Asymmetric reduction prochiral ketones

In the above cases, an optically active reducing agent or catalyst interacts with a prochiral substrate. Asymmetric reduction of ketones has also been achieved with an achiral reducing agent, if the ketone is complexed to an optically active transition metal Lewis acid. ... 

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],... 

In the asymmetric reduction of ketones, stereodifferentiation has been explained in terms of the steric recognition of two substituents on the prochiral carbon by chirally modified reducing agents40. Enantiomeric excesses for the reduction of dialkyl ketones, therefore, are low because of the little differences in the bulkiness of the two alkyl groups40. In the reduction of ketoxime ethers, however, the prochiral carbon atom does not play a central role for the stereoselectivity, and dialkyl ketoxime ethers are reduced in the same enantiomeric excess as are aryl alkyl ketoxime ethers. Reduction of the oxime benzyl ethers of (E)- and (Z)-2-octanone with borane in THF and the chiral auxiliary (1 R,2S) 26 gave (S)- and (R)-2-aminooctane in 80 and 79% ee, respectively39. 

Asymmetric reduction of ketones.2 A reducing agent prepared by treatment of a mixture of SnCl2 and (S)-l-[l-methyl-2-pyrrolidinyl]methylpiperidine (11, 525, 12, 490) with DIBAH effects asymmetric reduction of prochiral ketones in 60-80% ee (equation I). 

Asymmetric reduction of ketones. Lithium aluminum hydride, after partial decomposition with 1 equiv. of 1 and an amine additive such as N-benzylmethylamine, can effect asymmetric reduction of prochiral ketones at temperatures of —20°. The highest... 

Asymmetric reduction of ketones. Chiral ketals 2, obtained by reaction of 1 with prochiral ketones, are reduced diastereoselectively to 3 by several aluminum hydride reagents, the most selective of which is dibromoalane (LiAIHj-AIBr, 1 3). Oxidation and cleavage of the chiral auxiliary furnishes optically active alcohols (4) in optical yields of 78-96% ee (equation 1). 

Asymmetric Reduction of Ketones. A reagent system consisting of (/ ,/ )-2,5-dimethylborolane (1.0 equiv) and the corresponding borolanyl mesylate (0.2 equiv) reduces a variety of prochiral ketones with asymmetric induction in the range of 80-100% ee. The reagent system is prepared in situ by addition of 1.4 equiv of Methanesulfonic Acid to a solution of the lithium dihydridoborate, prepared as in eq 5 above (eq 7). 

Asymmetric reduction of ketones.1 Lithium aluminium hydride in conjunction with this chiral ligand reduces prochiral aromatic ketones to (S)-secondary alcohols in 90-95% optical yields. Optical yields are lower (10-40% ee) in the case of alkyl aryl ketones. It is superior to (S)-2-(anilinomethyl)pyrrolidine for this reduction. Evidently the two methyl groups enhance the enantioselectivity. 

Asymmetric reduction of ketones.2 Both Alpine-Borane and B-chlorodiisopino-campheylborane (Ipc2BCl) have one main defect for asymmetric reduction of prochiral ketones they show little cnantiosclectivity in reduction of dialkyl ketones in which the alkyl groups arc similar in size. This problem is now solved by reductions with Eap2BCl (1). Thus acctylcyclohexanc is reduced by 1 in 97% ce and isopropyl methyl ketone is reduced in 95% ee (65% yield). 

Asymmetric reduction of ketones by hydrosilylation in the presence of a chiral catalyst followed by hydrolysis has been studied by several research groups independently. In this Section, results so far obtained are properly compiled and plausible mechanisms of the asymmetric hydrosilylation of prochiral ketones are discussed. 

