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Rhodium-catalysed syn-carboamination of alkenes via a transient directing group

Nature volume 527, pages 86–90 (2015)Cite this article

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Abstract

Alkenes are the most ubiquitous prochiral functional groups—those that can be converted from achiral to chiral in a single step—that are accessible to synthetic chemists. For this reason, difunctionalization reactions of alkenes (whereby two functional groups are added to the same double bond) are particularly important, as they can be used to produce highly complex molecular architectures1,2. Stereoselective oxidation reactions, including dihydroxylation, aminohydroxylation and halogenation3,4,5,6, are well established methods for functionalizing alkenes. However, the intermolecular incorporation of both carbon- and nitrogen-based functionalities stereoselectively across an alkene has not been reported. Here we describe the rhodium-catalysed carboamination of alkenes at the same (syn) face of a double bond, initiated by a carbon–hydrogen activation event that uses enoxyphthalimides as the source of both the carbon and the nitrogen functionalities. The reaction methodology allows for the intermolecular, stereospecific formation of one carbon–carbon and one carbon–nitrogen bond across an alkene, which is, to our knowledge, unprecedented. The reaction design involves the in situ generation of a bidentate directing group and the use of a new cyclopentadienyl ligand to control the reactivity of rhodium. The results provide a new way of synthesizing functionalized alkenes, and should lead to the convergent and stereoselective assembly of amine-containing acyclic molecules.

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Figure 1: Carboamination reactions.
Figure 2: Working hypothesis: tuning of the directing group to influence reactivity.
Figure 3: Applications of the carboamination reaction.
Figure 4: Study and proposed reaction mechanism.

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Acknowledgements

We thank the National Institute of General Medical Sciences (grant no. GM80442) for support. We thank Johnson Matthey for rhodium salts, and J. Chu and B. Newell (at Colorado State University) for solving X-ray structures.

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Authors and Affiliations

  1. Department of Chemistry, Colorado State University, Fort Collins, 80523, Colorado, USA

    Tiffany Piou & Tomislav Rovis

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  1. Tiffany Piou
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  2. Tomislav Rovis
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Contributions

T.P. and T.R. conceived the concept and prepared the manuscript. T.R. directed the investigations. T.P. developed and studied the reaction.

Corresponding author

Correspondence to Tomislav Rovis.

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The authors declare no competing financial interests.

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Piou, T., Rovis, T. Rhodium-catalysed syn-carboamination of alkenes via a transient directing group. Nature 527, 86–90 (2015). https://doi.org/10.1038/nature15691

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