Designs for explorative experiments in organic synthetic chemistry
The paper highlights different situations encountered when a chemical reaction is to be elaborated into a synthetic method. This includes designs for analysing discrete variations of the reaction space {substrates, reagents, catalysts, solvents...} as well as methods for exploring the variation of the experimental conditions. It is shown how the principal properties of the reaction space can furnish efficient designs for exploring discrete variations. A general strategy based on singular value decomposition of possible combinatory candidate experiment matrices is presented. Methods based on response surface modelling are discussed and a method for determining reaction kinetics by sequential response surface modelling is presented. The chemometrics tools discussed are illustrated by examples from experimental studies in the author's laboratory: The Willgerodt-Kindler reaction, the Leuckart-Wallach reaction, and the Fischer indole synthesis. (C) 2004 Elsevier B.V. All rights reserved.
explorative organic synthetic