Borohydrides asymmetric reduction

J -Dehydroquinolizidine reacts with the enantiomeric (—)- and (-l-)-menthyl chloroformates forming (—)- and (-l-)-menthoxycarbonyl- -dehydroquinolizidines. These can be reduced as such or in the form of their immonium salts with sodium borohydride to (—)- and (+)-l-menthoxy-carbonylquinolizidines, which give (+)- and (-)-lupinin, respectively, on reduction with lithium aluminum hydride (243). The optical yield of the asymmetric reduction is about 10%. 

Most of the attempted asymmetric reductions have used sodium borohydride in conjunction with quaternary ammonium catalysts. Recently, the solution structures of ion pairs formed by quaternary ammonium ions derived from quinine with borohydride ion have been characterized by nuclear magnetic resonance methods in CDC13.1741... 

Asymmetric reduction of dialkyl ketones. The borohydride 1 reduces dialkyl ketones with low enantioselectivity. However, treatment of the lithium dihydri-doborate 2 with methanesulfonic acid provides Reagent I, which consists of 1 equiv. of R,R-1 and 0.2 equiv. of 2,5-dimethylborolanyl mesylate, which serves as a... 

Asymmetric reduction of a-keto esters The chromium-complexed a-keto ester 1 is reduced to the carbinol by sodium borohydride with surprisingly high... 

Asymmetric reduction of -arylcarbonyl esters.1 Reduction of these esters with lithium borohydride and (R,R )-1 and t-butyl alcohol affords the corresponding 3-hydroxy esters in 80-92% ee (equation I). 

Isosorbide (3) and isomannide (4) act as chiral auxiliaries for the sodium borohydride reduction of some prochiral ketones optical yields of up to 20% were achieved. It seems that the isohexides form chiral complexes with sodium borohydride, whereby the chiral information is transferred to the substrate.219 Optical active alcohols were obtained by reduction of appropriate ketones with sodium or lithium borohydride in the presence of isosor-bide.219 Asymmetric reduction of propiophenone using sodium borohydride, modified with (+)-camphoric acid and isosorbide, resulted in C -phenylethylcarbinol in 35% enantiomeric excess.2,9b... 

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

A combination of chiral cobalt-catalyst and sodium borohydride was successfully applied to the asymmetric reduction of aromatic ketones. A chiral cobalt complex 164 (5 mol%), prepared from the corresponding salen-type chiral bisketoaldimine and cobalt(II) chloride, catalyzed the reduction of dimethylchromanone 165 in the presence of sodium borohydride (1.5 equiv to ketone) in chloroform, including a small amount of ethanol at -20°C for 120 h to give alcohol 166 92% ee (S ) in 94% yield (Scheme 2.18) [94], Addition of tetrahydrofurfuryl alcohol (THFFA) to the reaction system or the use of pre-modified borohydride, NaBH2(THFFA)2, improved the catalyst activity, that is, using this protocol, the reactions of ketone 165 and... 

A review describing the major advances in the field of asymmetric reduction of achiral ketones using borohydrides, exemplified by oxazaborolidines and /9-chlorodiisopino- camphenylborane, has appeared. Use of sodium borohydride in combination with chiral Lewis acids has been discussed.298 The usefulness of sodium triacetoxyboro-hydride in the reductive amination of aldehydes and ketones has been reviewed. The wide scope of the reagent, its diverse and numerous applications, and high tolerance for many functional groups have been discussed.299 The preparation, properties, and synthetic application of lithium aminoborohydrides (LABs) have been reviewed. 

