Chirality catalytic hydrogenation

A reaction that introduces a second chirality center into a starting material that already has one need not produce equal quantities of two possible diastereomers Con sider catalytic hydrogenation of 2 methyl(methylene)cyclohexane As you might expect both CIS and trans 1 2 dimethylcyclohexane are formed... 

Synthesis of the prototype begins with Friedel Crafts acetylation of salicylamide ( ). Bromination of the ketone (25) followed by displacement with amine gives the corresponding ami noketone ( ). Catalytic hydrogenation to the ami noalcohol completes the synthesis of labetolol (24). The presence of two chiral centers at remote positions leads to the two diastereomers being obtained in essentially equal amounts. 

In an indirect amination process, acyl halides are converted to amino acids. Reaction of the acyl halide with a chiral oxazolidinone leads to a chiral amide, which reacts with the N=N unit of a dialkyl azodicarboxylate [R"02C—N=N—CO2R ]. Hydrolysis and catalytic hydrogenation leads to an amino acid with good enantioselectivity. ... 

Finally, the chiral auxiliary was removed by a Birch reduction or a catalytic hydrogenation. After ring opening several optically active 6-aminohexanoic acids served as linkers in cyclic peptides as /1-turn mimetics (Table 12, Scheme 49) [51c],... 

The hydrogenation of a cinnamate was also investigated as a first step to determine kinetics and finally to come to a quantitative determination of kinetic models and parameters in asymmetric catalysis [64]. The enantiomeric excess of enantioselective catalytic hydrogenations is known to be dependent on pressure, chiral additives and mixing. Such dependences are often due to kinetics, demanding appropriate studies. 

Brunner et al. attached chiral branches to non-chiral catalytically active sites. With the aim to influence the enantioselectivity of transition metal catalyzed reactions they synthesized several dendritically enlarged diphosphines such as 81 [101] (Fig. 29). In situ prepared catalysts from [Rh(cod)Cl]2and81 have been tested in the hydrogenation of (a)-N-acetamidocinnamic acid. After 20 hours at 20 bar H2-pressure (Rh/substrate ratio 1 50) the desired product was obtained with an enantiomer ratio of 51 49. 

A similar strategy served to carry out the last step of an asymmetric synthesis of the alkaloid (—)-cryptopleurine 12. Compound 331, prepared from the known chiral starting material (l )-( )-4-(tributylstannyl)but-3-en-2-ol, underwent cross-metathesis to 332 in the presence of Grubbs second-generation catalyst. Catalytic hydrogenation of the double bond in 332 with simultaneous N-deprotection, followed by acetate saponification and cyclization under Mitsunobu conditions, gave the piperidine derivative 333, which was transformed into (—)-cryptopleurine by reaction with formaldehyde in the presence of acid (Scheme 73) <2004JOC3144>. 

The catalytic hydrogenation of the C=N bond of imines has attracted considerable attention, and a useful review covering the literature until 1996 has been reported by James.110 Chiral [Pg.91]

Some general reviews on hydrogenation using transition metal complexes that have appeared within the last five years are listed (4-7), as well as general reviews on asymmetric hydrogenation (8-10) and some dealing specifically with chiral rhodium-phosphine catalysts (11-13). The topic of catalysis by supported transition metal complexes has also been well reviewed (6, 14-29), and reviews on molecular metal cluster systems, that include aspects of catalytic hydrogenations, have appeared (30-34). 

The synthesis of cationic rhodium complexes constitutes another important contribution of the late 1960s. The preparation of cationic complexes of formula [Rh(diene)(PR3)2]+ was reported by several laboratories in the period 1968-1970 [17, 18]. Osborn and coworkers made the important discovery that these complexes, when treated with molecular hydrogen, yield [RhH2(PR3)2(S)2]+ (S = sol-vent). These rhodium(III) complexes function as homogeneous hydrogenation catalysts under mild conditions for the reduction of alkenes, dienes, alkynes, and ketones [17, 19]. Related complexes with chiral diphosphines have been very important in modern enantioselective catalytic hydrogenations (see Section 1.1.6). 

Kagan et al. were the first to report the corresponding enantioselective catalytic hydrogenation using chiral metallocene derivatives [94, 95]. By using menthyl- and neomenthyl-substituted cyclopentadienyl titanium derivatives in the presence of activators (Scheme 6.5) [96], these authors observed low ee-values (7-14.9%) for the catalytic hydrogenation of 2-phenyl-l-butene into 2-phenylbutane. In contrast, no enantiomeric excess was obtained with the corresponding zirconocene derivatives. 

Table 34.8 Typical ranges of reaction conditions, optical yields, turnover frequencies (TOF) and substratexatalyst ratios (SCR) for the hydrogenation of C = N functions using various chiral catalytic systems.

Chiral Phosphine Ligands for Homogeneous Asymmetric Catalytic Hydrogenation... 

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. 

Much effort has been devoted to investigating chiral phosphine ligands for their synthesis and asymmetric catalytic hydrogenation potential, and such chiral phosphine ligands have been extensively used for catalytic asymmetric hydrogenation, both academically and industrially.14... 

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