Cram’s rule of asymmetric induction
> When a molecule with one or more chiral centers creates a new one, two diastereomers are
generated in unequal proportions. Such reaction is called Asymmetric synthesis and the
existing chiral center is said to bring about asymmetric induction.
Cram’s rule organic chemistry
Cram’s rule helps to predict the stereochemistry of the nucleophilic addition to a carbonyl
group with an adjacent chiral center. The best conformation for nucleophilic addition to
carbonyl compounds with an adjacent chiral center (without polar groups) is considered to be
one that minimizes the interaction during the entry of the nucleophilic group between the
largest group and the carbonyl group reagent. When a ketonic group attached to a chiral center
having a large, a medium and a small group undergoes nucleophilic addition with
organometallic or metal hydride reagents, two diastereomeric products result. Among these
two diastereomeric products( erythro and threo), one predominates. In such a case, the
relative configuration of the predominant isomer is predicted by Cram’s rule based on some
arbitrary models.
Basic guidelines of Cram’s Rule
The basic steps in Cram’s rule are explained below.
[Link] of all, assign the Large group(L), Medium(M) and small(S) groups at the chiral center.
[Link] the orientation of Large group with carbonyl group. If L group is syn to carbonyl group then, nucleophile will attack
from the side similar to medium group.
[Link] L group is Anti to carbonyl group then, nucleophile will attack from the side similar to smaller group
Cram’s rule example
2-phenyl propionaldehyde when treated with Methyl magnesium Bromide(CH 3MgBr), erythro-3-phenyl
butane-2-ol is obtained as the major product. Let’s see an example.
Application of Cram’s Rule
When benzoin having S OR R configuration is reduced with lithium aluminum hydride, meso-hydrobenzoin is obtained as the
major product. This can be explained by using Cram’s rule.