A Ligand Structure-Activity Study of DNA-Based Catalytic Asymmetric Hydration and Diels-Alder Reactions.

A structure-activity relationship study of the first generation ligands for the DNA-based asymmetric hydration of enones and Diels-Alder reaction in water is reported. The design of the ligand was optimized resulting in a maximum ee of 83% in the hydration reaction and 75% in the Diels-Alder reaction, and some guidelines for ligand design were formulated. A comparison between these two reaction classes using salmon testes DNA/Cu(2+)-L catalysts, showed that the enantioselectivity in the hydration reaction was not the result of selective shielding of one pi face of the enone. In contrast, the structure of the ligand was suggested to be crucial to position and orient the substrate bound Cu(2+) complex optimally with respect to the structured first hydration layer of the DNA. Likely, the DNA activates and directs the H(2)O nucleophile for attack to one preferred pi face of the enone.