Herein we report a new method for the rapid development of catalysts used in enantioselective synthesis of chiral molecules. Our approach is general, does not require immunization pro-[*] Prof.

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The quality of combinatorial libraries determines the success of biological screening in drug discovery programs. In this paper, we evaluate and compare various methods for measuring identity, purity, and quantity (yield) of combinatorial libraries. Determination of quantitative purity reveals the true library quality and often indicates potential quality problems before full-scale library production. The relative purity can be determined for every member in a large library in a high-throughput mode, but must be cautiously interpreted. In particular, many impurities are not observable by relative purity measurements using detectors such as UV(214), UV(254), and evaporative light-scattering detection. These "invisible" impurities may constitute a significant portion of the sample weight. We found that TFA, plastic extracts, inorganic compounds, and resin washout are among these impurities. With compelling evidence, we reach a conclusion that purification is the only way to remove "invisible" impurities and improve the quantitative purity of any compound even though some compounds may have a high relative purity before purification.

An efficient strategy in the search for chiral catalysts is ligand optimization on solid support. This diversity approach provides unique opportunities for the identification of substrate‐specific catalysts and leads to the discovery of ligands with unusual properties that might have otherwise escaped detection. Thus, addition of TMSCN to cyclopentene oxide with ligands 1 or 2, which are very similar, results in opposite enantioselectivities (see reaction on the right; TMS = trimethylsilyl).

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