Kornblum-Delamare rearrangement

What is Kornblum-Delamare rearrangement?

The Kornblum-DeLaMare reaction, first described in 1951, is a base-promoted peroxide rearrangement that produces a ketone and an alcohol. This reaction is also referred to as the Kornblum-DeLaMare rearrangement. In the standard procedure, potassium tert-butyl peroxide and 1-phenylethyl bromide are transformed into tert-butanol and acetophenone in the presence of piperidine, KOH, or NaOEt. Although trialkylamine is commonly used in this reaction, phosphorus ylide and inorganic bases like KOH, LiOH, or sodium ethoxide also work. Recently, even acidic SiO2 has been observed to promote the rearrangement.

Kornblum-Delamare rearrangement - general reaction scheme
Kornblum-Delamare rearrangement
Kornblum-Delamare rearrangement - general reaction scheme
Kornblum-Delamare rearrangement
  • R = Me, Et, etc.
  • n = 1, 2, 3 …

Enantioenriched γ-hydroxyenones are produced via desymmetrization of symmetric bicyclic endoperoxides in the presence of a catalytic amount of chiral base, especially for cinchona, which has shown the best reactivity and enantioselectivity among the tested amines. Peroxides are typically produced through 1,4-dioxygenation of conjugated diene with singlet oxygen (1O2) or photo-[2+2] cycloaddition between singlet oxygen and alkenes, particularly with alkenes activated with an amino or alkoxy group (i.e., enamines or vinyl ethers).

For N-substituted 3-vinylindoles, photo-oxidation with 1O2 efficiently and stereospecifically produces dioxacarbazole endoperoxides. However, [2+2] cycloaddition would occur preferentially at the 3-vinyl double bond when the s-cis conformation is blocked by substituents at the position 2 of indole and the β-position of vinyl moiety. The reaction products depend on the N– and 3-vinyl β-substituents. For example, an electron-withdrawing group on the nitrogen atom of an indole will stabilize the resulting endoperoxide, whereas on the β-carbon of 3-vinyl moiety, it will destabilize the endoperoxide and favor the Kornblum-DeLaMare rearrangement.

Moreover, endoperoxides from N-methyl 3-vinylindole are sensitive to acid and will rearrange to dioxetane, which cleaves the 3-vinyl double bond. The β-methoxy group on 3-vinyl moiety directs the reaction, accelerating endoperoxidation when the aromatic double bond is in a cis-configuration and causing the ene reaction to occur exclusively when a cis-methyl group is present.

References

The Base Catalyzed Decomposition Of A Dialkyl Peroxide
Nathan Kornblum and Harold E. DeLaMare
Journal of the American Chemical Society 1951 73 (2), 880-881
DOI: 10.1021/ja01146a542

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