Enantiotopic halves

Synthesis of a chiral compormd from an achiral compound requires a prochiral substrate that is selectively transformed into one of the possible stereoisomers. Important prochiral substrates are, for example, alkenes with two different substituents at one of the two C-atoms forming the double bond. Electrophilic addition of a substitutent different from the three existing ones (the two different ones above and the double bond) creates a fourth different substituent and, thus, an asymmetric carbon atom. Another class of important prochiral substrates is carbonyl compounds, which form asymmetric compounds in nucleophilic addition reactions. As exemplified in Scheme 2.2.13, prochiral compounds are characterized by a plane of symmetry that divides the molecule into two enantiotopic halves that behave like mirror images. The side from which the fourth substituent is introduced determines which enantiomer is formed. In cases where the prochiral molecule already contains a center of chirality, the plane of symmetry in the prochiral molecules creates two diastereotopic halves. By introducing the additional substituent diasterom-ers are formed. 

In an achiral environment, both enantiotopic halves of the prochiral compound are even, which means the addition reaction in the case depicted in Scheme 2.2.13 would lead to a 1 1 mixture of the (R)- and (S)-enantiomers. Such a mixture is called a racemic mixture. 

In a chiral environment the two enantiotopic halves of a prochiral compound behave differently. Thus, the addition of a reactant proceeds in a selective mannet The higher the degree of differentiation between the two halves, the higher the selectivity. The chiral information necessary to create stereochemically uneven halves at the prochiral center is called chiral induction. Typical ways to introduce chiral induction into a system to realize stereoselective syntheses are ... 

As for any desymmetrization of meso compounds, enantioselectivity comes from the ability of a homochiral base to distinguish between two enantiotopic protons, in this particular case, to discriminate between the two pseudo-axial protons of the rapidly equilibrating enantiomeric half-chair conformations 51 and 52 (Scheme 25). 

We have drawn the product with stereochemistry even though it is not chiral. This is because one of the two enantiotopic thiol esters is hydrolysed while this intermediate is still bound to the enzyme, so a single enantiomer of the half-acid/half-thiol ester results. 

This also clearly shows that the enzyme distinguishes between the enantiotopic hydroxymethyl groups in glycerol transforming only the one residing in the Si half-space (see Chapter 1, Fig. 18). 

Heterotopic Either diastereotopic or enantiotopic. Refers to either the Re or Si half space of a two-dimensionally chiral triangle, as shown below [91,92]. See also Re, Si, enantiotopic, diastereotopic. 

When symmetrical 1,3,5-tri-0-benzoyl-myo-inositol 137, which is derived by benzoylation of myo-inositol in one step, reacts enantioselectively at the enantiotopic C-4 or -6 position with an optically active compound, the chiral inositol derivative can be obtained essentially without losing half of one of the enantiomers due to meso-compound. On the basis of this consideration, various chiral auxiliaries were examined and only tartaric acid monoesters 164 were found to be extraordinarily efficient (Scheme 4-1). 70 Thus, treatment of the benzoate 137 with isopropylidene or... 

In order to discuss facioselectivity concisely, cate needs to classify molecular faces (half-spaces). - In 1975, we categorized time-resolved/time-averaged planar stereotopic molecular faces into homotopic, enantiotopic, and diastereotopic classes." ... 

Despite the independent nature of these two attributes, stereotopicity and chirotopicity of intramolecular sites are intimately intertwined. When molecular half-spaces are considered in terms of these two attributes, one finds five types of molecular faces two that are homotopic -achirohomotopic (H,H) and chirohomotopic (H, H ), enantiotopic faces (E a), and two types of diastereotopic faces - achirodiastereotopic (D,F) and chirodiastereotopic (D, F ) (Figure 12.1)." Of these five t) es of molecular faces, types (H,H), (E, 3) and (D,F) are foimd only in achiral molecules, while (H, H ) and (D, F ) faces are found only in chiral molecules. 

An application of this approach is the synthesis of chiral primary alcohols labeled with tritium at one of the enantiotopic a-hydrogens. Liver alcohol dehydrogenase, for example, reduces benzaldehyde to (7 )-[methylene- H]benzyl alcohol (27) in the presence of NAD/NAD H, which is regenerated by oxidation of (/ ,5)-[l- Hi]ethanol to acetaldehyde. Because the enzyme transfers exclusively the Re-positioned isotope of (R,5)-[ 1 - Hj Jethanol, the theoretical radiochemical yield is only 50% (the other 50% remains in acetaldehyde), and the specific activity of the product is only half that of this isotope source. One way to overcome this drawback is to use achiral, secondary alcohols such as [1- H]-cyclohexanol or [l- H]cyclopentanol (2S) as isotope sources. The corresponding (5)-antipode of 27 would be accessible by analogous reduction of benz[ H]aldehyde using nonisotopic cofactors. 

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