Enamides, asymmetric catalytic

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. 

L-dopa, used in the treatment of Parkinson s disease, is best prepared by asymmetric catalytic hydrogenation (15) of the enamide [6]. The hydrogenation, performed with a soluble rhodium catalyst modified with the... 

The efficiency of an asymmetric catalytic reaction is characterized either by excess of the predominantly formed enantiomer [61], for example of the R-configuration and its optical yield (%), P = ([./ ]-[ S])/([/ ]+[ S]), or by the value of the enantioselectivity, E = [/ ]/[5], Thus, among the amino acids (prochiral enamides) with higher optically active products, the yield (for example, 2-aceta-midoacrylic acid) reaches 67%. The same is true of the asymmetric hydrogenation of prochiral ketones. 

In addition, as discussed above, oxidation reactions and reactions which use CO2 as a reagent as well as a solvent are worth investigating. Examples of both are discussed below. Finally, electrophilic processes may be advantageously transferred to supercritical CO2, as demonstrated by the improved isomerization of C4-C12 paraffins catalyzed by aluminum bromide. 2,44) Below, we describe three catalytic reactions which appear promising by these criteria asymmetric catalytic hydrogenation of enamides, ruthenium-catalyzed two-phase oxidation of cyclohexene, and the catalytic copolymerization of CO2 with epoxides. 

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. 

Asymmetry in metal-alkene coordination plays a critical role in asymmetric catalysis, with implications far beyond the scope of the present treatment. An instructive example is provided by catalytic asymmetric hydrogenation of enamides,... 

Enantioselective catalytic hydrogenation. The ruthenium(II) complexes of (R)- and (S)-l, bearing a chiral BINAP ligand, catalyze asymmetric hydrogenation of N-acyl-l-alkylidenetetrahydroisoquinolines to give (1R)- or (lS)-tetrahydroiso-quinolines in 95-100% ee.1 Thus the (Z)-enamide (2), prepared by acylation of 3,4-dihydropapaverine, is hydrogenated in the presence of (R)-l to (1R)-tetrahydroisoquinolines (3). The enantiomeric (lS)-3 is obtained on use of (S)-l as catalyst. 

Brown and coworkers [128] have studied the exchange process for the enamide complex 103, using magnetization transfer techniques (Figure 1.28). Compound 103 represents the catalytic resting state in the asymmetric homogeneous hydroge-... 

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]. 

Although the Rh-catalyzed asymmetric hydrogenations of prochiral enamides have been extensively studied and excellent results have been frequently achieved, the catalytic asymmetric hydrogenations of 2-arylacrylic acids have been less successful. Until recently most catalyst systems gave only moderate optical yields for the 2-arylpropionic acid products (77). An important breakthrough in the study of these reactions was reported by Noyori et al. By using Ru(BINAP)(OAc)2 as a catalyst precursor, these researchers obtained excellent optical yields in the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid (72). 

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