A new method for the synthesis of 4H-chromene derivatives using Zn@SBA-15 was investigated. The one-pot multicomponent reaction of dimedone, acetylenic esters 1, and isocyanides 2 in the presence of this catalyst afforded a single product, assigned as the 4H-chromene derivative 3. The use of readily available starting materials and non-toxic zinc salt for the preparation of Zn@SBA-15, together with its excellent ability to direct the reaction toward a single product, represents a clear advantage. Beyond the usual role of a catalyst in improving yield and reducing reaction time, Zn@SBA-15 also enabled the creation of a simple work-up procedure. Accordingly, the final products 3 were purified easily by a two-solvent procedure, without the need for using column chromatography or hazardous organic solvents. After optimization of the reaction conditions, the process was readily scaled up to 10 mmol. In this report, the detailed preparation of the catalyst and the gram-scale procedure for the synthesis of 4H-chromenes are described. FESEM images confirmed the nanoscale morphology of the synthesized catalyst, and the structures of the final products were characterized and elucidated using spectroscopic methods.