Hydrogenation chiral monophosphine

The application of a mixture of a chiral and an achiral monophosphorus ligand for the rhodium catalyzed asymmetric hydrogenation of enamides was tested by Beller and coworkers [45]. By using a mixture of a chiral monophosphine 36a and an achiral ligand tris(4 methoxyphenyl)phosphine [P(4 MeOCf,H4)3] (1 1), the N (1 phenylvi nyl)acetamide (7a) was hydrogenated to amine 8a with 88% ee, but this enantios electivity is inferior to that obtained with single monophosphine 36a (93% ee). 

Some chiral monophosphines were also prepared during the period 1971-1973. Camp (cyclohexyl o-anisyl methyl phosphine) led to a quite high ee (up to 90%) in asymmetric hydrogenation of W-acetyl dehydrophenylalanine [29] and neomenthyl diphenyl phosphine gave modest ee s in the reduction of various conjugated acids [30]. 

Early work in asymmetric hydrogenation by Knowles [30] and Horner [31] was accompanied hand in hand by important breakthroughs by Kagan [32] and Knowles [33]. Two ligands feature prominently in this regard the tartrate-derived bidentate ligand DIOP (5, Equation 1) [32] and the chiral monophosphine CAMP (8, Equation 2), which can be prepared by resolution with menthol [33]. 

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],... 

The enantioselectivity is not very sensitive to the nature of the allylic alcohol. By contrast, titanium and tartrates are essential to the success. This catalyst components combination is unique note the difference with the L-Dopa asymmetric hydrogenation, which can be carried out with hundreds of C2-chiral diphosphines, even monophosphines, but with a limited number of substrates only. 

Furthermore, secondary monophosphine ligand, (2S,5S) 2,5 diphenylphospho lane, was also used in the rhodium catalyzed asymmetric hydrogenation of P substituted enamide for the synthesis of chiral N acetyl amines, albeit with low enantioselectivity (<28% ee) [46]. 

Catalytic asymmetric synthesis, in particular, hydrogenations, C-C bond formations, and tautomerizations, rely to a great extent on chiral 6frphosphines (Scheme 1—43) rather than on monophosphines as catalyst ligands. DIPAMP [l,2-ethylenebis(o-anisylphenylphosphine), 56] belongs to the rare examples where chirality resides directly at an asymmetric phosphorus atom (Scheme 1-43). More often enantiodiscrimination originates from carbon stereocenters, as present in DIOP " [2,2-dimethyl-1,3-dioxolane-... 

Achiral Monophosphine/Ru/Chiral Diamine-Catalyzed Asymmetric Hydrogenation of Ketones... 

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