6533b820fe1ef96bd127a511
RESEARCH PRODUCT
Understanding the Mechanism of the Intramolecular Stetter Reaction. A DFT Study
José A. SáezRamón J. ZaragozáManuel ArnóLuis R. Domingosubject
Models MolecularStereochemistryPharmaceutical Scienceintramolecular Stetter reactionDFT calculationsArticleCatalysisAnalytical ChemistryStereocenterCatalysislcsh:QD241-441chemistry.chemical_compoundlcsh:Organic chemistryComputational chemistryHeterocyclic CompoundsDrug Discoveryintramolecular Michael additionorganocatalysisN-heterocyclic carbenesPhysical and Theoretical ChemistrymechanismsChemistryOrganic ChemistryStetter reactionorganocatalysis; <em>N</em>-heterocyclic carbenes; <em>umpolung</em> reactivity; intramolecular Stetter reaction; intramolecular Michael addition; mechanisms; DFT calculationsSalicylaldehydeChemistry (miscellaneous)Yield (chemistry)OrganocatalysisIntramolecular forceumpolung reactivityMolecular MedicineCarbeneMethanedescription
The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C s bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addition is the stereoselectivity determining step responsible for the configuration of the stereogenic carbon a to the carbonyl of chromanone 3. An ELF analysis at TSs and intermediates involved in the Michael-type addition allows for the characterization of the electronic changes along the C-C bond-formation.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-02-02 | Molecules |