Cram s rule problem

If stoichiometric quantities of the chiral auxiliary are used (i.e., if the chiral auxiliary is covalently bonded to the molecule bearing the prochiral centres) there are in principle three possible ways of achieving stereoselection in an aldol adduct i) condensation of a chiral aldehyde with an achiral enolate ii) condensation of an achiral aldehyde with a chiral enolate, and iii) condensation of two chiral components. Whereas Evans [14] adopted the second solution, Masamune studied the "double asymmetric induction" approach [22aj. In this context, the relevant work of Heathcock on "relative stereoselective induction" and the "Cram s rule problem" must be also considered [23]. The use of catalytic amounts of an external chiral auxiliary in order to create a local chiral environment, will not be considered here. 

Relative stereoselective induction and the "Cram s rule problem" "Double stereodifferentiation ". 

We have examined a purely logical way in which the "Cram s rule problem" can be attacked — double stereodifferentiation. For example, either reactant in an aldol condensation can be chiral and exhibit diastereoface selectivity. Suppose we have an aldehyde which reacts with achiral enolates to give the two possible erythro adducts in a 10 1 ratio ... 

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