Asymmetric reactions ketone reduction

The strategy for the asymmetric reductive acylation of ketones was extended to ketoximes (Scheme 9). The asymmetric reactions of ketoximes were performed with CALB and Pd/C in the presence of hydrogen, diisopropylethylamine, and ethyl acetate in toluene at 60° C for 5 days (Table 20) In comparison to the direct DKR of amines, the yields of chiral amides increased significantly. Diisopropylethylamine was responsible for the increase in yields. However, the major factor would be the slow generation of amines, which maintains the amine concentration low enough to suppress side reactions including the reductive aminafion. Disappointingly, this process is limited to benzylic amines. Additionally, low turnover frequencies also need to be overcome. 

Addition of triethylamine to the oxazaborolidine reaction system can significantly increase the enantioselectivity, especially in dialkyl ketone reductions.79 In 1987, Corey et al.80 reported that the diphenyl derivatives of 79a afford excellent enantioselectivity (>95%) in the asymmetric catalytic reduction of various ketones. This oxazaborolidine-type catalyst was named the CBS system based on the authors names (Corey, Bakshi, and Shibata). Soon after, Corey s group81 reported that another fi-methyl oxazaborolidine 79b (Fig. 6-6) was easier to prepare and to handle. The enantioselectivity of the 79b-catalyzed reaction is comparable with that of the reaction mediated by 79a (Scheme 6-36).81 The -naphthyl derivative 82 also affords high enantioselectivity.78 As a general procedure, oxazaborolidine catalysts may be used in 5-10 mol%... 

The asymmetric formation of industrially useful diaryl methanols can be realized through either the addition of aryl nucleophiles to aromatic aldehydes or the reduction of diaryl ketones. The latter route is frequently the more desirable, as the starting materials are often inexpensive and readily available and nonselective background reactions are not as common. For good enantioselectivity, chemical catalysts of diaryl ketone reductions require large steric or electronic differentiation between the two aryl components of the substrate and, as a result, have substantially limited applicability. In contrast, recent work has shown commercially available ketoreductase enzymes to have excellent results with a much broader range of substrates in reactions that are very easy to operate (Figure 9.6). ... 

Two types of asymmetric reactions were conducted synthesis of styrene oxide and reduction of olefinic ketones. 

Kinetic and molecular modeling studies support the view that asymmetric ketone reduction proceeds through reaction of the borolane with a complex formed by coordination of the borolanyl mesylate syn to the smaller alkyl group (R ) of the ketone (eq 8). After reaction is complete, the chiral borolane moiety is recovered as a crystalline complex with 2-amino-2-methyl-l-propanol (eq 9). 

Asymmetric MPV type reduction can be achieved by using a chiral Sm(III) complex 38 (Scheme 29) [93]. Several aryl methyl ketones are reduced in an excellent optical yield, up to 97%. Electronic properties of substrates profoundly affect the reactivity. For example, a p-chloro substituent in the benzene ring accelerates the reaction, whereas a p-methoxy substituent decelerates the reduction. The presence of an o-chloro or o-methoxy group effectively enhances the... 

Table 7.4. Selected examples of asymmetric ketone reductions using Runci2-BINAP. Reactions were run at room temperature and 50-100 atm unless otherwise noted. Yields were determined spectroscopically unless noted.

Both enantiomers of 1,1 -bi-2-naphthol are widely used for various applications 1) chiral inducing agents for catalytic, asymmetric reactions such as the Diels-Alder reaction,2 ene reaction,3 or as Lewis acids 4 2) enantioselective reduction of ketones 5 3) synthesis of chiral macrocycles6 and other interesting compounds.7 Previously... 

The asymmetric reaction of cyclic ketones can be performed with chiral bi-naphthylphosphines (Eq. 8) [47-50]. The reaction of acetophenones with ortho-bromonitrobenzenes followed by reduction affords indole derivatives (Eq. 9)... 

Life uses enzymes to catalyse asymmetric reactions, so the question is—can chemists The answer is yes, and there are many enzymes that can be produced in quantities large enough to be used in the catalytic synthesis of enantiomerically pure molecules. This field—known as biocatalysis—melds ideas in chemistry and biology, and we do not have the space here to discuss it in detail. We leave you with just one example the reduction of a ketone to an alcohol with an enzyme known as a ketoreductase. 

OH) with aldehydes 9 in the homogeneous conditions (DMF or DMSO) (Scheme 10.1). Furthermore, PEG-supported catalyst 20a could be recovered by precipitation from the DMF solution with ether and reused in the same reactions without reduction of enantiomeric excesses of products 10 (R = OH). It also appeared applicable to asymmetric iminoaldol (Mannich) reactions to afford p-aminoketones 16 (R = Ar) (Scheme 10.3) and to the enantioselective Michael/aldol cascade reaction resulting in the S3mthesis of Wieland-Mischler ketone 28b, an important precursor of some other natural compounds (Scheme 10.6). Diastereo- and enantioselectivities of these reactions were close to the corresponding data for proline-catalysed reactions. 

Metal alkoxides have promising role in catalytic reactions. In this chapter, we briefly review the history, chciracteristics, cuid synthesis routes of metal alkoxide and then discuss some catalytic processes that are performed with them. These processes include polymerization of different olefin oxides and cyclic esters asymmetric reduction of aldehydes and ketones oxidation of sulfides and olefins and a variety of other asymmetric reactions. The rest of the chapter discusses the characteristics of these catalytic systems from different points of view. 

Directed and Asymmetric Reduction The principles of directed and asymmetric reactions were first developed for hydrogenation, as discussed in Section 9.2. Asymmetric hydrosilation of ketones can now be carried out cata-lytically with rhodium complexes of diop (9.22). The new chiral ligand Et-duPHOS, made by Burk at du Pont, allows chiral amination of ketones via Eq. 14.50. Note how the use of the hydrazone generates an amide carbonyl to act as a ligand, as is known to favor high e.e. (see Section 9.2). Noyori s powerful BINAP ligand has been applied to a large number of asymmetric reactions. 

In addition, metal-catalyzed carbon-carbon bond formation and subsequent enzymatic transformations turned out to be compatible. This has been demonstrated by the Groger and Hummel groups [59], combining the Suzuki reaction as an example for a paUadium-catalyzed cross<oupling reaction with an asymmetric ADH-catalyzed ketone reduction in an aqueous reaction medium (Scheme 19.24). In such a one-pot process, the amount of boronic acid turned out to be critical because of strong inhibition of the enzyme. Thus, a two-step one-pot strategy was developed which was based on the use of 1 equiv of boronic acid in the Suzuki reaction, and addition of the enzyme directly to the reaction mixture after consumption... 

The development of a Heck reaction in aqueous media, enabling a one-pot process with both reaction steps (Heck reaction and biotransformation) running in aqueous media, was also reported by Cacchi and coworkers [65]. This type of Heck reaction is based on the use of a phosphine-free perfluoro-tagged palladium nanoparticle. After detailed catalyst characterization and process development, Cacchi and coworkers also succeeded in combining this Heck reaction efficiently with the subsequent asymmetric ketone reduction toward a one-pot process. A representative example is shown in Scheme 19.25. The enzymatic process turned out to be very compatible with the Heck reaction, and the desired allylic alcohol products were obtained in yields of up to 92% and with excellent enantioselectivities of >99% ee in aU cases. This two-step one-pot process was, for example, successfully applied for the synthesis of (k)-(—)-rhododendrol ((J )-81) in 90% yield and with excellent (>99%) ee (Scheme 19.25) [65]. 

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