The Mechanism of the Rappe Rearrangement─A Stereochemical Investigation Using Density Functional Theory.

Area of Science:

• Organic Chemistry
• Reaction Mechanisms

Background:

• The Rappe Rearrangement, involving α,α omino-dibromoketones and aqueous base, yields cis-2-alkenoic acids with unexplained high selectivity.
• Previous hypotheses suggested concerted processes but lacked detailed mechanistic support.

Purpose of the Study:

• To provide a detailed mechanistic explanation for the high stereoselectivity observed in the Rappe Rearrangement.
• To elucidate the reaction pathway leading to thermodynamically less stable cis-2-alkenoic acids.

Main Methods:

• Computational chemistry (density functional theory) was employed to investigate reaction pathways.
• Analysis of transition states and intermediates to determine energy profiles.

Main Results:

• A novel mechanism involving a stereospecific ring closure to a 3-membered cyclopropanone intermediate was identified.
• This intermediate formation follows Woodward-Hoffmann rules for a two-electron allylic cation, with concurrent bromide departure.
• The established stereochemistry is retained during the subsequent ring opening to form the cis-2-alkenoic acid.

Conclusions:

• The proposed mechanism, featuring a cyclopropanone intermediate, accurately explains the observed high selectivity for cis-2-alkenoic acid formation.
• This detailed understanding provides a foundation for exploring new synthetic applications of the Rappe Rearrangement.