Three-component reaction discovery enabled by mass spectrometry of self-assembled monolayers

Abstract

Multicomponent reactions are employed extensively in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform that can be used in the identification of new multicomponent transformations. Our approach is based on parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyse a previously unknown condensation of siloxyalkynes, aldehydes and amines to produce 3-hydroxyamides with high efficiency and diastereoselectivity. The reaction was further optimized using solution-phase methods. A general reaction-discovery platform has been used for identification of a new multicomponent transformation. The approach entails rapid analysis of interfacial chemical reactions on arrays of self-assembled monolayers using mass spectrometry. This enabled identification of a simple organic phosphine that catalyses a previously unknown condensation of siloxy alkynes, aldehydes and amines.

Cite this article

Montavon, T., Li, J., Cabrera-Pardo, J. et al. Three-component reaction discovery enabled by mass spectrometry of self-assembled monolayers. Nature Chem 4, 45–51 (2012). https://doi.org/10.1038/nchem.1212

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