Tris(pentafluorophenyl)borane-Assisted Chiral Phosphoric Acid Catalysts for Enantioselective Inverse-Electron-Demand Hetero-Diels-Alder Reaction of α,β-Substituted Acroleins

In the enantioselective inverse-electron-demand hetero-Diels-Alder reaction, simple alpha,beta-unsaturated aldehydes (i. e., acroleins) are still challenging substrates, unlike alpha,beta-unsaturated carbonyl compounds containing electron-withdrawing groups. In the present study, the reaction of alpha-aryl-beta-alkyl-substituted acroleins with ethyl vinyl sulfide was developed with the use of bulky chiral supramolecular Bronsted acid catalysts, such as tris(pentafluorophenyl)borane-assisted chiral phosphoric acid catalysts. As a result, cis-cycloadducts as optically active 3,4-dihydro-2H-pyrans were exclusively obtained in high yields with high enantioselectivities via the favored endo orbital approach. An obtained optically active cis-isomer could be transformed into the corresponding trans-isomer without a loss of enantiopurity by O,S-acetal epimerization. Moreover, transformations to synthetically useful optically active epoxide and delta-valerolactone are also demonstrated.