Скачать или смотреть Anti-Cram’s Rule in Organic Chemistry – Definition, Mechanism | Stereoselective synthesis Shortcut

What is Anti-Cram’s Rule?
You already know about Cram’s Rule, which predicts that in nucleophilic addition to a carbonyl group, the nucleophile attacks opposite to the largest group at the adjacent chiral center.

But sometimes, reactions don’t follow this rule. Instead, the nucleophile attacks from a different side due to electronic effects (not just steric hindrance).

👉 This exceptional case is called the Anti-Cram’s Rule (also known as the Cram’s Chelate Model).
Why Does Anti-Cram’s Rule Happen?
Cram’s Rule focuses mainly on size of groups (steric effects).
Anti-Cram’s Rule considers electronic effects, especially when there is a group near the carbonyl that can coordinate (bind) with a metal or nucleophile.
This coordination changes the orientation of the molecule and allows attack from the opposite side compared to what Cram’s Rule predicts.

The Key Idea
When an electron-donating substituent (like –OCH₃, –OH, –NH₂) is present on the chiral carbon near the carbonyl group, it can form a chelate (a ring by binding with metal/nucleophile).
This chelation locks the molecule in a different geometry.
In this geometry, the nucleophile attacks from a direction opposite to Cram’s prediction.
This new stereochemical outcome is explained by the Anti-Cram’s Rule.

Mechanism, Example, and Exam Notes
Mechanism of Anti-Cram’s Rule
Consider a carbonyl compound with a chiral carbon next to it.
If that chiral carbon has an electron-donating substituent (EDG), like –OCH₃, it can interact with the metal atom of the nucleophile (for example, Mg²⁺ from a Grignard reagent).
This interaction forms a five-membered chelate ring.
The chelation fixes the orientation of the molecule so that the nucleophile attacks from the opposite side compared to normal Cram’s Rule.
The product formed is called the Anti-Cram product.

Example
Take a carbonyl compound with a chiral center:
R–CH(OMe)–C(=O)R'
Here, the –OMe group is electron-donating.
If a Grignard reagent (RMgX) attacks, the Mg²⁺ can coordinate with the O atom of –OMe.
This creates a chelated structure.
Because of this chelation, the nucleophile attacks in a direction different from Cram’s Rule, giving the Anti-Cram product.
Difference Between Cram’s Rule and Anti-Cram’s Rule
Cram’s Rule: Nucleophile attacks opposite to the largest group → steric effect dominates.

Anti-Cram’s Rule: Chelation with electron-donating group changes orientation → electronic effect dominates.

Key Points for Exams (NEET/JEE/Boards)
Anti-Cram’s Rule is also called the Chelation Model.
It occurs when there is an electron-donating substituent near the carbonyl group.
Chelation controls the attack direction of nucleophiles.
The major product is opposite to what Cram’s Rule predicts.
Important in reactions of carbonyl compounds with Grignard reagents.

✅ Exam Tip (Summary):
If only steric effects matter → follow Cram’s Rule.
If chelation is possible with electron-donating groups → follow Anti-Cram’s Rule.