Carbonyl compounds enantiomeric reductions

The control of enantioselectivity in the reduction of carbonyl compounds provides an opportunity for obtaining the product alcohols in an enantiomerically enriched form. For transfer hydrogenation, such reactions have been dominated by the use of enantiomerically pure ruthenium complexes [33, 34], although Pfaltz and coworkers had shown by 1991 that high levels of enantioselectivity could be obtained using iridium(I) bis-oxazoline complexes [35]. 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

A variety of macrocycles with asymmetric centers have been reported, examples of which are shown in (57) to (66). Chiral discrimination has been observed in the study of thiolysis of activated ester bonds with tetracysteinyl[18]crown-6 (67), e.g. Gly-L-Phe reacts up to 80 times faster than Gly-D-Phe with this ligand.231 The chiral macrocyclic ligand (66) is also capable of enantiomeric discrimination, by assisting in the selective reduction of carbonyl compounds with high optical yields.232,233... 

Figure 3.27 shows reaction equations and the energy relationships of the hydroboration of enantiomerically pure a-pinene with 9-BBN. The reagent approaches only the side of the C=C double bond that lies opposite the isopropylidene bridge. The addition is thus completely diastereoselective. Moreover, the trialkylborane obtained is a pure enantiomer, since the starting material is a pure enantiomer. It is used as Alpine-Borane for the enantioselec-tive reduction of carbonyl compounds (Section 10.4). 

Tetradentate chiral proton donors have been used for the asymmetric protonation of samarium enolates formed by the Sml2 reduction of a-heteroatom-substituted carbonyl compounds. For example, Takeuchi examined the reduction of a-heterosubstituted cyclohexanone 12 using Sml2 and the BINOL-derived chiral proton source 13.41 Ketone 14 was obtained in good yield and high enantiomeric excess (Scheme 2.11). Coordination of the proton source to samarium is key to the success of the transformation.41... 

In general, the enantiomeric excess and the configuration of the optically active alcohols are strongly dependent on the structure of the starting carbonyl compound many examples of diastereo-selective reduction have also been reported. The reduction of an epoxy ketone is accompanied by a stereocontrolled epoxide hydrolytic opening to afford a racemic triol, diastereomerically pure (eq 4). ... 

The cobalt(I) cobalamin catalyzed reduction of a-methyl-a,P-unsaturated carbonyl compounds produces the corresponding saturated derivatives having an (5)-configuration at the a-carbon (Scheme 81) 424 highest enantiomeric excess (33%) is exhibited by the (Z)-configurated methyl ketone. The... 

The remarkable specificity of a monoclonal antibody has been used by Schultz and co-workers [71 ] to control the selective reduction of the carbonyl compound 54 with NaBHaCN (eq. (3)). The observed enantiomeric excess of 96 % (S)-55 cannot be obtained with conventional chemical methods. 

Sequential Heck reaction and hydrosilylation of carbonyl have been carried out with the Grubbs I catalyst. AUyUc alcohols can be S3mthesized via conjugated carbonyl compounds prepared from cross-metathesis in situ by reduction with j-Bu2AlH. An access to enantiomeric 2,3-dihydroxyalkanoic esters is based on cross-metathesis, dihydroxylation and methanolysis. ... 

With strains of Saccharomyces the (25,35)-isomer is produced predominantly, accompanied by some of the (2/J,3,S )-isomer. Similar to ft-keto esters, the formation of the undcsired isomer can be decreased by the addition of an a,/i-unsaturatcd carbonyl compound, e.g.. methyl vinyl ketone, or an allylic alcohol. These additives probably act as inhibitors for the enzyme which produces the (2/ ,35)-isomer202 203. More recently, the microbial reduction of a variety of simple 2,2-disubstituted cyclic 1,3-diketones of various ring size has been investigated204 205 206. In most cases one of the substituents in the 2-position is methyl. The configuration of the hydroxy group in the reduced product is always S, and the enantiomeric excess is often high (Table 7). 

That is, in order for the phenomenon to be observed, both reactants must show inherent diastereoface selectivity in their reactions with achiral partners. If one of the reactants shows no inherent diastereoface selectivity in its reactions with achiral reactants, then mutual kinetic resolution will not be observed regardless of the stereoselectivity of the other reactant. For an example, consider the case of an enzyme which mediates some reaction, say reduction of the carbonyl group. We can let the enzyme be A and assume that, because of its uniquely-evolved molecular structure, it shows very high inherent diastereoface selectivity (thus, it will reduce prochiral carbonyl compounds to chiral alcohols with very high enantiomeric excess). For B, let us take a chiral aldehyde that shows no inherent diastereoface selectivity in its... 

Steric Effects.—The consequences upon chemical reaction of non-bonded interactions between enantiomeric pairs of molecules have been discussed an antipodal interaction effect was observed in a reductive camphor dimerization and in a camphor reduction. The full paper on the correlation of the rates of chromic acid oxidation of secondary alcohols to ketones with the strain change in going from the alcohol to the carbonyl product has now appeared. It is concluded that the properties of the product are reflected in the transition state for the oxidation. High yields of hindered carbonyls are available from the corresponding alcohols by reaction with DMSO and trifluoroacetic anhydride (TFAA) indeed, the more hindered the alcohol, the higher the yield of carbonyl compound reported Since the DMSO-TFAA reaction occurs instantaneously at low temperatures (<—50°C), it is possible to oxidize alcohols that form stable sulphonium salts only at low temperature. Thus, ( )-isoborneol reacts at room temperature to give camphene, the product of solvolysis of the sulphonium salt the oxidation product, ( + )-camphor, was obtained by the addition of base at low temperature. 

Other Unsaturated Alcohols. An improved procedure that has been reported recently for the preparation and utilization of alkali-metal acetylides in liquid ammonia allows the ethynation of sensitive carbonyl compounds to be carried out, in good yield, to give propargylic alcohols. The reduction of ap-acetylenic ketones to (S propargyl alcohols of high enantiomeric purity can be performed with NB-Enantrane (27) [cf. (6) earlier], which is derived from nopol benzyl ether as a low-cost alternative to (—)-a-pinene. a-Allenic alcohols have been prepared by the new routes shown in Schemes... 

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