An efficient one-pot synthesis of functionalized 2-amino-4H-pyrans by a meglumine-catalyzed three-component reaction has been developed. A broad range of substrates including aromatic and heteroaromatic aldehydes, isatin derivatives, and acenaphthenequinone are condensed with enolizable C-H activated compounds and alkylmalonates to give the desired products in high to excellent yields. This methodology provides an alternative approach for rapid access to construct a diversity-oriented library of 4H-pyrans.