Asymmetric catalysis ketone reduction

Sih, C.J., Chen, C.S. Microbial asymmetric catalysis - enantioselection reduction of ketones. Angew. Chem. Int. Ed. Engl. 1984, 23 570-578. 

Microbial Asymmetric Catalysis - Enantioselective Reduction of Ketones"... 

The chemoenzymatic synthesis of chiral alcohols is a field of major interest within biocatalytic asymmetric conversions. A convenient access to secondary highly enan-tiomerically enriched alcohols is the usage of alcohol dehydrogenases (ADHs) (ketoreductases) for the stereoselective reduction of prochiral ketones. Here, as in many other cases in asymmetric catalysis, enzymes are not always only an alternative to chemical possibilities, but are rather complementary. Albeit biocatalysts might sometimes seem to be more environmentally friendly, asymmetric ketone reduction... 

Asymmetric catalysis undertook a quantum leap with the discovery of ruthenium and rhodium catalysts based on the atropisomeric bisphosphine, BINAP (3a). These catalysts have displayed remarkable versatility and enantioselectivity in the asymmetric reduction and isomerization of a,P- and y-keto esters functionalized ketones allylic alcohols and amines oc,P-unsaturated carboxylic acids and enamides. Asymmetric transformation with these catalysts has been extensively studied and reviewed.81315 3536 The key feature of BINAP is the rigidity of the ligand during coordination on a transition metal center, which is critical during enantiofacial selection of the substrate by the catalyst. Several industrial processes currently use these technologies, whereas a number of other opportunities show potential for scale up. 

The asymmetric catalytic reduction of ketones (R2C=0) and imines (R2C=NR) with certain organohydrosilanes and transition-metal catalysts is named hydrosilylation and has been recognized as a versatile method providing optically active secondary alcohols and primary or secondary amines (Scheme 1) [1]. In this decade, high enantioselectivity over 90% has been realized by several catalytic systems [2,3]. Therefore the hydrosilylation can achieve a sufficient level to be a preparative method for the asymmetric reduction of double bond substrates. In addition, the manipulative feasibility of the catalytic hydrosilylation has played a major role as a probe reaction of asymmetric catalysis, so that the potential of newly designed chiral ligands and catalysts can be continuously scrutinized. 

Only partial solutions have been provided thus far to many of the most important transformations amenable to asymmetric catalysis. For example, no generally effective methods exist yet for enantioselective epoxidation or aziridination of terminal olefins, or for hydroxylation of C-H bonds of any type. Despite the enormous advances in asymmetric hydrogenation catalysis, highly enantioselective reduction of dialkyl ketones remains elusive [9]. And as far as asymmetric C-C bond-forming reactions are concerned, the list of successful systems is certainly shorter than the list of reactions waiting to be developed. 

Sih CJ, Chen C-S (1984) Microbial asymmetric catalysis - Enantio-selective reduction of ketones. Angew Chem Int Ed Engl 23 570-578 Slama J, Oruganti SR, Kaiser ET (1981) Semisynthetic enzymes Synthesis of a new flavopapain with high catalytic efficiency. J Am Chem Soc 103 6211-6213... 

Alnminium alkoxides have long been used as catalysts for the reduction of aldehydes or ketones by secondary alcohols and recently lanthanide alkoxides were reported to act similarly in addition to catalysing the epoxidation of allylic alcohols with tert-butyl hydroperoxide. Aluminium alkoxides have also been used to catalyse the conversion of aldehydes to alkylesters (Tischtchenko reaction). A review gives a fascinating account of the use of heterometal alkoxides in asymmetric catalysis. 

Chiral oxazaborolidine catalysts were applied in various enantioselective transformations including reduction of highly functionalized ketones/ oximes or imines/ Diels-Alder reactions/ cycloadditions/ Michael additions, and other reactions. These catalysts are surprisingly small molecules compared to the practically efficient chiral phosphoric acids, cinchona alkaloids, or (thio)ureas hence, their effectiveness in asymmetric catalysis demonstrates that huge substituents or extensive hydrogen bond networks are not absolutely essential for successful as5unmetric organocatalysis. 

Kejrwords Dynamic kinetic asymmetric transformation (DYKAT) Dynamic kinetic resolution (DKR) Hydrogenation Imine reduction Ketone reduction Mechanism of carbonyl reduction Mechanism of imine reduction Mechanism of dUiydrogen activation Ruthenium catalysis Shvo s catalyst Transfer hydrogenation... 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

TABLE 12. The asymmetric reduction of prochiral ketones under catalysis of chiral urea derivative 8173 (in all reactions 5% catalyst was used)... 

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. ... 

An early report of a promising level of asymmetric induction in the reduction of ketones by chiral PTC [62a] was disputed [26b,60c]. Several reviews concerning hydrogenation by enantioselective catalysis have appeared [5j-l]. 

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