Metal-catalyzed asymmetric reductions

Cinchona Alkaloids as Chirality Transmitters in Metal-Catalyzed Asymmetric Reductions... 

As shown in Figure 1.26, a chiral Sm(III) complex catalyzes asymmetric reduction of aromatic ketones in 2-propanol with high enantioselectivity. Unlike other late-transition-metal catalysis, the hydrogen at C2 of 2-propanol directly migrates onto the carbonyl carbon of substrate via a six-membered transition state 26A, as seen in the Meerwein-Ponndorf-Verley reduction. ... 

On the contrary, to achieve a successful cinchona-catalyzed asymmetric oxidation chemistry, cinchona-catalyzed asymmetric reduction has been explored very little despite the importance of this reaction. Previous reports on this subject are restricted to the reduction of aromatic ketones and, moreover, the enantioselectivities achieved to date remain far from satisfactory when compared with metal catalysis. 

In contrast to asymmetric oxidation chemistry, cinchona-catalyzed asymmetric reduction reactions have been explored very little, despite the importance of this reaction. Previous reports on this topic are restricted to the reduction of aromatic ketones, and the enantioselectivities achieved to date remain far from satisfactory when compared with metal catalysis. Moreover, Hantsch esters, another type of useful organic hydrides, have not yet been studied in combination with cinchona catalysts. However, as is well known, the structures of cinchona alkaloids are easily modifiable, thus permitting the easy tuning of the reaction course. The successful use of cinchona catalysts for this reaction will therefore likely be reported in the very near future. 

Transition metal catalyzed asymmetric hydrocarboration reactions are addition reactions forming one C—C and one C—H bond. Prominent examples are hydrovinylation, hydroformylation, hydroacylation, hydrocarboxylation, and hydrocyanation. Various related conversions, such as hydroalkylation, hydroarylation, conjugate addition, reductive dimerization, and metal induced ene reactions are collected in Section 1.5.8.2.6. dealing with miscellaneous methods of this type. Some of these methods are not exclusively mediated by metal catalysts and therefore are also covered in other sections of this volume. 

Scheme 7.10. Titanocene catalyzed asymmetric reduction of imines [85], In the accompanying discussion, the catalyst shown is designated the S,S enantiomer, in accord with the CIP rules for describing metal arenes [88]. This is a different designation than that used by Buchwald, however. ...

These examples were followed with a continuous stream of ligands (that continues to this day cf. ref. [66,105,107,108,118-120]) that were tested with rhodium and other metals in asymmetric reductions and other reactions catalyzed by transition metals [102-104,121]. Simultaneously, studies of the mechanism of the asymmetric hydrogenation were pursued, most agressively in the labs of Halpem... 

Chiral phosphines are widely used as auxiliaries for various metal-catalyzed asymmetric reactions and can be prepared from stable phosphine-borane complexes. Secondary P-chiral phos-phine-boranes can be prepared by reductive lithiation of the corresponding tertiary phosphine-borane using LN (eq Likewise, P-chiral tertiary phosphine ligands can be produced by the reductive lithiation of phosphinite-boranes followed by alkylation, both proceeding with retention of configuration (eq 18). ... 

The most efficient approach is probably the direct recycling of alanine from pymvate via NADH-dependent reduction in presence of ammonia catalyzed by alanine dehydrogenase. Overall, this sequence resembles a metal-fiee asymmetric reductive amination, which only requires ammonia and a low-cost reducing agent for NAD(P)H-recycling in molar amounts [1739]. 

Asymmetric hydrosilylation of ketones and ketoimines has been demonstrated in the absence of transition metal catalysts. Using catalytic amounts of chiral-alkoxide Lewis bases such as binaphthol (BINOL), Kagan was able to facilitate the asymmetric reduction of ketones (eq 19). This process is believed to arise from activation of the triethoxysilane by mono-alkoxide addition to give an activated pentavalent intermediate, which can undergo coordination of an aldehyde. This highly ordered hexacoordinate transition state directs reduction in an asymmetric manner, with subsequent catalyst regeneration. Brook was able to facilitate a similar tactic for asymmetric reduction by employing histidine as a bi-dentate Lewis base activator of triethoxysilane. A similar chiral lithium-alkoxide-catalyzed asymmetric reduction of imines was demonstrated by Hosomi with the di-lithio salt of BINOL and trimethoxysilane. ... 

Pu and co-workers incorporated atropisomeric binaphthols in polymer matrixes constituted of binaphthyl units, the macromolecular chiral ligands obtained being successfully used in numerous enantioselective metal-catalyzed reactions,97-99 such as asymmetric addition of dialkylzinc reagents to aldehydes.99 Recently, they also synthesized a stereoregular polymeric BINAP ligand by a Suzuki coupling of the (R)-BINAP oxide, followed by a reduction with trichlorosilane (Figure 10).100... 

Boronic esters have been used in a wide range of transformations. These useful reagents have been transformed into numerous functional groups and are essential reagents for several C-C bond-forming reactions. Transition metal-catalyzed hydroboration of olefins often leads to mixtures of branched and linear products. Several groups have reported asymmetric reductions of vinyl boronic esters [50-52] with chiral rhodium P,P complexes however, the first iridium-catalyzed reduction was reported by Paptchikhine et al (Scheme 10) [53]. 

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

Catalysis in general and asymmetric catalysis in particular are at the forefront of chemical research [1], Their impact on industrial production can hardly be overestimated and is likely to increase further [2]. However, the high degree of sophistication reached in many respects may hide the simple notion that there still remain fairly large domains in preparative organic chemistry in which no catalytic alternatives to well-established stoichiometric transformations yet exist. The following account is intended to put into perspective some pioneering studies which address this problem and try to develop new concepts for metal-catalyzed reductive bond formations [3]. 

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