Felkin-Anh Model

  • Overview: Predicts the stereochemical outcome of nucleophilic addition to a carbonyl compound. The model suggests that the nucleophile attacks at an angle (Bürgi-Dunitz trajectory), favoring the least sterically hindered face of the carbonyl.
  • Key Features:
    • Large substituents orient anti to the carbonyl group (minimizing steric hindrance).
    • Explains the formation of major diastereomers in reactions like aldol or Grignard additions.
  • Variants: The Cram's Rule is a precursor but less nuanced than Felkin-Anh.

 

The largest group (determined using the A value table for steric bulk) prefers a conformation where it is positioned perpendicular to the carbonyl C=O bond. This results in two closely competing low-energy conformations, where the medium and smallest groups alternate in their proximity to the carbonyl oxygen.

 

The nucleophiles does not attack at a 90° angle to the C=O bond but at an angle closer to the tetrahedral bond angle (approximately 107°). This trajectory of approach is known as the Bürgi-Dunitz trajectory. Predictably, the nucleophile favors an approach that avoids the steric hindrance of the largest group.

This leaves two possible attack pathways: one where the nucleophile approaches closest to the smallest group, and another where it approaches nearest to the medium group. The nucleophile preferentially attacks closer to the smallest group, leading to the formation of a specific diastereomer as the major product.

In most cases (though not universally), the largest group becomes part of the main chain in the product, while the incoming nucleophile forms the other end of the main chain. Under these conditions, the major diastereomer is typically the syn-diastereomer.

 

If there is an electronegative atom or group at the α-position to the carbonyl, the Felkin-Anh model undergoes a slight adjustment. For this discussion, electronegative groups (X) are limited to halogens, OR, NR₂, or SR groups. In such cases, the electronegative group effectively becomes the "large" group in the Felkin-Anh model.

The energy of the C-X σ* antibonding orbital is relatively low, allowing it to overlap with the π* orbital of the carbonyl. This interaction creates a new, lower-energy LUMO (lowest unoccupied molecular orbital), making this specific conformational arrangement more reactive than others.

With this shift, the Felkin-Anh addition proceeds similarly to before. However, in most cases (though not universally), the "medium" group ends up incorporated into the product's main chain. As a result, the anti-diastereomer is typically favored in these reactions.