Asymmetric hydrogenation phosphoramidites

Since monodentate phosphoramidites are so successful in asymmetric hydrogenation - both because of their performance and their ease of preparation - a logical extension is their application in recyclable systems. Doherty et al. were the first to prepare polymer-supported phosphoramidites by using the monomers 40 and 41 (Scheme 28.12) these led to high ee-values which fell somewhat upon polymerization [78]. The catalyst was shown to be capable of being recycled at least four times. 

Phosphoramidites are probably the most versatile ligands in this series as in amidites the substituents at the nitrogen atom are in close proximity to the metal centre and also the substituents could carry chiral centres. In Figure 4.22 we have depicted the simplest derivative, named Monophos , which is highly efficient for asymmetric hydrogenation but for a variety of other reactions as well. The ligand is much easier to make than most, if not all, chiral bidentate phosphine ligands and surely commercial applications will appear. 

Chiral monodentate phosphites and phosphoramidites are also effective ligands for Rh-catalyzed asymmetric hydrogenation of enamide substrates. As seen in the structure of MonoPhos illustrated in Figure 1.2, combination of the mod-ihed BINOF backbone and the amine part gives a structural variety to this type of ligand. Combinatorial methods are effective for optimization of the chiral structures.Elucidation of the hydrogenation mechanism catalyzed by the MonoPhos-Rh complex is in progress." ... 

Monodentate phosphoramidites, in particular (9) and its octahydro analogue, are found to be excellent ligands for the rhodium-catalysed asymmetric hydrogenation of aromatic enol acetates, enol carbamates, and 2-dienol carbamates with up to 98%... 

Phosphoramidites, a ligand class that has only recently been introduced into asymmetric hydrogenation, in the form of hybrid chelate ligands [29], induce excellent enantioselectivity as monodentate ligands. Thus de Vries, Feringa, and co-workers could reduce standard substrates in >96% ee with a rhodium complex based upon the binaphtholphosphoramidite 3d, once the solvent and reaction temperature had been optimized [30],... 

Considerable success has been realized for asymmetric hydrogenations of carbon-carbon unsaturation with monodentate ligands, especially those derived from BINOL. The most popular class is the phosphoramidites (157) as used by DSM.200 20 Phosphites (158) have also been successfully used in a wide range of asymmetric hydrogenations,202 as have phosphonites (159).203 204 These ligands are discussed in depth in Chapter 14. 

Whereas bidentate phosphites and phosphonites are excellent ligands for rhodium-catalyzed asymmetric hydrogenation, bidentate phosphoramidites (not shown) gave very poor results with low reaction rates and enantioselectivities. Results of a number of other monodentate phosphoramidites in the asymmetric hydrogenation of. V-acetyl dehydrophenylalanine derivatives are shown in Table 14.7.31-35-36-39-40... 

The combinatorial approach was also investigated successfully with the phosphoramidite ligands 24 in the rhodium-catalyzed asymmetric hydrogenation of 27a and 27b (Scheme 14.5).4)1... 

Recently, Reek et al. published the synthesis of a 9H,9 H- [4,4 ]bicarbazole-3,3r-diol (BICOL)-based chiral monodentate phosphoramidite ligand, which was functionalized with two different third-generation carbosilane dendritic wedges (Fig. 26) [57]. As reference reaction in the catalytic study, the rhodium-catalyzed asymmetric hydrogenation of Z-methyl-a-acetamido-cinnamate was chosen. Using a ligand-to-rhodium ratio of 2.2 led to enantio-selectivities which were comparable to the results obtained using the parent BINOL-derived monodentate phosphoramidite MonoPhos. 

Scheme 8.9 Asymmetric hydrogenation of arylenamides with dendritic phosphoramidite ligands.

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 ... 

Figure 9.12 Other phosphine phosphoramidite ligands for asymmetric hydrogenation.

Scheme 9.11 Rh catalyzed asymmetric hydrogenation of ortho substituted arylenamides with a triphosphorus bidentate phosphine phosphoramidite ligand 49.

Reek et al.73 developed a new bicarbazolediol-74 (BICOL)-based, chiral monodentate phosphoramidite ligand, in which the Ai-sites in the bicarbazole skeleton permitted the easy introduction of metal centers. As a model reaction, the Rh-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate was evaluated. Using a ligand to rhodium ratio of 2.2, the enantioselectivity induced by the rhodium complex (Figure 10.7) was 93% at full conversion,... 

Hydrogenation Easily prepared monodentate phosphoramidite ligands containing a BINOL residue are employed in conjunction with (cod)2RhBp4 in asymmetric hydrogenation of dehydroamino acid derivatives and a-substituted acrylic esters (ee > 99% reachable). 

In the search for new ligands for asymmetric catalysis Ben L. Feringa and coworkers developed the synthesis of chiral monodentate phosphoramidites (PipPhos) (Figure 3.20) which were excellent ligands for asymmetric hydrogenation of aromatic enol acetates, and enol carbamates with high ee values up to 98%. 

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