The boron atom dominates the reactivity of the boracyclic compounds because of its inherent Lewis acidity. Consequently, there have been very few reports on the reactivity of substituents attached to the ring carbon atoms in the five-membered boronated cyclic systems. Singaram and co-workers developed a novel catalyst 31 based on dicarboxylic acid derivative of 1,3,2-dioxaborolane for the asymmetric reduction of prochiral ketones 32. This catalyst reduces a wide variety of ketones enantioselectively in the presence of a co-reductant such as LiBH4. The mechanism involves the coordination of ketone 32 with the chiral boronate 31 and the conjugation of borohydride with carboxylic acid to furnish the chiral borohydride complex 34. Subsequent transfer of hydride from the least hindered face of the ketone yields the corresponding alcohol 35 in high ee (Scheme 3) <20060PD949>. 

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. 

Preparative Methods both enantiomers of the a-methyl sultam may be prepared on a multigram scale in optically pure form by asymmetric hydrogenation of imine (2a) followed by simple crystallization (eq 1). The (7 )-enantiomer of the a-f-butyl sultam may also be prepared in enantiomerically pure form by asymmetric reduction of imine (2b) followed by fractional crystallization. However, multigram quantities of either enantiomer of the a-t-butyl sultam may be prepared by derivati-zation of the racemic auxiliary (obtained in 98% yield from reaction of (2b) with Sodium Borohydride in MeOH) with 10-Camphorsulfonyl Chloride, separation of the resulting diastere-omers by fractional crystallization, and acidolysis. Prochi-ral imines (2a) and (2b) are readily prepared from inexpensive Saccharine by treatment with Methyllithium (73%) and t-Butyllithium (66%), respectively. 

Reduction of C=0 and C=N Bonds. Asymmetric reductions of prochiral ketones (19) to the corresponding chiral alcohols (20) using (S)-proline-modified borohydride reagents as the reductant have been published. The borane reductions of ketones (19) employing (S)-proline as chiral mediator proceeds with enantiomeric... 

Asymmetric Reduction of Ketones. Alkyl phenyl ketones can be asymmetrically reduced to the corresponding alcohol using Sodium Borohydride under phase-transfer conditions in the presence of a catalytic amount of QUIBEC (eq 13). The results indicate that the asymmetric reduction is due to the rigidity of the catalyst as well as the (3-position of the hydroxyl group on the quinine molecule. The asymmetric induction is much lower with a y-hydroxyl group. ... 

In 1951 Bothner-By first attempted asymmetric reductions based on the conversion of lithium aluminum hydride (LAH) into a chiral alkoxy derivative by reaction with (+)-camphor. Since this pioneering work, the use of chirally modified LAH reagents has been the focus of much attention. In 1979, the first virtually complete enantiofacial recognition of prochiral carbonyl compounds was accomplished by using LAH modified with optically pure 2,2 -dihydroxy-1,1 -binaphthyl and a simple alcohol (BINAL-H). Asymmetric reduction with chiral 2,5-dimethylborolane also gave alcohols in high optical yields." Recently, excellent results have been obtained using a chirally modified sodium borohydride... 

When borohydride reductions are carried out in the presence of either a chiral phase transfer catalyst or a chiral crown ether, asymmetric reduction of ketones occurs but optical yields are low. In the reduction of acetophenone with NaBH4 aided with a phase transfer catalyst (57), 10% ee was obtained. Similarly, reduction of acetophenone with NaBH4 in the presence of the chiral crown ether (58) was ineffective (6% ee)J Sodium borohydride reduction of aryl alkyl ketones in the presence of a protein, bovine semm albumin, in 0.01 M borax buffer at pH 9.2 affords (R)-carbinols in maximum 78% cc. ... 

RCH=CHCHOHR RCH=CHCOR 3.2.9 3.2.3 (asymmetric reductions) LAH-EtjOtAIHg DIBAH DlBAH-rvBuLi LiAi(OMe)3H Red-Al in benzene NaCNBH3-ZnCl2 BHj MegS 9-BBN NaBH<-CeCl3-M60H (i-PrO)2TiBH Li amino-borohydrides Zn(BH )2... 

