Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization

Abstract

The identification of new reactions expands our knowledge of chemical reactivity and enables new synthetic applications. Accelerating the pace of this discovery process remains challenging. We describe a highly effective and simple platform for screening a large number of potential chemical reactions in order to discover and optimize previously unknown catalytic transformations, thereby revealing new chemical reactivity. Our strategy is based on labelling one of the reactants with a polyaromatic chemical tag, which selectively undergoes a photoionization/desorption process upon laser irradiation, without the assistance of an external matrix, and enables rapid mass spectrometric detection of any products originating from such labelled reactants in complex reaction mixtures without any chromatographic separation. This method was successfully used for high-throughput discovery and subsequent optimization of two previously unknown benzannulation reactions. The development of new reaction methodology is a core activity for organic chemists, but the process can be slow and can rely on serendipity. Here, a reaction discovery platform is described that relies on the labelling of a reaction component with a chemical tag that enables rapid mass spectrometric detection of the derived products in complex mixtures.

Cite this article

Cabrera-Pardo, J., Chai, D., Liu, S. et al. Label-assisted mass spectrometry for the acceleration of reaction discovery and optimization. Nature Chem 5, 423–427 (2013). https://doi.org/10.1038/nchem.1612

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