Sodium borohydride ketones, aryl

Compared with boranes, borohydrides are inexpensive and easy to handle. As early as 1978 Colonna and Fornasier reported that aryl alkyl ketones such as acetophenone can be reduced asymmetrically by sodium borohydride by use of an aqueous-organic two-phase system and chiral phase transfer catalysts [20], In this study, the best enantiomeric excess (32%) was achieved when pivalophenone (11) was reduced in the presence of 5 mol% benzylquininium chloride (12) (Scheme 11.4) [20]. Other chiral phase-transfer catalysts, for example ephedrinium salts, proved less effective. 

The quaternary salts of ketals of 4-pyridyl alkyl and aryl ketones undergo reduction with sodium borohydride to give the expected 1,2,3,6-tetrahydropyridines.47" Reduction of an analogous ketal of a quaternary salt of a 3-pyridyl ketone led to rupture of the ketal ring.476... 

Arenetellurolates, ethenetellurolates, and alkanetellurolates prepared by reduction of diorgano ditellurium compounds with sodium borohydride in ethanol, THF/ethanol, or DMSO add to acetylenes in regioselective and iran.y-stereoselcctive reactions to produce aryl ethenyl tellurium products either predominantly or exclusively as (Z)-isomers. The yields are almost always higher than 70%. In reactions with acetylenic aldehydes, ketones, carboxylic acids, and esters the arenetellurolate becomes bonded to the carbon atom in a [i-position to the carbonyl group. 

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. ... 

The addition of a catalytic amount of Cp2TiCl2 dramatically increases the yield of the hydroacylated ketone formed in the hydroacylation of 1-alkenes with heteroaromatic aldehydes by using Wilkinson s complex and 2-amino-3-picoline as co-catalysts.1264 Cp2TiCl2 catalyzes the reduction of aryl halides by sodium borohydride. The reaction scope and mechanism are solvent dependent.1265... 

In 1978, Colonna and coworkers first demonstrated that in the presence of cinchona-derived PTCs, alkyl aryl ketones can be reduced asymmetrically with the inexpensive and easily handled sodium borohydride under aqueous-organic biphasic conditions. However, the enantiomeric excess of the corresponding alcohols was very disappointing. The best ee obtained in their study was 32% when pivalophenone was reduced in the presence of 5 mol% of benzylquininium chloride 1 (Scheme 5.28) [34]. Variants of this procedure were tried later by several research groups, but in all cases the enantioselectivities were too low for synthetic applications [35]. 

These are stable compounds which do not polymerise or autoxidise. For the most part, pyrrole-aldehydes and -ketones are typical aryl-ketones, though less reactive - such ketones can be viewed as vinylogous amides. They can be reduced to alkyl-pyrroles by the Wolff-Kishner method, or by sodium borohydride via elimination from the initial alcoholic product (cf. 16.11). Treatment of acyl-l-phenylsulfonyl-pyrroles with f-butylamine-borane also effects conversion to the corresponding alkyl derivatives. ... 

Apart from sodium borohydride, which is frequently used in water or water-alcohol mixtures to reduce ketones or aldehydes selectively, water is rarely used as the solvent in reductions, because of incompatibility with most reducing agents. However, samarium iodide reduction of ketones, as well as alkyl and aryl iodides is accelerated in water [99]. Likewise, the a-deoxygenation of unprotected aldonolac-tones is efficient when the SmI2-tetrahydrofuran-water system is used [100],... 

The difference with ketones is that its carbonyl (C=0) moiety or functional group is usually between two groups (alkyl and/or aryl). The reagents used to convert a ketone to an alcohol is LiAlHi, (lithium aluminum hydride), or NaBHit (sodium borohydride) and both must be used in acidic conditions. The acids used are hydrochloric acid or acetic acid. 

L. R. Reddy, N. Bhanumathi, K. R. Rao, D5mamic kinetic asymmetric synthesis of j8-aminoalcohols from racemic epoxides in cyclodextrin complexes under solid state conditions, Chem. Commun., 2000, 2321-2322, M. A. Reddy, N. Bhanumathi, K. R. Rao, Asymmetric synthesis of 2-azido-l-arylethanols from azido aryl ketone-j3-cyclodextrin complexes and sodium borohydride in water, Chem. Commun., 2001, 1974-1975. 

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.

As shown in Table 18, trifluoromethyl aryl ketones were reduced in 22.3-46.6 % e.e. by PNAH and 15.6-38.8 % e.e. by sodium borohydride in 1.5-1.7 mM solution of BSA. The degree of asymmetric induction was rather high in comparison with those from the reactions with cyclodextrin, which suggests the possibility that such a simple protein as BSA can provide a chiral reaction field, as an enzyme does. As already mentioned some proteins have a similar (or sometimes greater) affinity toward a molecule in the ground state in comparison with an enzyme. The difference between these two proteins in different classes is the affinity toward a transition state. The enzyme has to bind the transition state more strongly than the ground state. 

High enantioselectivities are obtained using tartaric acid-derived boronate ester 31 in combination with lithium borohydride or sodium borohydride for asymmetric reduction of alkyl or aryl ketones. The chiral Lewis add is easUy prepared in one hour, and the resulting alcohols are obtained in enantiomeric excesses of 88-99% (Equation 46) [44]. 

Full details have appeared on the reduction of aryl alkyl ketones with reagents prepared from sodium borohydride, a carboxylic acid, and 1,2 5,6-di-O-isopropylidene-a-D-glucofuranose (DIPGF 12) cf. S, 157), best results are... 

Reductions can also be performed in water. Systems for reduction of ketones in water can be water-compatible sodium and lithium borohydrides, amino acid-based cationic surfactants to reduce aryl ketones [19], iridium hydrides used in transfer hydrogenations, such as [Cp Irm(bpy)H]+ (Cp — q5-C5Mes, bpy = 2,2 - bipyridine) [20], and IrHCI2(cod) 2 with a chiral diaminodiphosphine ligand to form secondary alcohols in high enantioselectivity and almost quantitative yield (Equation 4.12) [21]. 

The selective reduction of enones may be achieved by use of the correct catalyst. Thus reduction of enones by sodium hydride-sodium alkoxide mixtures with zinc(ii) chloride as catalyst gives 1,2- whereas nickel(ii) acetate gives 1,4-reduction. Similarly, use of cobalt(ii) or nickel(ii) chlorides yields only saturated ketones from the borohydride reduction of /3-alkyl- or /3-aryl-thio-enones. ... 

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