18087-07-5Relevant articles and documents
Using intelligent/random library screening to design focused libraries for the optimization of homogeneous catalysts: Ullmann ether formation
Fagan, Paul J.,Hauptman, Elisabeth,Shapiro, Rafael,Casalnuovo, Albert
, p. 5043 - 5051 (2000)
A 96-member 'pyridine' library consisting of both rationally chosen and 'random' members was used to screen Ullmann ether forming reactions. The reaction of 2-bromo-4,6-dimethylaniline and other substrates with a variety of alkoxides was investigated under different conditions with the aid of an automated liquid handler. From the results of the 96-member library screening, a structure activity profile was determined which led to the design of smaller 'focused' ligand libraries. The focused libraries produced a higher frequency of hits compared to the original 96-member library. Some of the more effective ligands discovered in this work were found to be generally useful for alkoxylation of a variety of substrates, and also functioned in intramolecular ether forming reactions. This work demonstrates for homogeneous catalysis the analogy to the pharmacological model of drug discovery. By using a large library to screen for a lead compound followed by screening the diversity space closest to the lead, a larger fraction of increased performance ligands was discovered.