Since the first asymmetric reduction of ketones with chiral borohydrides by Itsuno et al. [ 1 ], a number of studies on the asymmetric reduction of ketones with chiral borane reagents have been demonstrated [2]. Corey s oxazaborolidines are some of the most successful reagents [3 ]. The effect of fluorine substituents was examined in the asymmetric reduction of acetophenone with LiBH4 by the use of chiral boronates (73) obtained from substituted phenyl boronic acid and tartaric acid [4]. Likewise, 3-nitro, fluorine, and trifluoromethyl groups on the 3- or 4-position provided enhanced stereoselection (Scheme 5.20). 

Asymmetric reduction of prostereogenic cyclic imines with chiral sodium acyloxyborohy-drides, which arc easily prepared by the reaction of sodium borohydride with various A-acyl-a-amino acids, has been investigated. Triacyloxyborohydrides, derived from sodium borohydride (1 equiv) and (S)-TV-acylproline (3 equiv), were found to reduce 3,4-dihydropapaverine (2) to (5 )-norlaudanosine (3)30. 

By resolution of the benzyltetrahydroisoquinoline or preferably asymmetric reduction with a chiral borohydride of the precursor the chiral members of the series should be accessible bearing in mind the the efficient transformations already acomplished (ref. 167). In the light of potential shortages (ref. 186) and avoidance of dependence upon the sole natural commercial sourse, this synthetic strategy represents a practical approach to the medical opiates. 

Asymmetric reduction of ketones. This borohydride reduces even hindered ketones and with high stereoselectivity, as noted with other hindered trialkyl-borohydrides. Thus 2-methylcyclohexanone is reduced to c/y-2-methylcyclohexa-nol (99% isomeric purity). Of even greater interest, the alcohols formed on reduction are consistently enriched in the (R)-enantiomer to the extent of 10-40%. ... 

Asymmetric borohydride reduction. Colonna and Fornasier have examined the reduction of ketones with sodium borohydride under phase-transfer conditions in the presence of optically active ammonium salts containing at least one hydroxyl group. Of the seven catalysts tested (-)-benzylquininium chloride (1) (7, 311) was the most effective for asymmetric reduction of r-butyl phenyl ketone (pivalo-phenone) to the corresponding carbinol with optical yields as high as 32%. Two factors would appear to be important for this asymmetric reduction the catalyst must be conformationally rigid and the hydroxyl group must be in the 8-position to the onium function. ... 

The approach using cyclodextrin as a binding site has also been developed. Cyclodextrins are widely utilized in biomimetic chemistry as simple models for an enzyme because they have the ability to form inclusion complexes with a variety of molecules and because they have catalytic activity toward some reactions. Kojima et al. (1980, 1981) reported the acceleration in the reduction of ninhydrin and some dyes by a 1,4-dihydronicotinamide attached to 3 Cyclodextrin. Saturation kinetics similar to enzymatic reactions were observed here, which indicates that the reduction proceeds through a complex. Since the cavity of the cyclodextrin molecule has a chiral environment due to the asymmetry of D-glucose units, these chiralities are expected to be effective for the induction of asymmetry into the substrate. Asymmetric reduction with NAD(P)H models of this type, however, has not been reported. Asymmetric reduction by a 1,4-dihydronicotinamide derivative took place in an aqueous solution of cyclodextrin (Baba et al. 1978), although the optical yield from the reduction was quite low. Trifluoromethyl aryl ketones were reduced by PNAH in 1.1 to 5.8 % e.e. in the presence of 3-cyclodextrin. Sodium borohydride works as well (Table 18). In addition to cyclodextrin, Baba et al. also found that the asymmetric reductions can be accomplished in the presence of bovine serum albumin (BSA) which is a carrier protein in plasma. 

Table 18. Asymmetric reduction of aryl trifluoromethyl ketones with PNAH and sodium borohydride.

Table 19. Asymmetric reduction of carbonyl compounds with sodium borohydride in the presence of BSA.

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