Ketones resolving agents

Resolving Agent. Scalemic CSA has been used to resolve amines by forming diastereomeric salts which can be separated by fractional crystallization (eq 11). In this instance, after obtaining the desired crystalline diastereomeric salt, the undesired diastereomer was completely transformed into the desired one by a resolution-racemization procedure (eq 12). Additionally, racemic ketones can be resolved by forming enantiomeric iminium salts (eq 13). Two different procedures have been devised depending on the ease of enamine formation. 

Chromatography of radiochemically homogeneous terpenoids has been reviewed useful gas-chromatographic techniques reported include the use of polyphenyl ether in g.c.-m.s. of 23 monoterpenoid hydrocarbons,the use of 3,4,5-trimethoxybenzylhydrazine for pre-column removal of aldehydes and ketones, and the resolution of some bicyclic alcohols and ketones by co-injection with a volatile chiral resolving agent. 

USE The racemic form as reagent for the characterization of aldehydes and ketones. The optically active forms as resolving agents for carbonyl compds possessing asymmetric carbon atoms. 

Some commonly used resolving agents are summarized in Table 1 [15-48]. The formation of non-covalent diastereomeric salts is driven by ionic interactions. Therefore, suitable functional groups (acidic or basic) are required to be present in both counterparts. This makes impossible a direct application of the diastereomeric crystallization technique to several classes of chiral compounds such as alcohols, aldehydes, ketones, diols, thiols, dithiols, and phenols. This is a critical disadvantage of this technique. The compounds of the above-mentioned groups may be transformed to their more polar derivatives and resolved as such. However, this requires an additional reaction step, and reagents, and the recovery of the starting material after the resolution may not always be easy. 

Resolution of compounds containing functional groups that are not acidic or basic requires a reversible functional group interconversion involving a chiral resolving agent. For example, the reaction of a racemic alcohol with a chiral carboxylic acid results in a mixture of diastereomeric esters that can be separated. After separation, hydrolysis of the ester regenerates the desired alcohol. To resolve a racemic ketone or aldehyde, a reaction with a chiral diol or a chiral amine could be employed to form diastereomeric acetals or imines, respectively. 

Synthetic. Resolving agent for aldehydes and ketones. Shows about 5 the pharmacol. activity of (— )-ephedrine. Mp 40-40.5°. 

Many esterases and lipases are now commercially available and widely used in the synthesis of bioactive compounds [47]. Thanks to the rather broad substrate specificity of lipases, they are employed as resolving agents in various different cases. The enantiomers of 3 were prepared by asymmetric hydrolysis of ( )-19 with PLE as shown in Fig. 11 [10]. Their pure 3,5-dinitrobenzoates 20 could be obtained by recrystallization, hydrolysis of which furnished the pure enantiomers of 3. Optically active 3 is also obtainable by chemical asymmetric reduction [11] or by asymmetric hydrogenation [22] of the corresponding ketone. The enzymatic method is simpler than other methods, especially when both the enantiomers of 3 are required. As already shown in Fig. 3, 3 could be converted to various natural products. 

A similar microwave-assisted cyclization in the presence of ammonium acetate of an a-ketoamide, obtained by acylation of an a-aminoketone, was recently described for the synthesis of the antifungal agent Nortopsedin D [46]. The problem of the instabiUty of the a-amino ketones was successfully resolved by in situ acylation of the amine derived from Staudinger reaction of the azide 50 with a phosphine (Scheme 16). This ketoamide was... 

Racemic N-methylimines derived from 4-substituted 1-tetralones were ki-netically resolved by asymmetric hydrosilylation with phenylsilane (1 equivalent) as a reducing agent using the titanocene catalyst (R)-ll (substrate Ti= 100 1) at 13 °C, followed by a workup procedure to afford the corresponding chiral ketones and chiral cis amines with very high enantio- and diastere-oselectivity (Scheme 12) [28], The extent of the enantiomeric differentiation, kfast/kslow was calculated to be up to 114. The ris-selectivity of this reaction was... 

Whereas the chiral TEMPO analog 87 was used to resolve racemic secondary alcohols, the D-fructose-derived ketone 88 [137] proved useful for oxidative resolution of racemic diols (Table 10.13) [138, 139], Persulfate in the form of Oxone, Curox, etc., served as the final oxidizing agent, and the dioxirane generated from the ketone 88 is the chiral active species. Because of the relatively low conversions (except for unsubstituted dihydrobenzoin) at which the ee stated were achieved, the method currently seems to be of less practical value. Furthermore, typically 3 equiv. ketone 88 had to be employed [138, 139]. 

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