Hydrogenation with chiral catalysts

Amino ketones and their hydrochloride salts can be effectively hydrogenated with chiral rhodium catalysts (Table 33.5). The rhodium precatalysts, when combined with chiral phosphorus ligands such as BPPFOH 4 [20b], hydroxyproline derivatives ligands [20-24], Cy,Cy-oxo-ProNOP 15, Cp,Cp-oxoProNOP 16, and... 

Enantioselectivity can also be achieved with chiral catalysts. For example, additions of /V - aery I oy I o x azo I inones can be made enantioselective using Sc(03SCF3)3 in the presence of a BINOL ligand.63 Optimized conditions involved use of 5-20 mol % of the catalyst along with a hindered amine such as cis-1,2,6-trimcthylpipcridine. A hexacoordinate transition state in which the amine is hydrogen-bonded to the BINOL has been proposed. 

In conclusion, we have found a convenient and practical method for the selective reduction of C=0 bond of a wide spectrum of a-keto-)S, -unsaturated esters with Ru(p-cymene)(TsDPEN) as catalyst. The transition metal catalyzed transfer hydrogenation reaction with good selectivity and high efficiency offers possibilities to provide the optically active a-hydroxy-/l, y-unsaturated esters with chiral catalysts. Table 3.8 gives different substrates that can be reduced with Ru(p-cymene) (TsDPEN) complex in isopropyl alcohol. 

Trimethylindolenine was hydrogenated with a catalyst consisting of [IrCl(COD)]2, (R,R)-BICP, and phthalimide in CH2C12 under 68 atm of H2 to afford the chiral cyclic amine in 95.1% ee (Scheme 9) [20]. The addition of phthalimide remarkably increased the optical yield [21]. Hydrogenation of a dihydroisoquinoline compound with a neutral (R)-BINAP/Ir complex in... 

Besides the production of (R)-l-phenylethanol as a fragrance,198 various pharmaceutically important chiral compounds have been produced at various lab scales by asymmetric hydrogenation with JST catalysts. These compounds include a P1-receptor antagonist denopamine hydrochloride (149),191 antidepressant fluoxetine hydrochloride (150),191 antipsychotic BMS 181100 (151),191 serotonin and norepinephrine inhibitor duloxetine (129),164 antihistaminic and anticholinergic orphenadrine (152),192 and antihistaminic neobenodine (153).192... 

For the aziridination of 1,3-dienes, copper catalysis gave better yields of A-tosyl-2-alkenyl aziridines with 1,3-cyclooctadiene, 1,4-addition occurred exclusively (50%) [46]. Good results were also obtained on rhodium catalysed decomposition of PhI=NNs (Ns = p-nitrophenylsulphonyl) with some alkenes the aziridination was stereospecific, whereas with chiral catalysts asymmetric induction (up to 73% ee) was achieved. However, cyclohexene gave predominantly (70%) a product derived from nitrene insertion into an allylic carbon-hydrogen bond [47]. 

Genet, J. P. Recent developments in asymmetric hydrogenation with chiral Ru(ll) catalysts and synthetic applications to biologically active... 

For enantioselective hydrogenations with chiral cyclopentadienyl zirconium catalysts, sec ... 

Two factors contribute to the success of this reaction the outstanding enantio-selectivity achieved, and efficiency of the catalyst (i.e, high turnover). The above analysis emphasizes only the former, but the latter also varies with the nature of the chiral bisphosphine ligand and the structure of the substrate. The structural features of the substrate and the catalyst are mutually optimal in the example cited above. Perturbation of any of these features usually lowers either the enantioselectivity or the turnover rate. The range of substrates that are amenable to asymmetric hydrogenation with this catalyst system is, therefore, limited. Figure 7.9 illustrates the classes of substrate that can be accomodated by cationic rhodium bisphosphine catalysts [104]. For a more extensive summary, see ref. [110]. 

William S. Knowles (United States) and Rybji Noyori (Japan) for their work on chirally catalyzed hydrogenation reactions and K. Barry Sharpless (United States) for his work on chirally catalyzed oxidation reactions. Half of this prize was awarded to Knowles and Noyori for their work with chiral catalysts that chirally catalyzed hydrogenation reactions, or reactions in which two hydrogen atoms are added. This work found applications in pharmaceutical production soon after its discovery. Sharpless was awarded the other half of this prize for developing chiral catalysts to carry out oxidation reactions, which represent another important class of reactions in organic synthesis. 

Enamides can also be efficiently hydrogenated with chiral Rh-complexes. The Rh complexes of Ph-BPE,f > BICP, TangPhos, SIPHOS,f and others have been shown to catalyze the hydrogenation of a mixture of (E) and (Z) P-methyl-a-phenylenamides 161 with excellent enantioselectivities. The hydrogenation of 2- and 3-substituted A -acetylindoles with the Ph-TRAP-Rh system was also possible with high ee. (R,S,S,R)-D10P was shown to be an excellent catalyst system for a variety of aromatic enamides. ... 

The other reactions occurring via intramolecular flve-manbered ring intermediates are decarbonylative cleavages with organoruthenium catalysts [119], asymmetric hydrogenations with rhodium catalysts [120], reductive eliminations with rhodium catalysts [121], one-pot preparations of chiral homoaUyUc alcohol or... 

Catalytic Hydrogenation with Chiral, Nonracemic Catalysts... 

ASYMMETRIC HYDROGENATION WITH CHIRAL RUTHENIUM CATALYSTS... 

Very recently, Klankermayer and co-workers described the first enantioselec-tive hydrogenation with chiral FLP catalyst that afforded enantioselectivities better than 80% ee [40], Although this catalyst was not strictly a bifunctional FLP catalyst, the result is mentioned here since the covalent, enantioselective FLP catalysts are very likely the next step in FLP catalysis. The Klankermayer catalyst 115 was able to reduce a number of imines enantioselectively to amines (Scheme 6.20). 

---