A Highly Efficient Chirality Switchable Synthesis of Dihydropyran‐Fused Benzofurans by Fine‐Tuning the Phenolic Proton of β‐Isocupreidine (β‐ICD) Catalyst with Methyl

A highly enantioselective β‐isocupreidine (β‐ICD) catalyzed synthesis of dihydropyran‐fused benzofurans through 4+2] cycloaddition of allenoates and benzofuranone alkenes was developed. Switchable chirality inversion of cycloaddition products was achieved by replacing the phenolic proton of the catalyst with a methyl, demonstrating an amazing effect of minimal structural variation on inverting enantioselectivity. DFT calculations were utilized to elucidate the origin of the observed phenomena. Computation also provided a clue for a rational design in which the multi‐hydrogen bond with the alcohol additive was found to improve the enantioselectivity of the cycloaddition. Finally, the substrate scope was examined, in which a number of functionalized dihydropyran‐fused benzofurans could be obtained in high yields (up to 97 %) with very good regio‐ (>20:1) and enantioselectivities (up to 98:2 e.r.).