Stereoselectivity reduction of ketones

A noteworthy development is the use of KH for complexing alkylboranes and alkoxyboranes to form various boron hydrides used as reducing agents in the pharmaceutical industry. Potassium tri-j -butylborohydride [54575-50-7] KB(CH(CH2)C2H )2H, and potassium trisiamylborohydride [67966-25-0] KB(CH(CH2)CH(CH2)2)3H, are usefiil for the stereoselective reduction of ketones (66) and for the conjugate reduction and alkylation of a,P-unsaturated ketones (67). 

Stereoselective reduction of ketones to alcohols by means of boiohydncle reagents (U S-BU3BH or t-BuCIBR (or lormation ol chiral alcohols)... 

Carballeira, J.D., Alvarez, E., Campillo,M,etal. (2004)DiplogelasinosporagrovesiilNll 171018, anew whole cell biocatalyst for the stereoselective reduction of ketones. Tetrahedron Asymmetry, 15 (6), 951-962. 

LaRonde, F.J., Brook, M.A. Stereoselective Reduction of Ketones Using Extracoordinate Silicon Cj-Symmetric Ligands, Inorganica Chim. Acta. 

Stereoselective reduction of ketones. This hydride (1) reduces f-butylcyclo-hexanone to about equal amounts of the corresponding axial and equatorial alcohols. Trost et al.2 used 1 to reduce the 3-keto group of 2 to the 3a-alcohol. Other methods were less selective. 

Stereoselective reduction of ketones.1 The germine triester 2 is reduced by 1 in HOAc to the 73-alcohol (3) in 92% yield. In contrast, reduction with NaBH4 gives the 7a-alcohol as the major product. The difference in stereoselectivity is attributed to the a-C14-hydroxy group. 

Highly diastereoselective reduction of ketones.3 The stereoselective reduction of ketones has been previously reported using chirally modified hydride... 

Stereoselective reduction of ketones. This borohydride (1) is comparable to lithium tri-.ver-butylborohydride (4. 312-313) for stereoselective reduction of cyclic ketones to the less stable alcohols, but less stereoselective than lithium trisiamylborohydride (7, 216-217). The by-product formed in reductions with I can be removed as an insoluble ate complex formed by addition of water, simplifying isolation of the reduction product. 

Enantioselective Ketone Reduction. After the pioneering work of Itsuno et al., Corey s group isolated the 1,3,2-oxazaborolidine derived from chiral a,a-diphenyl-2-pyrrolidinemethanol (2) and applied it (and also other related B-alkyl compounds) to the stereoselective reduction of ketones with borane-tetrahydrofuran, borane-dimethyl sulfide (BMS) or catecholborane.It was named the CBS method (after Corey, Bakshi, and Shibata). Since then, the CBS method has become a standard and has been extensively used, specially for aromatic and a,p-unsaturated ketones, not only in academic laboratories but also in industrial processes. ... 

Coenzyme NAD(P)+ involves a nicotinamide derivative and the transfer of a hydrogen species in a stereoselective manner via a 1,4-dihydropyridine (47 Scheme 10) and has led to much work on the reduction of NAD and its simpler derivatives (46 R = PhCH2, C12H25). Most work has been done on the stereoselective reduction of ketones, but heteroaromatic cations have also been reduced (see Section 3.6.2.3). Both single-electron transfer (SET) and direct hydride transfer mechanisms have been pro-posed.2°... 

Stereoselective reduction of ketones.2 Corey s synthesis of prostaglandins utilizes as a key intermediate the enone (1). One major synthetic problem is the stereoselective reduction of the carbonyl group to the desired 15S alcohol (Ila). Reduction with various borohydride reagents or various trialkylborohydrides (R, R2R3BH Li+) affords about... 

Use Stereoselective reduction of ketones conjugate reduction and alkylation of a,(3-unsaturated ketones. 

Use Reagent for the stereoselective reduction of ketones. Has been used in prostaglandin synthesis. 

