Enantiotopic group

This point is also strikingly demonstrated in the enantiotopic group and diastereofacial selective allylboration of the me so complex 5 that provides the (45,65)-diastereomer with 45 1 diastereoselectivity and >98%ee85b. 

Polypropionate chains with alternating methyl and hydroxy substituents are structural elements of many natural products with a broad spectrum of biological activities (e.g. antibiotic, antitumor). The anti-anti stereotriad is symmetric but is the most elusive one. Harada and Oku described the synthesis and the chemical desymmetrization of meso-polypropionates [152]. More recently, the problem of enantiotopic group differentiation was solved by enzymatic transesterification. The synthesis of the acid moiety of the marine polypropionate dolabriferol (Figure 6.58a) and the elaboration of the C(19)-C(27) segment of the antibiotic rifamycin S (Figure 6.58b) involved desymmetrization of meso-polypropionates [153,154]. 

A different MS-based ee-assay makes use of a proline-derived mass-tagged acylating agent.95 In the course of derivatization it is necessary that some degree of kinetic resolution comes about. The sensitivity of the method was reported to be 10% ee. It can also be applied to the reaction of a prochiral compound lacking enantiotopic groups, as in the transformation of acetophenone to phenylethanol. 

Schreiber et al.47 have described a mathematical model that combines enantiotopic group and diastereotopic face selectivity. They applied the model to a class of examples of epoxidation using several divinyl carbinols as substrates to predict the asymmetric formation of products with enhanced ee (Scheme 4-28). 

Enzyme-catalyzed reactions can provide a rich source of chiral starting materials for organic synthesis.2 Enzymes are capable of differentiating the enantiotopic groups of prochiral and mew-compounds. The theoretical conversion for enzymatic desymmetrization of mew-compounds is 100% therefore enzymatic desymmetrization of mew-compounds has gained much attention and constitutes an effective entry to the synthesis of enantiomerically pure compounds. 

As mentioned in Sect. IV-B, enantiotopic groups even in achiral substances may show nonequivalence. For example, this property sometimes can be used to distinguish meso compounds from their chiral isomers. Thus in the presence of TFPE, the meso isomer of dimethyl 2,3-diaminosuccinate (46) shows two equally intense methoxy singlets and an AB quartet for the now diastereotopic methine hydrogens (88). This coupling clearly shows 46 to be the... 

Reetz and coworkers developed a highly efficient method for screening of enantioselectivity of asymmetrically catalyzed reactions of chiral or prochiral substrates using ESI-MS [60]. This method is based on the use of isotopically labeled substrates in the form of pseudo-enantiomers or pseudo-prochiral compounds. Pseudo-enantiomers are chiral compounds which are characterized by different absolute configurations and one of them is isotopically labeled. With these labeled compounds two different stereochemical processes are possible. The first is a kinetic separation of a racemic mixture, the second the asymmetric conversion of prochiral substrates with enantiotopic groups. The conversion can be monitored by measuring the relative amounts of substrates or products by electrospray mass spectrometry. Since only small amounts of sample are required for this method, reactions are easily carried out in microtiter plates. The combination of MS and the use of pseudo-enantiomers can be used for the investigation of different kinds of asymmetric conversion as shown in Fig. 3 [60]. 

Enantiotopic group differentiating reactions54 include the following 5 examples. 

Enantiotopic functional group differentiation is the domain of enzymes, whose use for such purposes is now well established as a method of broad applicability. This topic has been reviewed extensively 84 90-90a. The utility of nonenzymatic methods to achieve enantiotopic group differentiation is less well established. This topic has also been reviewed3. Diastereotopic group differentiation thus far involves substrates with chiral amide groups. 

A different approach to enantiotopic group differentiation in bicyclic anhydrides consists of their two-step conversion, first with (/ )-2-amino-2-phcnylethanol to chiral imides 3, then by diastereoselective reduction with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) to the corresponding chiral hydroxy lactames 4, which may be converted to the corresponding lactones 5 via reduction with sodium borohydride and cyclization of the hydroxyalkyl amides 101 The overall yield is good and the enantioselectivity ranges from moderate to good. Absolute configurations of the lactones are based on chemical correlation. 

Enantiotopic Groups The same in all scalar properties, distinguishable only under chiral conditions. 

Constitutionally Heterotopic and Diastereotopic Groups Differ in all scalar properties and are distinguishable under any conditions, chiral or achiral. Asymmetric molecules cannot contain homotopic or enantiotopic groups, only diastereotopic or constitutionally heterotopic groups. 

Many instances of stereospecific selection of enantiotopic groups or faces may be found in nature. One such is extracted from the tricarboxylic acid cycle and is shown in Exercise 1.6. At each step, achiral reactants are transformed to achiral products with high stereospecificity ... 

Nuclear magnetic resonance chemical shift differences can serve as an indicator of molecular symmetry. If two groups have the same chemical shift, they are isochronous. Isochrony is a property of homotopic groups and of enantiotopic groups under achiral conditions. Diastereotopic or constitutionally heterotopic groups will have different chemical shifts (be anisochronous), except by accidental equivalence and/or lack of sufficient resolution. 

Enantiotopic groups are isochronous in achiral solvents and distinguishable (anisochronous) in chiral solvents. 

Figure 1.6. Effect of solvent and solute optical purity on the appearance of NMR signals of enantiomers or enantiotopic groups (bottom row).

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