Enantioselectivity catalytic reduction of ketone

Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

Highly Enantioselective Catalytic Reduction of Ketones Paying Particular Attention to Aliphatic Derivatives... 

Kadyrov, R., Seiko, R. Highly enantioselective catalytic reduction of ketones paying particular attention to aliphatic derivatives, in Organic Synthesis Highlights / /194-206 (VCH, Weinheim, New York, 2000). 

Use of Chiral Phosphine-Oxide in the Catalytic Enantioselective Borane Reduction of Ketones... 

As described in the catalytic enantioselective borane reduction of ketones using oxazaphospholidine-borane complexes, a mechanistic rationale has been proposed. Nevertheless, this mechanism cannot fully explain the enantioselec-tivity encountered. 

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. 

Catalytic Enantioselective Reduction of Ketones. An even more efficient approach to enantioselective reduction is to use a chiral catalyst. One of the most developed is the oxazaborolidine 18, which is derived from the amino acid proline.148 The enantiomer is also available. These catalysts are called the CBS-oxazaborolidines. 

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%... 

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],... 

Enantioselective borane reduction of prochiral ketones catalysed by chiral oxabor-olidines is of considerable synthetic utility, but the catalytic cycle has to compete with direct borane reduction of the ketone. Accordingly, precise kinetic data on the latter would help optimize conditions for the former. Such a study has been... 

A chiral p-keto iminato Co complex in the presence of tetrahydrofuryl alcohol (THFA) and ethanol (or methanol) results in high enantioselectivity in reduction of aromatic ketones using NaBH4 as a hydride source (Figure 1.29). The in situ generated NaBH2(OR)(OC2H5) (ROH = THFA) reduces the Co complex to form a true catalytic CoH species. 

The control of reactivity to achieve specific syntheses is one of the overarching goals of organic chemistry. In the decade since the publication of the third edition, major advances have been made in the development of efficient new methods, particularly catalytic processes, and in means for control of reaction stereochemistry. For example, the scope and efficiency of palladium- catalyzed cross coupling have been greatly improved by optimization of catalysts by ligand modification. Among the developments in stereocontrol are catalysts for enantioselective reduction of ketones, improved methods for control of the... 

Reactions using catecholborane proceed smoothly in toluene (Scheme 16) (40). The utility of catalytic hydroboration of ketones has been demonstrated by the efficient enantioselective synthesis of a series of biologically active compounds (41). Scheme 17 shows some compounds prepared by using this method. Enantioselective reduction of trichloro-methyl ketones is a general route to a-amino acids and a-hydroxy esters it also allows ready synthesis of a precursor to the carbonic anhy-drase inhibitor MK-0417 (42). 

Reaction of achiral and chiral bis(oxazolines) (BOX) with catecholborane (CATBH) provides boron-BOXate complexes that can be used as catalysts in the enantioselective reduction of ketones. It has been shown that asymmetric transfer of the hydride ion from the boron atom of CATBH to the prochiral carbonyl is the rate-determining step of the catalytic reaction.314... 

Menthol catalyses the enantioselective reduction of ketones by NaBH4 in diglyme proton- and auto-catalytic possibilities are investigated, and trialkyl borate species generated during the reaction may also play a role in catalysis.302... 

Only limited success has been reported in the reduction of ketimines due to the low electrophilicity of the imine carbon and the rapid equilibration between the (E)- and (Z)-isomers. However, high enantioselectivity was achieved in catalytic reduction of imines of keto esters (Equation (261))1125 and oximes of acetophenone (Equation (262))1089,1125-1131 cyclic ketones (Equation (263)),1127 and a ketone possessing a boryl group (Equation (264)).1128... 

In 1987, Corey and co-workers proved that highly enantioselective reduction of ketones could be achieved by using stoichiometric borane in the presence of catalytic amounts of the oxazaborolidine 28a11 (Scheme 4.3j). Compound 28a, synthesized by heating (S)-(-)-2-(diphenylhydroxymethyl)pyrrolidine at reflux in THF with 3 equivalents of BH3 THF, shows excellent catalytic activity for the asymmetric reduction of acetophenone and other ketones. The B -methylated analog 28b was later synthesized to improve the air and moisture sensitivity associated with 28a. The third analog, 28c, with a 2-naphthyl substituent on the oxazaborolidine ring, has proven to be the best to afford the alcohol 29 with superb levels of enantioselectivity. 

In 1993, Bolm reported that these reactions could be performed using catalytic quantities (10 mol%) of the chiral P-hydroxy sulfoximine.132 The enantiomeric purities of the product alcohols ranged from 52% (1-indanone) to 93% (PhCOCHjOSiRj). In many cases the enantiomeric purities were enhanced using sodium borohydride as reductant in the presence of chlorotrimethylsilane.133 These methods have been extended to the asymmetric reductions of imines.134 /V-SPh-substituted imines gave the highest enantioselectivities and these reductions proceeded in the same stereochemical sense as the reductions of ketones. 

Table 1 Catalytic Enantioselective Reduction of Ketones using Oxazaborolidine (5)-(6)...

The isolation and characterization of the reagent derived from the reaction of p-amino alcohols and borane accompanied the first report of a truly catalytic procedure for the enantioselective reduction of ketones. - A representative example is shown in Figure Based on H and NMR spec-... 

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