniaphos, josiphos, walphos and mandyphos... 

The compatibility of some ILs with water has allowed the development of a highly efficient multi-phase system for the Rh-catalyzed hydrogenation of enamides (turnover numbers of >10,000). In many cases, such IL/water combinations are superior to conventional organic solvents and biphasic ILs/organic co-solvents media with respect to catalytic performance as well as to catalyst separation and recycling. The best results were obtained with Rh-ferrocenyl-diphosphine catalysts (>99% ee) in [G8GiIm]BF4/water. ... 

The BINAP-Rh -catalyzed hydrogenation of enamide 2-acetylamino-3-phenylacrylic acid was studied using the hybrid IMOMM QM/MM method [58]. It was found that the relative energy differences between diastereomers (14-PRO-/ and 14-PRO-5) in both the oxidative addition and migratory insertion steps are consistent with the experimentally observed enantioselectivity. This theoretical evidence shows a shift for this particular ligand-substrate combination as well as the hydrogenation of a-acylaminoacrylates by [Rh((S,S)-dipamp)] to a lock-and-key motif (Scheme 6). 

Fig. 3 Different approaches of H2 (pathways A-D) to the substrate-catalyst complex in the Rh-catalyzed hydrogenation of enamides and mechanism for the insertion of Ca and Cp into the Rh-H bond...

The results clearly show that these novel ligands are able to form a suitable asymmetric enviromnent around the metal resulting in high asymmetric induction. Their catalytic potential has been demonstrated in the highly enantioselective Rh-catalyzed hydrogenation of itaconates and a-enamides and Ru-catalyzed hydrogenation of p-functionalized ketone. 

Rh-catalyzed hydrogenation of simple enamides has attracted much attention recently. With the development of increasingly efficient chiral phosphorus ligands, extremely high ee-values can be obtained in the Rh-catalyzed hydrogenation of a-aryl enamides. E/Z-isomeric mixtures of -substituted enamides can also be hydrogenated, with excellent ee-values. Some efficient examples (>95% ee) of hydrogenation of a-phenylenamide and E/Z-isomeric mixtures of / -methyl-a-phenylenamide are listed in Table 26.3. 

Wink reported the use of bisphosphite ligands in the asymmetric hydrogenation of enamides (2-10% ee) [114]. In 1998, Selke synthesized a series of analogues based on 98a. Of these compounds, 147 (Fig. 27.14) was selected as ligand for the Rh-catalyzed hydrogenation of methyl (Z)-2-ace tamidocinnamate, though it induced only low enantioselectivity (13% ee) [115]. 

The BINAP-Rh catalyzed hydrogenation of functionalized olefins has a mechanistic drawback as described in Section 1.2.1. This problem was solved by the exploitation of BINAP-Ru(ll) complexes.Ru(OCOCH3)2(binap) catalyzes highly enantioselective hydrogenation of a variety of olefinic substrates such as enamides, a, (3- and (3,y-unsaturated carboxylic acids, and allylic and homoallylic alcohols (Figure 1.9). " " Chiral citronellol is produced in 300 ton quantity in year by this reaction. ... 

In contrast to the high enantioselectivities obtained for the Z substrates, hydrogenation of the E isomers usually proceeds very slowly and in a poor optical yield partly due to the E/Z double-bond isomerization. The enantioselectivity in the BINAP-Rh-catalyzed hydrogenation of E enamides is enhanced in an aprotic solvent THF to minimize the isomerization [15,56],... 

Rh-Catalyzed Hydrogenation of C=C (Lonza). 2-Piperazinecarboxylic acid derivatives are interesting intermediates, for example, for Crixivan, the well-known HIV protease inhibitor of Merck. The hydrogenation of an vmusually substituted cyclic enamide was used to produce more than 200 kg of the depicted piperazine intermediate (27d,56a). 

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