Discovery of Exceptionally Efficient Catalysts for Solvent-Free Enantioselective Hetero-Diels−Alder Reaction

Combinatorial coordination chemistry strategy combined with high-throughput screening techniques has been successfully applied to engineering practical enantioselective catalysts for asymmetric hetero-Diels−Alder reaction. The reaction of Danishefsky's diene with a variety of aldehydes can be carried out with 0.1−0.005 mol % of H₄-BINOL/Ti/H₄-BINOL or H₄-BINOL/Ti/H₈-BINOL catalysts at room temperature under solvent- and MS-free conditions to afford dihydropyrone derivatives with up to quantitative yield and 99.8% ee.