Use of Carbohydrates in Asymmetric Synthesis

The essence of asymmetric synthesis is the creation of asymmetric centers under the influence of other asymmetric centers in such a way that the resulting enantiomers or diastereoisomers are formed in unequal proportions. Most reactions in asymmetric synthesis that have been described involve the conversion of trigonal carbon atoms into asymmetric, quadrivalent carbon atoms, and this article will be principally concerned with such reactions, although, in many instances, the principles involved may also be applied to asymmetric reactions in which, for example, chiral phosphorus or sulfur atoms are formed. In all reactions in which are formed mixtures of enantiomers having one enantiomer in preponderance, it is possible to describe the stereoselectivity of the reaction in terms of optical yield (optical purity, or enantiomeric yield). The precise significance of these terms has been described in detail elsewhere,1 but, practically, where at a selected wavelength, [a] is the specific rotation of the reaction product and [A] is the specific rotation of a pure enantiomer, the optical yield = [a]/[A]. Thus, the value of the optical yield is a measure of the excess of one enantiomer over the other. 

Type 2. Reactions in which new asymmetric centers are created in molecules that already possess one asymmetric center or more and in which the new asymmetric center may be liberated from the parent molecule by simple hydrolytic reactions. The most common reactions of this type are those to which the Prelog rule4 applies for example, the addition of methylmagnesium iodide to (—)-phenylpyruvate, followed by hydrolysis to give (—)-atrolactic acid. 

Type 3. Reactions in which new asymmetric centers are created immediately adjacent to existing asymmetric centers in molecules that contain one asymmetric center (or more). These are the reactions to which the Cram rules5 are usually considered to apply. The stereoselectivity of this type of reaction is usually higher than that normally found in reactions of Types 1 and 2. The synthetic utility of reactions of this type has suffered from the disadvantage that the new asymmetric center in non-carbohydrate compounds cannot usually be detached easily from the original asymmetric framework. However, the ready availability of glycosuloses has provided many examples of Cram-type reactions in carbohydrate chemistry, and the fact that the new asymmetric centers may be detached from the original carbohydrate framework has been exploited. 

In the following Sections will be given examples illustrating that, in the three types of reaction already listed, where carbohydrates have been used to provide the asymmetric environment, the optical yields obtained were in most instances significantly higher than when other chiral molecules were employed. 

Grignard Addition Reactions in Solvents containing Carbohydrate Derivatives [Type 1] 

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