A highly efficient route for the synthesis of valuable 3,4-substituted chromenone derivatives by the reaction of 1,3-diketones with aldehydes in the presence of l-proline was developed. The reactions take advantage of readily available starting materials and follow a Knoevenagel condensation/Michael addition/hemiacetalization domino process. Chiral 3-substituted chromenones are obtained with high enantioselectivities when a chiral diarylprolinol TMS-ether is applied in the reaction.