Insights into the Competing Mechanisms and Origin of Enantioselectivity for N-Heterocyclic Carbene-Catalyzed Reaction of Aldehyde with Enamide
نویسندگان
چکیده
Hydroacylation reactions and aza-benzoin reactions have attracted considerable attention from experimental chemists. Recently, Wang et al. reported an interesting reaction of N-heterocyclic carbene (NHC)-catalyzed addition of aldehyde to enamide, in which both hydroacylation and aza-benzoin reactions may be involved. Thus, understanding the competing relationship between them is of great interest. Now, density functional theory (DFT) investigation was performed to elucidate this issue. Our results reveal that enamide can tautomerize to its imine isomer with the assistance of HCO3-. The addition of NHC to aldehydes formed Breslow intermediate, which can go through cross-coupling with enamide via hydroacylation reaction or its imine isomer via aza-benzoin reaction. The aza-benzoin reaction requires relatively lower free energy barrier than the hydroacylation reaction. The more polar characteristic of C=N group in the imine isomers, and the more advantageous stereoelectronic effect in the carbon-carbon bond forming transition states in aza-benzoin pathway were identified to determine that the imine isomer can react with the Breslow intermediate more easily. Furthermore, the origin of enantioselectivities for the reaction was explored and reasonably explained by structural analyses on key transition states. The work should provide valuable insights for rational design of switchable NHC-catalyzed hydroacylation and aza-benzoin reactions with high stereoselectivity.
منابع مشابه
Chiral N-heterocyclic carbene/Lewis acid cooperative catalysis of the reaction of 2-aroylvinylcinnamaldehydes: a switch of the reaction pathway by Lewis acid activation.
The chiral N-heterocyclic carbene/Lewis acid co-catalyzed reaction of 2-aroylvinylcinnamaldehydes produced good yields of indeno[1,2-c]furan-1-one derivatives with excellent enantioselectivity and diastereoselectivity. A switch of intramolecular cyclization to intermolecular dimerization was achieved by the cooperative catalysis of chiral triazole carbene and Ti(OPr-i)4 catalysts.
متن کاملN-heterocyclic carbene-catalyzed [4 + 2] cycloaddition of ketenes and 3-aroylcoumarins: highly enantioselective synthesis of dihydrocoumarin-fused dihydropyranones.
The N-heterocyclic carbene-catalyzed [4 + 2] cyclization of ketenes and 3-aroylcoumarins has been developed to give the corresponding dihydrocoumarin-fused multisubstituted dihydropyranones in high yield with good diastereoselectivity and high enantioselectivity.
متن کاملSynthesis of 1,8-dioxo-octahydroxanthenes under solvent-free conditions via Phosphorus pentoxide supported on alumina (P2O5/Al2O3) catalyzed tandem reaction of Aldehyde with dimedone
Phosphorus pentoxide used on alumina (P2O5/Al2O3) as an inexpensive, eco-friendly and non-toxic acid catalyst for the one-pot synthesis of 1,8-dioxo-octahydroxanthenes via multi-component reactions under solvent-free conditions. The present approach offers several advantages such as short reaction times, high yields, easy purification, recovery and reusability of the catalyst.
متن کاملSynthesis of 1,8-dioxo-octahydroxanthenes under solvent-free conditions via Phosphorus pentoxide supported on alumina (P2O5/Al2O3) catalyzed tandem reaction of Aldehyde with dimedone
متن کامل
Asymmetric borylation of α,β-unsaturated esters catalyzed by novel ring expanded N-heterocyclic carbenes based on chiral 3,4-dihydro-quinazolinium compounds.
A series of chiral 6-membered ring N-heterocyclic carbene (NHC) precursors based on 3,4-dihydro-quinazoline were synthesized with overall yields of 54-62%. NHCs generated from these precursors show excellent asymmetric catalytic properties for borylation of α,β-unsaturated esters with enantioselectivity of up to 93% with a catalyst content of only 1 mol%.
متن کامل