Enamides transfer hydrogenation

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. 

At this point mechanistic studies have reached an impasse. All of the observable intermediates have been characterized in solution, and enamide complexes derived from diphos and chiraphos have been defined by X-ray structure analysis. Based on limited NMR and X-ray evidence it appears that the preferred configuration of an enamide complex has the olefin face bonded to rhodium that is opposite to the one to which hydrogen is transferred. There are now four crystal structures of chiral biphosphine rhodium diolefin complexes, and consideration of these leads to a prediction of the direction of hydrogenation. The crux of the argument is that nonbonded interactions between pairs of prochiral phenyl rings and the substrate determine the optical yield and that X-ray structures reveal a systematic relationship between P-phenyl orientation and product configuration. 

Each isomer of enamide complex possesses two diastereotopic faces which give distinct products on hydrogen addition. Only one direction of addition is productive since the Rh-H bond should be 5yn-coplanar with the olefin C=C for maximum overlap in the transfer stage. This means that stereoselectivity is controlled by the relative free-energies of addition along... 

Supercritical carbon dioxide represents an inexpensive, environmentally benign alternative to conventional solvents for chemical synthesis. In this chapter, we delineate the range of reactions for which supercritical CO2 represents a potentially viable replacement solvent based on solubility considerations and describe the reactors and associated equipment used to explore catalytic and other synthetic reactions in this medium. Three examples of homogeneous catalytic reactions in supercritical CC are presented the copolymerization of CO2 with epoxides, ruthenium>mediated phase transfer oxidation of olefins in a supercritical COa/aqueous system, and the catalyic asymmetric hydrogenation of enamides. The first two classes of reactions proceed in supercritical CO2, but no improvement in reactivity over conventional solvents was observed. Hythogenation reactions, however, exhibit enantioselectivities superior to conventional solvents for several substrates. 

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. 

Figure 4.2 represents the simplest construction consistent with this information, and is the mechanism most widely accepted for Rh asymmetric hydrogenation. It still needs to be treated with some caution because of the dynamic nature of the ground state, and the possibility for direct interconversion of enamide diastereomers without dissociation. For example, the kinetics and spectroscopic observations cannot rule out an alternative in which hydrogen added to a part-dissociated enamide complex, which reverted to the preferred intermediate by rapid olefin dissociation-recombination prior to internal hydride transfer. If hydrogen adds reversibly to the solvate complex (which is present at low concentration) to produce a transient / -intermediate without interconversion of ortho- and para-Hj, then this must react irreversibly with substrate in the rate-determining step to accord with the observed kinetics. These alternative possibilities can only be discriminated by further experiment. 

An interesting mechanistic study (Scheme 31.26), supported by control experiments and density functional theory (DFT) calculation, shows a crucial function of the chiral ligand and proposes the following pathway. The authors showed the determinant role of the hydrogen atom of the enamide moiety. Based on deuterium labeling and supported by DFT calculation, a (3-hydride elimination of the enamide proton followed by a hydride transfer from the... 

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