Asymmetric hydrogenation compounds

Scheme 25. Rh-catalyzed asymmetric hydrogenation reactions leading to a biologically active compound...

Scheme 9 Asymmetric hydrogen-mediated coupling of conjugated alkynes to carbonyl compounds and imines...

The BINAP system of general structure 111 can be used in asymmetric hydrogenations the compound in which Ar = S.S-MejCgHj, R1 = R2 = 4-MeOCgH4,... 

Asymmetric hydrogenation of nitrones in an iridium catalyst system, prepared from [IrCl(cod)]2, (S)-BINAP, NBu 4 BH4, gives with high enantioselectivity the corresponding A-hydroxylamines which are important biologically active compounds and precursors of amines (480). Further reduction of hydroxylamines to secondary amines or imines can be realized upon treatment with Fe/AcOH (479), or anhydrous titanium trichloride in tetrahydrofuran (THF) at room temperature (481). 

Scheme 24.12 Several pharmaceutically active compounds to have been synthesized via Rh-phospholane-mediated asymmetric hydrogenation.

Wink reported the use of bisphosphite ligands in the asymmetric hydrogenation of enamides (2-10% ee) [114]. In 1998, Selke synthesized a series of analogues based on 98a. Of these compounds, 147 (Fig. 27.14) was selected as ligand for the Rh-catalyzed hydrogenation of methyl (Z)-2-ace tamidocinnamate, though it induced only low enantioselectivity (13% ee) [115]. 

Fig. 32.15 Examples of biologically active compounds obtainable through asymmetric hydrogenation of/M

Asymmetric catalytic hydrogenation is one of the most efficient and convenient methods for preparing a wide range of enantiomerically pure compounds, and Ru-BINAP-catalyzed asymmetric hydrogenation of 2-arylacrylic acids has attracted a great deal of attention,11 as the chiral 2-arylpropionic acid products constitute an important class of nonsteroidal antiinflammatory drugs. 

Asymmetric Hydrogenation of Enol Esters. Prochiral ketones represent an important class of substrates. A broadly effective and highly enantioselective method for the asymmetric hydrogenation of ketones can produce many useful chiral alcohols. Alternatively, the asymmetric hydrogenation of enol esters to yield a-hydroxyl compounds provides another route to these important compounds. 

Allylic alcohol derivatives are quite useful in organic synthesis, so the asymmetric synthesis of such compounds via asymmetric hydrogenation of dienyl (especially enynyl) esters is desirable. The olefin functionality preserves diverse synthetic potential by either direct or remote functionalization. Boaz33 reported that enynyl ester and dienyl ester were preferred substrates for asymmetric hydrogenation using Rh-(Me-DuPhos) catalyst [Rh(I)-(R,R)-14], and products with extremely high enantioselectivity (>97%) were obtained (Schemes 6-11 and 6-12). 

Broene and Buchwald37 synthesized chiral titanocene compound 22 for the asymmetric hydrogenation of trisubstituted olefins. 

In contrast to the success in the synthesis of optically active amino acids and related compounds, only limited success has been achieved in the asymmetric synthesis of chiral amines or related compounds. One breakthrough is the asymmetric hydrogenation of arylenamides with Rh catalysts containing... 

When a commercially available C2-symmetric l,4 3,6-dianhydro-D-mannite 29 is chosen as the backbone, reaction of this diol compound with chlorophos-phoric acid diaryl ester gives a series of phosphorate ligands 30. These were tested using the asymmetric hydrogenation of dimethyl itaconate as a model... 

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