Chiral ligands asymmetric hydrogenation

Asymmetric hydrogenations, hydrosilylations, and the like can be carried out using chiral metal catalysts. Chiral phosphines are often used as ligands to render the catalyst chiral. Catalytic asymmetric hydrogenation has remained an extremely active area of research for several decades. 

When insertion of the coordinated prochiral olefin to a metal alkyl or a metal hydride takes place, the stereochemistry of the substituted carbon atom is determined as either R or S enantiomer. When the chiral alkyl group is reductively eliminated with the hydrido ligand, asymmetric hydrogenation of an olefin producing enatiomeric excess of one of the optical isomers can be achieved. 

Catalytic asymmetric hydrogenation was one of the first enantioselective synthetic methods used industrially (82). 2,2 -Bis(diarylphosphino)-l,l -binaphthyl (BINAP) is a chiral ligand which possesses a Cg plane of symmetry (Fig. 9). Steric interactions prevent interconversion of the (R)- and (3)-BINAP. Coordination of BINAP with a transition metal such as mthenium or rhodium produces a chiral hydrogenation catalyst capable of inducing a high degree of enantiofacial selectivity (83). Naproxen (41) is produced in 97% ee by... 

Efficient enantioselective asymmetric hydrogenation of prochiral ketones and olefins has been accompHshed under mild reaction conditions at low (0.01— 0.001 mol %) catalyst concentrations using rhodium catalysts containing chiral ligands (140,141). Practical synthesis of several optically active natural... 

Four general methods have been used for obtaining chiral ligands resolution of a racemic mixture, use of a chiral naturally occurring product 33), and asymmetric homogeneous or heterogeneous hydrogenation. 

The influence of the concentration of hydrogen in [BMIM][PFg] and [BMIM][BF4] on the asymmetric hydrogenation of a-acetamidocinnamic acid catalyzed by rhodium complexes bearing a chiral ligand has been investigated. FFydrogen was found to be four times more soluble in the [BFJ -based salt than in the [PFg] -based one. 

In 1968,Horner et al. [22] and Knowles and Sabacky [23] independently demonstrated that low but definite enantiomeric excesses (up to 15% ee) were produced in the rhodium-catalyzed asymmetric hydrogenation of simple alkenes using methylpropylphenylphosphine 7 as chiral ligand (Scheme 1). 

The Rh(I)-catalyzed asymmetric hydrogenation of dimethyl 1-benzoyloxy-ethenephosphonate 2 using f-Bu-BisP as the chiral ligand gave the corresponding (S)-product in 88% ee (Scheme 27) [120], enantioselectivity being comparable to those observed by Burk et al. [121]. 

In recent years, the catalytic asymmetric hydrogenation of a-acylamino acrylic or cinnamic acid derivatives has been widely investigated as a method for preparing chiral a-amino acids, and considerable efforts have been devoted for developing new chiral ligands and complexes to this end. In this context, simple chiral phosphinous amides as well as chiral bis(aminophosphanes) have found notorious applications as ligands in Rh(I) complexes, which have been used in the asymmetric hydrogenation of a-acylamino acrylic acid derivatives (Scheme 43). 

In 2004, Bolm et al. reported the use of chiral iridium complexes with chelating phosphinyl-imidazolylidene ligands in asymmetric hydrogenation of functionalized and simple alkenes with up to 89% ee [17]. These complexes were synthesized from the planar chiral [2.2]paracyclophane-based imida-zolium salts 74a-c with an imidazolylidenyl and a diphenylphosphino substituent in pseudo ortho positions of the [2.2]paracyclophane (Scheme 48). Treatment of 74a-c with t-BuOLi or t-BuOK in THF and subsequent reaction of the in situ formed carbenes with [Ir(cod)Cl]2 followed by anion exchange with NaBARF afforded complexes (Rp)-75a-c in 54-91% yield. The chela-... 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

On the other hand, James reported, in 1976, the use of a chiral sulfoxide as a ligand of ruthenium for the asymmetric hydrogenation of itaconic acid, providing a low enantioselectivity of 12% ee (Scheme 8.23). ... 

In recent years, the asymmetric hydrogenation of prochiral olefins have been developed in the presence of various chiral sulfur-containing ligands combined with rhodium, iridium or more rarely ruthenium catalysts. The best results have been obtained by using S/P ligands, with enantioselectivities of up to 99% ee in... 

In another context, chiral thioimidazolidine ligands have been successfully applied to the ruthenium-catalysed asymmetric hydrogen transfer of several aryl ketones by Kim et al., furnishing the corresponding chiral alcohols with high yields and enantioselectivities of up to 77% ee (Scheme 9.12). ... 

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