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Selective synthesis of 3-hydroxy acids from Meldrum's acids using SmI2-H2O

Abstract

The single-step synthesis of 3-hydroxy carboxylic acids from readily available Meldrum's acids involves a selective monoreduction using a SmI2-H2O complex to give products in high crude purity, and it represents a considerable advancement over other methods for the synthesis of 3-hydroxy acids. The protocol includes a detailed guide to the preparation of a single electron–reducing SmI2-H2O complex and describes two representative examples of the methodology: monoreduction of a fully saturated Meldrum's acid (5-(4-bromobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione) and tandem conjugate reduction-selective monoreduction of α,β-unsaturated Meldrum's acid (5-(4-methoxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione). The protocol for selective monoreduction of Meldrum's acids takes 6 h to complete.

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Figure 1: Single-step synthesis of 3-hydroxy carboxylic acids from Meldrum's acid derivatives using Sml2-H2O.
Figure 2
Figure 3
Figure 4: Typical solvent degassing setup.
Figure 5: Photograph of the reaction course.

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Acknowledgements

We thank the UK Engineering and Physical Sciences Research Council (EPRSC) and GlaxoSmithKline (GSK) for support.

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All authors designed the protocol, carried out the experiments and co-wrote the paper.

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Correspondence to David J Procter.

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Szostak, M., Spain, M. & Procter, D. Selective synthesis of 3-hydroxy acids from Meldrum's acids using SmI2-H2O. Nat Protoc 7, 970–977 (2012). https://doi.org/10.1038/nprot.2012.034

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