Enamide asymmetric hydrogenations

Scheme 24. Examples of Rh-catalyzed asymmetric hydrogenation reactions of enamide derivatives...

Several S/N ligands have also been investigated for the asymmetric hydrogenation of prochiral olefins. Thus, asymmetric enamide hydrogenations have been performed in the presence of S/N ligands and rhodium or ruthenium catalysts by Lemaire et al., giving enantioselectivities of up to 70% ee. Two... 

Asymmetric hydrogenation of a cyclic enamide (Approach B) had very sparse literature precedents [7]. It should also be noted that preparation of these cyclic imines and enamides is not straightforward. The best method for the synthesis of cyclic imines involves C-acylation of the inexpensive N-vinylpyrrolidin-2-one followed by a relatively harsh treatment with refluxing 6M aqueous HC1, which accomplishes deprotection of the vinyl group, hydrolysis of the amide, and decarboxylation (Scheme 8.6) [8]. 

The asymmetric reduction of enamides using hydrogenation conditions is a well documented reaction with a number of groups reporting excellent results [14]. Syn delivery of hydrogen from the same face of the molecule ensures that the enamide geometry defines the relative stereochemistry obtained, and a range of chiral catalysts have been developed to control the absolute stereochemistry. However, a... 

It initially appeared that it should be feasible to carry out the asymmetric hydrogenation using bromo-enamide 39 and to introduce the nitrile group as the final chemical transformation (Scheme 9.29). 

With all other pieces of the synthesis in place our attention now focused on the final piece in the jigsaw-the asymmetric hydrogenation of the amide enamide 42. Screening of hydrogenation conditions rapidly led to identification of a number of conditions which allowed the desired hydrogenation to proceed at low catalyst loadings and in non-chlorinated solvents (Table 9.9). 

The asymmetric hydrogenation oftetrasubstituted enamides remains a challenging goal in synthetic organic chemistry. In particular, reduction of an acylic enamide bearingfourdistinctgroups (as in enamides 22 and 42) has yet to be demonstrated by another group at the time of writing. In this section a brief outline of currently documented reductions of tetrasubstitued enamides is presented. 

Enamides, in addition to the acrylates shown above, are also asymmetrically hydrogenated with many of the same systems that prove useful for the acetamidoacrylate reductions. The Rh(I)/BICP (2(/J)-2/(i)-bis(dipenylphosphino)-1(R),] (R)-dicyclopenlane) 132 and Rh(I)/DuPHOS systems work well (>90% ee) for the asymmetric hydrogenation of /3-acctamidovinyl methoxymethyl ethers... 

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,... 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

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