In Sequence 3, one of the necessary inversions was effected by a highly stereoselective reduction of ketone 62 with the hindered reagent lithium perhydro-9B-boraphenalylhydride to obtain alcohol 63. Conversion of the terminal epoxide 64a to the desired cw-(5/ )-55 was unexpectedly difficult, as compared with the corresponding reaction in Sequence 1. The difficulty was ascribed to steric... 

One of the most widely used supported reagents for reduction is polymer-supported borohydride. An interesting example is the final step of the total synthesis of polysphorin 55, an anti-malarial natural product (Scheme 4.15) [62]. The stereoselective reduction of ketone 54 occurred with excellent diastereomeric excess when PS-BEMP was used, affording the 55 in 90% yield. 

Stereoselective reduction of ketones. The Luche reagent is useful for selective reduction of ketones in the presence of aldehydes, and for selective reduction of enones and enals to alcohols. The reagent can also invert the selectivity of hydride reduction of cyclic ketones such as la. Reduction of la with a metal boron and aluminum hydrides. 

Reduction of aldehydes and ketones is possible with borane. Stereoselective reduction of ketones is possible when a heteroatom is located a- or p- to the carbonyl group. Treatment of a (3-hydroxy-ketone with catecholborane results in the selective formation of the syn 1,3-diol product (7.94). The borane reacts preferentially with the alcohol to release hydrogen gas and to form the boronic ester 107. A second equivalent of the borane then effects the reduction to give the syn diastereomer. For the preparation of the anti diastereomer, triacetoxyborohydride can be used (see Scheme 7.86). 

In a totally different approach, Noyori et al. have used binaphthol-modifled aluminum hydride reagent for enatioselective reduction of alkynyl ketones. Suitably modified boranes can be used for stereoselective reduction of ketones. Along these same lines. Midland" has developed Alpine borane (1, Scheme 21.5), which is excellent for several acetylenic ketones but has been found inefficient for hindered ot,p-acetylenic ketones. To overcome this problem, Brown et al." have introduced P-chlorodiisopinocamphenyl borane 2(-)-DIP-Cl (2, (Scheme 21.5), which reacts well with hindered ketones to provide the corresponding propargyl alcohols in 96 to 99% e.e. 

Synthetic highlights A variety of pathways have been taken in the synthetic approach to sertraline. These include stereoselective reduction of ketones and imines under kinetic and thermodynamic control, using diastereoselective or enan-tioselective catalysts and reagents, desymmetrization of oxabenzonorbomadiene followed by the Suzuki coupling of arylboronic acids and vinyl halides and Pd-Catayzed (Tsuji-Trost) coupling of arylboronic acids and allylic esters. For the production of sertraline, the simulated moving bed (SMB), a cost-effective technology, has been introduced. 

Stereoselective Reduction of Ketones and Imines Under Kinetic... 

Lavandera, I Kern, A Schaffenberger, M., Gross, J., Glieder, A de Wildeman, S., and Kroutil, W. (2008) An exceptionally DMSO-tolerant alcohol dehydrogenase for the stereoselective reduction of ketones, ChemSusChem, 1,431-436,... 

Optically active secondary alcohols have been prepared by the highly stereoselective reduction of ketone complexes or by the addition of Grignard reagents to substituted benzaldehyde complexes (Meyer and Dabard, 1972). The complexed benzaldehydes (LXXIV) and aromatic ketones (LXXV) are obtained from the corresponding acids (Meyer, 1973). Reduction of the ketones (LXXV) with KBH4 or reaction of the benzaldehyde complex (LXXIV) with the appropriate Grignard reagent leads to the same diastereo-... 

Stereoselective reduction of ketones to form chiral alcohols is one of the most useful reactions in organic synthesis [1]. Chiral alcohol stmctures are frequently embodied in pharmaceuticals and other high-value compounds, and reduction of the corresponding ketone is often the most practical route available. As a result, methods for stereoselective ketone reduction that are broadly useful and applicable to a wide range of compounds have been widely sought, and significant effort has been made to the development of methods that produce alcohols with high enantiomeric purities [1],... 

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