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

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.