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Main element chemistry enables gas-cylinder-free hydroformylations


Industrially, aldehydes are produced annually on a multimillion-tonne scale via the hydroformylation of olefins with syngas (CO/H2 mixture). Nonetheless, this transformation has not found frequent use in the laboratory. Here we report on a simple strategy for the concerted generation of syngas from two accessible and crystalline main element compounds with just water as the primary activator for syngas release. By decoupling the syngas formation and consumption via a two-chamber reactor we demonstrate this low-pressure, low-temperature and near-stoichiometric hydroformylation operates efficiently on a diverse array of terminal olefins without the need for expensive equipment. Our approach provides unique opportunities to access aldehydes in a safe and reliable manner with further adaptation to the synthesis of a range of pharmaceuticals and relevant molecules thereof. This strategy is adaptable to carbon isotope labelling as demonstrated by the use of a 13CO releasing molecule. We anticipate this hydroformylation approach will provide a complementary toolbox for drug discovery and development.

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Fig. 1: Hydroformylation reaction and design of a syngas surrogate from main element compounds.
Fig. 2: Pressure measurement studies with the syngas surrogates.
Fig. 3: Evaluation and comparison of the syngas surrogates.
Fig. 4: Scope of the hydroformylation reaction with gas surrogates on various primary alkenes.
Fig. 5: Synthesis and carbon isotope labelling of pharmaceuticals.
Fig. 6: Synthesis of bioactive molecules.

Data availability

The data in support and related to this study is available in the Supplementary Information. Additional data are available from the authors on reasonable request.


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The research reported in this publication was supported by the Danish National Research Foundation (award no. DNRF118), NordForsk (award no. 85378) and Aarhus University.

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Authors and Affiliations



S.K.P., H.G.G., D.U.N., B.S.D., K.D. and H.C.D.H developed the syngas release and the catalytic reactions. S.K.P., D.U.N., H.G.G. and T.S conceived and designed the investigations. T.S. directed and supported the research. S.K.P, H.G.G. and T.S. wrote the manuscript.

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Correspondence to Troels Skrydstrup.

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Competing interests

T.S. is co-owner of SyTracks a/s, which commercializes the two-chamber technology and silacarboxylic acid 2.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–24, Table 1, NMR spectra and references.

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Pedersen, S.K., Gudmundsson, H.G., Nielsen, D.U. et al. Main element chemistry enables gas-cylinder-free hydroformylations. Nat Catal 3, 843–850 (2020).

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