Design of experiments: a rational approach toward non-covalent asymmetric organocatalysis
This Account describes from a personal point of view the possible strategies to tackle and optimize non-covalent organocatalyzed reactions. When chemical intermediates are covalently bound, predictive mechanicistic pictures can be depicted. In contrast, there are several organocatalyzed transformations (e.g. those employing Cinchona alkaloids) for which optimization is essentially based on a trial-and-error approach. The experience of authors is that these reactions can be tackled with a rational approach employing DoE, Design of Experiment.