If, however, there is an electronegative atom or group at the site α- to the carbonyl, there is a slight change. This ‘slight change’ is that this electronegative group(X) becomes the equivalent of the ‘large’ group in the Felkin-Ahn model. The reason for this that the energy of the C-X σ* antibonding orbital is rather low, and so it overlaps with the π*of the carbonyl to make a new, lower energy LUMO (lowest unoccupied molecular orbital). This means that this conformational arrangement is more reactive than any other.

A few examples will clarify the case of application of these rules. The major product for the reduction of (R)-2-phenylpropanal can be predicted according to the Cram’s rule (Scheme 9).

Scheme 9

However, to determine the configuration of the product of the reaction between (R)-2-methoxypropanal and dimethyl zinc, the Cram’s chelate rule needs to be applied. In this case a chelate is formed between methoxy group’s oxygen and carbonyl group with zinc (Scheme 10).

 

Scheme 10

Similarly Felkin Anh model is applied for the following example. Here, the large, medium and small groups are phenyl, ethyl and methyl groups, respectively. The attack of hydride (R)-2-phenylpentan-3-one takes from the side of the smallest group (Scheme 11).

Scheme 11