Double‐layered mesoporous silica was prepared for use as an efficient support for the encapsulation of chiral salen Co‐BF3 complexes in the pore channels. The heterogenized chiral salen complex was applied successfully to the asymmetric ring opening (ARO) of terminal epoxides using water, alcohols, and carboxylic acids as nucleophiles. Although the homogeneous salen catalyst exhibited higher catalytic activity than the heterogenized catalyst in ARO reactions as expected, the heterogeneous salen catalysts exhibited high catalytic activities that were sufficient for practical applications. This study evaluated the unique contribution of ultrasonic irradiation as a powerful mixing medium to improve the kinetics in comparison to conventional mechanical agitation during the ARO reactions. Both the homogeneous and heterogeneous chiral salen complexes catalyzed enantioselectively the racemic or chiral epoxides under ultrasonication. The adoption of ultrasonic irradiation in the catalysis resulted in a superior mixing effect to vigorous mechanical stirring. The reaction time was shortened to obtain the highest enantiomeric excess (%ee) when ultrasonic irradiation was applied to the reaction system. Through the ARO reaction of epoxide by phenol derivatives, the highly enantio‐enriched β‐blockers could be synthesized easily from racemic terminal epoxides or chiral ones using chiral cobalt–salen catalysts. The regioselective ARO reaction of (R)‐ECH with propionic or butyric acid proceeded smoothly at room temperature under ultrasonic exposure in the presence of the heterogenized catalyst. The corresponding glycidyl alkylates were produced with excellent optical purity of up to 98%ee. The chiral cobalt–salen complexes encapsulated in MCM‐41 retained its catalytic activity and enantioselectivity for three recycles. Consequently, the heterogeneous chiral catalysts anchored in MCM‐41 offered the practical advantages of facile reuse through simple recovery from the reactant and products.