Prelog s rule

It is always advisable to examine the complete molecular topology in the neighborhood of the chiral carbon atom and to confirm the results by employing another analytical method before the final assignment. In conclusion, Prelog s rule does predict the steric course of an asymmetric synthesis carried out with a chiral a-keto ester, and the predictions have been found to be correct in most cases. Indeed, this method has been widely used for determining the absolute configuration of secondary alcohols. 

Hydroxy esters have been obtained successfully with baker s yeast (Sac-charomyces cerevisidae), and this has shown a wide scope of application. The facial selectivity in the reduction of both isolated ketones and //-keto esters can be reliably determined by using Prelog s rule,8 which predicts that the hydrogen addition by the yeast will occur from the front face (Scheme 8-2). Anti-Prelog microbial reduction of a-ketones with Geotrichum sp. 38 (G38) has been introduced by Gu et al.9... 

Figure 2.23 Enantioselective reduction of unsymmetricaUy substituted ketones by dehydrogenases yields secondary alcohols. The reaction may either follow Prelog s rule (addition of hydride from re-side) or they may not (anti-Prelog).

However, it should be noted that caution should be exercised when Prelog s rule is applied to such complicated systems as intact cells (baker s yeast), which may contain oxidoreductases of different stereoselectivity230 231. For example, in the reduction of 39 to alcohol 40, Prelog s rule fails232. 

A rule, similar to Prelog s rule, has been proposed for the enzyme-mediated hydrolysis of the esters of secondary alcohols. Esters of the enantiomers 31 usually react faster. This rule correctly predicted the configuration of 14 out of 15 substrates when cholesterol esterase was used, 63 out of 64 substrates with a lipase from Pseudomonas cepacia, and of 51 out of 55 cyclic substrates using a lipase from Candida rugosa24°. 

A hypothetical doubly-bridged allene 123 of D2 symmetry was first formulated in Cahn, Ingold, and Prelog s classical paper 11 > in which they summarized their novel proposal for specifying various molecular chiralities. Despite the close structural resemblance between 123 and [m.m]betweenanene, Cahn, Ingold and Prelog s rules shows that the chirality of these two classes of compounds are to be specified as axial and planar respectively. 

Asymmetric synthesis in aldol-type reaction involving magnesium ester or lactone enolates has also been reported. Enolate of (—)-menthyl or (-l-)-bornyl acetate reacts with substituted benzophenones or a-naphtophenones to yield, upon hydrolysis of the resulting esters, optically active /3-hydroxyacids. Although these results are interpreted in terms of a steric factor. Prelog s rules are not applicable to these reactions (equation 88). 

The most representative results of these additive systems are (1) allyl alcohol seems to inhibit the Si-face attack of the hydride, and (2) allyl bromide inhibits the. Re-face attack. In this system, if it is assumed that CF3 is sterically less demanding than the CH2COCH3 substituent, Prelog s rule holds for the yeast-allyl bromide additive reduction system, whereas it is not followed when the additive is allyl alcohol [26]. 

A potentially useful extension of the Cram s rule is the asymmetric induction provided by a remote ester (Prelog s rule). ... 

Using isolated enzymes instead of whole cells, similar problems are to be considered only in a few cases. ADH from Thermoanaerobium brockii shows varying enantiomeric excess of the product depending on the structure of the ketone to be reduced. Conversions with this enzyme yield in products with low (20% for the reduction of acetophenone) or high ee value (100% for the reduction of p-Cl-acetophenone). Predictions about the stereospecificity of HLADH catalyzed reductions can be made for simple acyclic substrates applying Prelog s rule [37] and for more complex compounds using the cubic-space model developed by Jones and Jakovac [38],... 

Carbonyl Group Reductions. Early applications of BY date back to the end of the 19th century and the first examples are reductions of carbonyl compounds. The widespread applications of this biotransformation are based on some systematic investigations on various ketones and the stereochemical outcome of the reaction is generally described by the so-called Prelog s rule which successfully applies to a great number of structures (eq 1). 

Table lists the results of the additions of both chiral and achiral alkoxytrialkylaluminates (20) to chiral a-keto esters (21). Some trends arc readily tqiparent (i) sodium is a superior cation as compared to lithium and potassium (entries 11-14) (ii) the configuration of the chiral moiety of the ester substrate dictates the facial preference (entries 1-7) and the preference follows the dictates of Prelog s rule (iii) there is an observable solvent effect with a preference for hexane/ether mixtures (iv) either (+)- or ( )-(2S,3/ )-4-dimethylamino-l,2-diphenyl-3-methyl-2-butanol (Darvon alcohol or (Zhirald) is the best of the... 

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