Asymmetric reduction of prochiral ketones is one of most efficient method of the introduction of chirality in the synthesis of non-racemic biologically active compounds. Derived from chiral (S)-diphenyl prolinole the amino borate ester 1 has been prepared, fully characterized and used as highly effective catalyst for asymmetric reduction of ketons with borane. The optically pure alcohols 3 have been prepared using only 1 mol % of catalyst 1 in enantioselectivity up to 97%. 

Chiral aluminium hydride for the asymmetric reduction of prochiral ketones... 

In 2000, Woodward et al. reported that LiGaH4, in combination with the S/ 0-chelate, 2-hydroxy-2 -mercapto-1,1 -binaphthyl (MTBH2), formed an active catalyst for the asymmetric reduction of prochiral ketones with catecholborane as the hydride source (Scheme 10.65). The enantioface differentiation was on the basis of the steric requirements of the ketone substituents. Aryl w-alkyl ketones were reduced in enantioselectivities of 90-93% ee, whereas alkyl methyl ketones e.g. i-Pr, Cy, t-Bu) gave lower enantioselectivities of 60-72% ee. 

Enantiometrically pure alcohols are important and valuable intermediates in the synthesis of pharmaceuticals and other fine chemicals. A variety of synthetic methods have been developed to obtain optically pure alcohols. Among these methods, a straightforward approach is the reduction of prochiral ketones to chiral alcohols. In this context, varieties of chiral metal complexes have been developed as catalysts in asymmetric ketone reductions [ 1-3]. However, in many cases, difficulties remain in the process operation, and in obtaining sufficient enantiomeric purity and productivity [2,3]. In addition, residual metal in the products originating from the metal catalyst presents another challenge because of the ever more stringent regulatory restrictions on the level of metals allowed in pharmaceutical products [4]. An alternative to the chemical asymmetric reduction processes is biocatalytic transformation, which offers... 

Complexation of (124) and (125) with [ Rh(COD)Cl 2] in the presence of Si(OEt)4, followed by sol-gel hydrolysis condensation, afforded new catalytic chiral hybrid material. The catalytic activities and selectivities of these solid materials have been studied in the asymmetric hydro-gen-transfer reduction of prochiral ketones and compared to that of the homogeneous rhodium complexes containing the same ligands (124) and (125) 307... 

The asymmetric organosilane reduction of prochiral ketones has been studied as an alternative to the asymmetric hydrogenation approach. A wide variety of chiral ligand systems in combination with transition metals can be employed for this purpose. The majority of these result in good to excellent chemical yields of the corresponding alcohols along with a trend for better ee results with aryl alkyl ketones than with prochiral dialkyl ketones. 

As an extension of the asymmetric hydrogenation of prochiral ketones to enantiomerically enriched alcohols, the reduction of imines has been a topic of interest in obtaining chiral amines of high enantiomeric purity. Several entries to enantiomerically enriched amines based on the approaches outlined above are available. These asymmetric hydrogenations have proved to be more difficult than those for prochiral ketones, but nevertheless show good promise. 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

TABLE 6-9. Asymmetric Reduction of Prochiral Ketones Using 10 mol% of ( + )-94... 

In summary, many attempts have been made at achieving enantioselective reduction of ketones. Modified lithium aluminum hydride as well as the ox-azaborolidine approach have proved to be very successful. Asymmetric hydrogenation catalyzed by a chiral ligand-coordinated transition metal complex also gives good results. Figure 6-7 lists some of the most useful chiral compounds relevant to the enantioselective reduction of prochiral ketones, and interested readers may find the corresponding applications in a number of review articles.77,96,97... 

Various catalytic or stoichiometric asymmetric syntheses and resolutions offer excellent approaches to the chiral co-side chain. Among these methods, kinetic resolution by Sharpless epoxidation,14 amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde,15 lithium acetylide addition to an alkanal,16 reduction of the corresponding prochiral ketones,17 and BINAL-H reduction18 are all worth mentioning. 

The quality of the ligand can be determined by performing an asymmetric reduction reaction on prochiral ketones according to the following procedure. 

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