Multiple Activation Catalyst for Asymmetric [4+2] Cycloaddition of Aldehydes with Dienes

The enantioselective oxa-Diels-Alder reaction of nonactivated substrates by utilizing FeCl3 and a 1,1'-bi-2-naphthol (BINOL) derived chiral phosphoric acid as a multiple activation catalyst is reported. Various oxygen-containing six-membered heterocycles were obtained in high yields and in an enantioselective manner. Density functional theory (DFT) calculations elucidate that both Lewis acidic and Bronsted acidic moieties in the catalyst system synergistically activate two lone pairs of an aldehyde to facilitate enantioselective addition reaction of dienes.

Automated summary

The enantioselective oxa-Diels-Alder reaction of nonactivated substrates using FeCl3 and a 1,1'-bi-2-naphthol (BINOL) derived chiral phosphoric acid as a multiple activation catalyst was successfully achieved in this study. Various oxygen-containing six-membered heterocycles were synthesized in high yields and in an enantioselective manner. Density functional theory (DFT) calculations revealed the synergistic activation of two lone pairs of an aldehyde by both Lewis acidic and Bronsted acidic moieties in the catalyst system to facilitate enantioselective addition reaction of dienes.