α-Halo ketone and strong base: Favorskii vs SN2 [closed]








**Closed**. This question needs to be more [focused](/help/closed-questions). It is not currently accepting answers.
 
 






---








**Want to improve this question?** Update the question so it focuses on one problem only by [editing this post](/posts/114329/edit).




Closed 4 years ago.








[Improve this question](/posts/114329/edit) 



Let us consider an α-halo ketone, with at least one α-H on the α carbon not containing the halogen. If I add a strong base, what is likely to happen: $\mathrm{S\_N2}$ or Favorskii rearrangement?


I have learnt that α-halo carbonyls undergo excellent $\mathrm{S\_N2}$ due to the lowered energy of its LUMO. And the Favorskii is a characteristic of the α-halo carbonyls. How to decide between the two?




I would comment however I am new and have yet to unlock that feature. 


Do you have an exact substrate of interest? I have studied the Favorskii rearrangement a tiny bit in a graduate mechanisms course and if your seeking a very general answer to a general question; The favorskii seems to be favorable when your substrate is containing rings that are conformationally rigid where our alpha-halo-ketone moiety is found.


Check out Eaton's 1964 synthesis of Cubane to find two really elegant Favorskii reactions in the synthesis of Cubane. Notice for almost all of our examples of favorskii reactivity we notice a common pattern in the substrate scope? 


Rings! My theory is conformational rigidity of a ring is partially responsible and we can confidently point our fingers to Favorskii where cyclopropanone intermediates are possible AND energetically favorable (conformation argument). 


If our substrate scope is including non-ring alpha-halo-ketones.. We may want to consider alternatives like SN2 to predict reactivity. 


 2

AS @Karsten Theis pointed out that this question is too broad. Yet, if you are willing to study, here is a review article (Ref.1), which included more than 250 references to go with:



> 
> **Abstract:** The skeletal rearrangement of α-halogeno-ketones, which is known as the Favorskii rearrangement, is met most frequently in aliphatic monocyclic, and polycyclic halogenated ketones. This molecular rearrangement is used in the synthesis of branched carboxylic acids and *cis*-αβ-unsaturated acids and for obtaining smaller rings in alicyclic and to a less extent heterocyclic compounds. The sterochemistry and the mechanism of the Favorskii rearrangement are also considered, these being of great interest for theoretical organic chemistry. A list of 261 references is included.
> 
> 
> 


It is clear that the reaction reaction undergoes Favorskii rearrangement preferably when the substrate is cyclic. The review also discuss on the influences of $\alpha$-$\ce{C}$ on the rearrangement. Recent publication (Ref.2) has shown use of halocycloalkenones as Diels−Alder dienophiles and resulting adduct undergoes Favorskii rearrangement (if you intereted to see). The graphical abstract is shown below: 


[![Favorskii](https://i.stack.imgur.com/zVUT9.gif)](https://i.stack.imgur.com/zVUT9.gif)


**References:**


1. A. A. Akhrem, T. K. Ustynyuk, Yu A. Titov, “The Favorskii Rearrangement,” *Russian Chemical Reviews* **1970**, *39(9)*, 732–746.
2. A. G. Ross, S. D. Townsend, S. J. Danishefsky, “Halocycloalkenones as Diels–Alder Dienophiles. Applications to Generating Useful Structural Patterns,” *J. Org. Chem.* **2013**, *78(1)*, 204–210 (DOI: 10.1021/jo302230m).


 2