Simple Guidelines for Reaction Stereochemistry

Stereochemical consequences of reacting three different types of carbonyls with a hydride reducing agent. 

As we can anticipate the stereochemical relationships among the products, we can also evaluate the symmetry properties of the transition states of the hydride addition reactions. For acetone, there is only one possible transition state and only one product. For 2-butanone, the transition states derived from top and bottom attack are enantiomeric. As such they will have equal energies, and so AG will be the same for the formation of the two enantiomeric products. As a result, a racemic mixture must form. Finally, in the reduction of (R)-3-chloro-2-butanone, the two transition states are diastereomeric, and so they are expected to have different energies (diastereomers differ in all ways). Since the starting point for the two reactions is the same, AG is expected to be different for the two, and therefore the rates for formation of the two diastereomeric products cannot be the same. Since the rates of formation of the two products are not the same, we can state with certainty that the reduction of (R)-3-chloro-2-butanone is expected to not produce a 50 50 mixture of the two products in the initial reaction. This can be anticipated from first principles. When we start from a single reactant and produce two diastereomeric products, we do not expect to get exactly a 50 50 mixture of products. However, as is always true of a symmetry argument, we cannot anticipate how large the deviation from 50 50 will be—it may be 50.1 49.9 or 90 10. We can only say that it is not 50 50. 

Homotopic groups cannot be differentiated by chiral reagents. 

Diastereotopic groups are differentiated by achiral and chiral reagents. 

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