Monodentate ligands asymmetric hydrogenation

Scheme 28.2 New classes of monodentate ligands used in asymmetric hydrogenation. R = alkyl or aryl.

Reetz and Goossen et al. reported recently the asymmetric hydrogenation of a series of enol esters using monodentate phosphite ligands 17 and 24 based on a combination of BINOL and carbohydrates or simple alcohols the results of these studies are shown in Table 28.6. 

Nevertheless, there remains a plethora of substrates that have not yet been studied using the monodentate ligand approach. In the application of asymmetric hydrogenation, it is very important to go beyond the benchmark substrates, and several studies have already shown that the scope of enantioselective hydrogenation might be much broader than was originally assumed. 

Breakthroughs that took place around the year 2000 have shown, in contrast to the common view, that indeed chiral monodentate phosphorus ligands can also lead to high enantioselectivities in a number of asymmetric hydrogenations. In the years following, monophosphines, monophos-phonites, monophosphoramidites, and monophosphites have been successfully used in the enantioselective hydrogenation of a-dehydroamino acids and itaconic acid derivatives [25],... 

Figure 4.22. Monophos as monodentate ligand in rhodium catalysed asymmetric hydrogenation...

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." ... 

THE SYNTHESIS AND APPLICATION OF BrXuPHOS A NOVEL MONODENTATE PHOSPHORUS LIGAND FOR THE ASYMMETRIC HYDROGENATION OF KETONES... 

Very recently, chiral 6-DPPon derivatives, the phospholanes 4b and 5b and the phosphepine 6b, have been prepared and studied as ligands in asymmetric hydrogenation (Figure 2.4) [14]. For comparison, the corresponding 2-alkoxypyridine systems 4a-6a were studied, too. The latter should behave as truly monodentate ligands while the pyridine systems 4b-6b should allow for complementary hydrogenbonding. 

Recent review about monodentate ligands, see (a) Jerphagnon, T., Renaud, J.-L. and Brrmeau, C. (2004) Chiral monodentate phosphorus ligands for rhodium-catalyzed asymmetric hydrogenation. Tetrahedron Asymmetry, 15, 2101-2111, and references cited therein, (b) de Vries, J.G. (2005)... 

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%... 

Highly Enantioselective or Not - Chiral Monodentate Monophosphorus Ligands in the Asymmetric Hydrogenation... 

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... 

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