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Gas-phase sugar formation using hydroxymethylene as the reactive formaldehyde isomer

Nature Chemistry volume 10, pages 1141–1147 (2018)Cite this article

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Abstract

Carbohydrates (CH2O)n are the formal adducts of carbon (atoms) to water with a repeating unit that structurally resembles H–C̈–OH (hydroxymethylene). Although hydroxymethylene has been suggested as a building block for sugar formation, it is a reactive species that had escaped detection until recently. Here we demonstrate that formaldehyde reacts with its isomer hydroxymethylene to give glycolaldehyde in a nearly barrierless reaction. This carbonyl–ene-type transformation operates in the absence of base and solvent at cryogenic temperatures similar to those found in extraterrestrial environments or interstellar clouds. Hydroxymethylene acts as a building block for an iterative sugar synthesis, as we demonstrate through the formation of the triose glyceraldehyde. The thermodynamically preferred ketose dihydroxyacetone does not form, and the formation of further branched sugars in the iterative synthesis presented here is unlikely. The results therefore provide a link between the well-known formose (Butlerow) reaction and sugar formation under non-aqueous conditions.

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Fig. 1: Mechanistic hypotheses related to sugar formation from formaldehyde.
Fig. 2: Mechanistic hypothesis for the uncatalysed ‘carbonyl–ene’ reaction.
Fig. 3: NMR spectra of products resulting from the pyrolysis of glyoxylic acid.
Fig. 4: Reaction of methylhydroxycarbene (3b) with formaldehyde (2a) to hydroxyacetone (1c).
Fig. 5: Reaction mechanism of the carbonyl–ene-type reaction.

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Acknowledgements

This work was supported by the Volkswagen Foundation (‘What is Life’ grant 92 748), the Fonds der Chemischen Industrie (doctoral fellowship to A.K.E.) and the Justus Liebig University (graduate fellowship to M.M.L.). The authors thank H. Hausmann for support with the NMR spectroscopic measurements.

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  1. These authors contributed equally: André K. Eckhardt and Michael M. Linden.

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  1. Institute of Organic Chemistry, Justus Liebig University, Giessen, Germany

    André K. Eckhardt, Michael M. Linden, Raffael C. Wende, Bastian Bernhardt & Peter R. Schreiner

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Contributions

A.K.E. conducted all matrix isolation experiments and carried out all computations. A.K.E., M.M.L., and B.B. carried out all FP experiments. A.K.E. and R.C.W. conducted all data analysis. P.R.S. conceived the original working hypothesis. A.K.E. and P.R.S. wrote the manuscript.

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Correspondence to Peter R. Schreiner.

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Supplementary Figures 1–68, Supplementary Tables 1–6, Supplementary Methods, Supplementary Characterisation Data, Supplementary Computational Data

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Eckhardt, A.K., Linden, M.M., Wende, R.C. et al. Gas-phase sugar formation using hydroxymethylene as the reactive formaldehyde isomer. Nature Chem 10, 1141–1147 (2018). https://doi.org/10.1038/s41557-018-0128-2

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