This paper describes the successful development of a group of highly efficient chiral tridentate titanium catalysts for hetero-Diels-Alder reaction of Danishefsky's diene and a variety of aldehydes through ligand and additive diversity. Dramatically synergetic effect of carboxylic acid additives and influence of substituent in chiral Schiff base ligands on the enantioselectivities of the reaction are reported. It was found that a chiral drug Naproxen (A21) was a highly efficient additive for Ti-catalyzed HDA reaction, affording 2-substituted 2,3-dihydro-4H-pyran-4-one in up to 97 % ee and >99 % yields. Quantitative study of the effect of chiral carboxylic acid A21 revealed that the reaction could be accelerated by one order of magnitude. Another interesting feature of present catalytic system is the existence of significant positive nonlinear effect, which indicates that the heterochiral Schiff base-titanium complexes may have higher stability than their homochiral counterparts. As a result, the homochiral Schiff base-titanium complexes with higher ee than that of starting ligand will react with carboxylic acid additive to form the more active species and predominate the catalytic process. The isolation and characterization of stable heterochiral ((+/-)-L1)2Ti complex has also been successful, which strongly supported the explanation for positive nonlinear effect observed in the catalytic system.