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CO- and HCl-free synthesis of acid chlorides from unsaturated hydrocarbons via shuttle catalysis

Abstract

The synthesis of carboxylic acid derivatives from unsaturated hydrocarbons is an important process for the preparation of polymers, pharmaceuticals, cosmetics and agrochemicals. Despite its industrial relevance, the traditional Reppe-type carbonylation reaction using pressurized CO is of limited applicability to laboratory-scale synthesis because of: (1) the safety hazards associated with the use of CO, (2) the need for special equipment to handle pressurized gas, (3) the low reactivity of several relevant nucleophiles and (4) the necessity to employ different, often tailor-made, catalytic systems for each nucleophile. Herein we demonstrate that a shuttle-catalysis approach enables a CO- and HCl-free transfer process between an inexpensive reagent, butyryl chloride, and a wide range of unsaturated substrates to access the corresponding acid chlorides in good yields. This new transformation provides access to a broad range of carbonyl-containing products through the in situ transformation of the reactive acid chloride intermediate. In a broader context, this work demonstrates that isodesmic shuttle-catalysis reactions can unlock elusive catalytic reactions.

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Figure 1: Conceptual blueprint for the development of a CO- and HCl-free synthesis of acid chlorides via shuttle catalysis.
Figure 2: Applications of the hydrochlorocarbonylation reaction.
Figure 3: Labelling studies.

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Acknowledgements

We thank E. M. Carreira, B. Bhawal, M. Schafroth, Z. K. Wickens and N. Armanino for critical proofreading of this manuscript. Generous funding from the Max-Planck-Society, the Max-Planck-Institut für Kohlenforschung, the Otto Röhm Gedächtnisstiftung and the Fonds der Chemischen Industrie are acknowledged. We thank B. List for sharing analytical equipment and our mass spectrometry department for technical assistance.

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B.M. and X.F. conceived the project and designed the experiments. X.F. and B.C. performed the experiments and analysed the data. B.M. and X.F. wrote the manuscript. All the authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Bill Morandi.

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The authors declare no competing financial interests.

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Fang, X., Cacherat, B. & Morandi, B. CO- and HCl-free synthesis of acid chlorides from unsaturated hydrocarbons via shuttle catalysis. Nature Chem 9, 1105–1109 (2017). https://doi.org/10.1038/nchem.2798

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