Combinatorial chemistry approach to chiral catalyst engineering and screening: rational design and serendipity.
An efficient asymmetric catalyst relies on the successful combination of a large number of interrelated variables, including rational design, intuition, persistence, and good fortune-not all of which are necessarily well-understood; this renders such practice largely empirical. As a result, the possibility of using combinatorial chemistry methods in asymmetric catalysis research has been widely recognized to be highly desirable. In this account, we attempt to show the principle and application of combinatorial approach in the discovery of chiral catalysts for enantioselective reactions. The concept focuses on the strategy for the creation of a modular chiral catalyst library by two-component ligand modification of metal ions on the basis of molecular recognition and assembly. The self-assembled chiral catalyst with two different ligands indeed exhibited synergistic effects in terms of both enantioselectivity and activity in comparison with its corresponding homocombinations in many reactions. The examples described in this paper demonstrated the powerfulness of combinatorial approach for the discovery of novel chiral catalyst systems, particularly for the development of highly efficient, enantioselective, and practical catalysts for enantioselective reactions. We hope this concept will stimulate further work on the discovery of more highly efficient and enantioselective catalysts, as well as unexpected classes of catalysts or catalytic enantioselective reactions in the future with the help of a combinatorial chemistry approach.
Ding
Kuiling
K
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P R China. kding@mail.sioc.ac.cn
Du
Haifeng
H
Yuan
Yu
Y
Long
Jiang
J
D002384:Catalysis; D002626:Chemistry, Pharmaceutical; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D008024:Ligands; D013237:Stereoisomerism
D008024:Ligands