Diastereofacial Selectivity in Acyclic Systems

Diastereofacial selection in nucleophilic additions to acyclic aldehydes and ketones is of major importance in synthetic organic chemistry. The greater conformational freedom of acyclic systems makes predictions as to the stereochemical outcome of such reactions more difficult than when the carbonyl group is contained within a cyclic framework. 

We may distinguish between enantiotopic or diastereotopic faces in trigonal moieties ( C=0 and C=C ). The faces of prochiral moieties can be differentiated as the Re or Si face by applying R) or S) sequence rules to the three substituents in the plane as viewed from each face.  

The two faces of the carbonyl moiety in acetaldehyde or in butanone, for example, are enantiotopic and are designated as Re face if the priority of the substituents is in a 

The two 7t-faces of an aldehyde or of a ketone with at least one stereogenic center are diastereotopic. As a result, the Re and Si attack by an achiral nucleophile (i.e., L1A1H4, EtMgBr, PhLi) or an achiral enolate ion differ in energy, so unequal amounts of products are formed (A B 1). The ratio of products reflects the bias of the chiral substrate to undergo preferential addition on one diastereotopic face. 

When two of the reaction components are chiral (any combination of substrate, reagent, catalyst, or solvent), the chirality elements of each reactant will operate either in concert (matched pair) or in opposition (mismatched pair) and together influence the stereochemical outcome of the reaction. In this case, the reaction is subject to double asymmetric induction. Unless the diastereofadal selectivities of both chiral reactants are in opposition and identical in magnitude, the ratio C D 1. Applications of double asymmetric induction in synthesis will be discussed in Chapter 5. 

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