Favorskii and wolff rearrangement seminar

Favorskii rearrangement
Wolff rearrangement

1. Favorskii and Wolff Rearrangements D.V.V. SaiKumar Presented 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 2 FAVORSKII AND WOLFF REARRANGEMENT D efinitio n

3. I ntroductio n : 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. W hich of the product forms ? All the structures shown in the slide are drawn using CHEM BIO DRAW software

7. S teps involved in the mechanis m : 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: Hydroxides like NaOH , KOH etc… to yield a carboxylic acid. Alkoxides to yield an ester. Amines to yield an amide.

9. S ynthetic application s : 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 .

11. F ew example s : Preparation of cubane O Br

12. 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. Recent

13. 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 . Exception

14. K ey feature s : 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.

15. W OLFF REARRANGEMEN T Named after Ludwig Wolff. Wolff rearrangement can be induced via three modes i.e., -Thermal -Photochemical -Transition metal catalysis

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

17. S ynthetic application s : Ring contraction Homologation reactions Cycloaddition reactions Formation of bicyclic compounds

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

21. R eference s : Chem Draw