Favorskii rearrangement Wolff rearrangement

1. Favorskii and Wolff
Rearrangements
D.V.V. SaiKumarPresented By:

2. • The Favorskii rearrangement is most principally
a base-catalyzed rearrangement of cyclo propanones
and α-halo ketones which leads to carboxylic acid
derivatives.
• This rearrangement is named after the Russian chemist Alexei
Yevgrafovich Favorskii.
• This rearrangement was thought to be just a variant of the benzilic
acid rearrangement until 1944 when they found that the ….
1/17/2020 2FAVORSKII AND WOLFF REARRANGEMENT
Definition

3. Introduction:
• This rearrangement was thought to be just a variant of the benzilic
acid rearrangement until 1944 when they found that the ….
• Two structural isomers of α-chloro ketone gave the same product on
treatment with methoxide.

4. • It was deduced that these molecules passed through the same
intermediate and slowly the mechanism of this rearrangement
evolved.
• The reaction mechanism is thought to involve the formation of an
enolate on the side of the ketone away from the chlorine atom; this
enolate cyclizes to a cyclopropanone intermediate which is then
attacked by the hydroxide nucleophile.

5. 2 e- disrotatory
electrocyclic reaction

6. Which of the product forms?
All the structures shown in the slide are drawn using CHEM BIO DRAW software

7. Steps involved in the mechanism:
• Formation of enolate.
• Formation of oxyallyl cation.
• Formation of cyclopropanone intermediate by pericyclic reaction.
• Nucleophilic attack.
• Rearrangement step.
• Protonation.

8. This rearrangement takes place in the presence of a base:
1) Hydroxides like NaOH , KOH etc… to yield a carboxylic acid.
2) Alkoxides to yield an ester.
3) Amines to yield an amide.

9. Synthetic applications:
• In the case of cyclic α-halo ketones, the Favorskii rearrangement
constitutes a ring contraction.

10. • α,α’-Dihaloketones eliminate HX under the reaction conditions to
give α,β-unsaturated carbonyl compounds.

12. Few examples:
• Preparation of cubane
O
Br

13. Halocycloalkenones as Diels-Alder Dienophiles. Applications to Generating Useful Structural Patterns
A. G. Ross, S. D. Townsend, S. J. Danishefsky, J. Org. Chem., 2013, 78, 204-210.
R
e
c
e
n
t

14. When enolate formation is impossible, the Favorskii rearrangement
takes place by an alternate mechanism, in which addition to hydroxide
to the ketone takes place, followed by concerted collapse of the
tetrahedral intermediate and migration of the neighboring carbon with
displacement of the halide; this is sometimes known as the
pseudo-Favorskii rearrangement.
E
x
c
e
p
t
i
o
n

15. Key features:
• Favorskii rearrangement is of the type in which the migration
terminus is an electron rich carbon.
• The carbonyl group is formed at the migration origin.
• Wide variety of options available regarding the base for
rearrangement.
• Alkoxide acts as a base while enolizing the ketone and as a
nucleophile in the rearrangement step.
• The overall consequence of the rearrangement is the alkyl group is
shifted from one of the carbonyl to the other.

16. WOLFF REARRANGEMENT
• Named after Ludwig Wolff.
• Wolff rearrangement can be induced via
three modes i.e.,
-Thermal
-Photochemical
-Transition metal catalysis

17. Type Migratory aptitude
Thermal H > aryl ≥ alkyl
Photochemical H > alkyl ≥ aryl
Transition metal catalysis H > aryl ≥ alkyl

18. Synthetic applications:
•Ring contraction
•Homologation reactions
•Cycloaddition reactions
•Formation of bicyclic compounds

19. Case study of Cotton pest problem
Boll weevil

20. Solution has come soon!!!
Efforts to cultivate boll weevil
resistant cotton plants failed
Grandisol

21. • Carbonyl group formation at migration origin
• Wide number of applications
• Varied choices of bases/nucleophiles
• 1,2-rearrangement
• Overall consequence
• Intermediate involved
• Migration type

22. References:
Chem Draw