Enantioselective Synthesis of α‐Aryl Ketones by a Cobalt‐Catalyzed Semipinacol Rearrangement

A highly enantioselective cobalt‐catalyzed semipinacol rearrangement of symmetric α,α‐diarylallylic alcohols is disclosed. A chiral cobalt‐salen catalyst generates a highly electrophilic carbocation surrogate following hydrogen atom transfer and radical–polar crossover steps. This methodology provid...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2025-01, Vol.64 (2), p.e202414342-n/a
Main Authors: Kalomenopoulos, Panagiotis G., Emayavaramban, Balakumar, Johnston, Craig P.
Format: Article
Language:English
Subjects:
Alcohols
Aromatic compounds
Cations
Chemical synthesis
Cobalt
Cobalt Catalysis
Enantiomers
Enantioselective
Hydrogen atoms
Ketones
Oxidants
Oxidizing agents
Phenonium Ion
Reagents
Semipinacol Rearrangement
Substitution reactions
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Summary:A highly enantioselective cobalt‐catalyzed semipinacol rearrangement of symmetric α,α‐diarylallylic alcohols is disclosed. A chiral cobalt‐salen catalyst generates a highly electrophilic carbocation surrogate following hydrogen atom transfer and radical–polar crossover steps. This methodology provides access to enantioenriched α‐aryl ketones through invertive displacement of a cobalt(IV) complex during 1,2‐aryl migration. A combination of readily available reagents, silane and N‐fluoropyridinium oxidant, are used to confer this type of reactivity. An exploration into the effect of aryl substitution revealed the reaction tolerates para‐ and meta‐halogenated, mildly electron‐rich and electron‐poor aromatic rings with excellent enantioselectivities and yields. The yield of the rearrangement diminished with highly electron‐rich aryl rings whereas very electron‐deficient and ortho‐substituted arenes led to poor enantiocontrol. A Hammett analysis demonstrated the migratory preference for electron‐rich aromatic rings, which is consistent with the intermediacy of a phenonium cation. A chiral cobalt‐salen catalyst has been used under mild, oxidative conditions to generate a cobalt(IV)‐bound intermediate that is sufficiently electrophilic to promote an enantioselective 1,2‐aryl migration. The excellent levels of stereocontrol and a Hammett analysis provide key evidence for the involvement of the cobalt catalyst in this cationic hydro‐semipinacol rearrangement.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202414342