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Modular and regioselective synthesis of all-carbon tetrasubstituted olefins enabled by an alkenyl Catellani reaction

Nature Chemistry volume 11, pages 1106–1112 (2019)Cite this article

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Abstract

All-carbon tetrasubstituted olefins have been found in numerous biologically important compounds and organic materials. However, regio- and stereocontrolled construction of this structural motif still constitutes a significant synthetic challenge. Here, we show that a modular and regioselective synthesis of all-carbon tetrasubstituted olefins can be realized via alkenyl halide- or triflate-mediated palladium/norbornene catalysis, which is enabled by a modified norbornene containing a C2 amide moiety. This new norbornene co-catalyst effectively suppressed undesired cyclopropanation pathways, which have previously been a main obstacle for developing such reactions. Diverse cyclic and acyclic alkenyl bromides or triflates with a wide range of functional groups can be employed as substrates. Various substituents can be introduced at the alkene C1 and C2 positions regioselectively simply by changing the coupling partners. Initial mechanistic studies provide insights on the rate-limiting step as well as the structure of the actual active ligand in this system.

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Fig. 1: Representative natural products containing all-carbon tetrasubstituted olefins.
Fig. 2: Alkenyl Catellani-type reactions.
Fig. 3: NBE effect for the alkenyl Catellani reaction.
Fig. 4: Mechanistic studies and synthetic utility.

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Data availability

The data supporting the findings of this study are available within the paper and its Supplementary Information. Crystallographic data for compound 4e have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition no. CCDC 1908383. These data can be obtained free of charge from the CCDC (http://www.ccdc.cam.ac.uk/data_request/cif).

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Acknowledgements

Financial support from the University of Chicago and NIGMS (1R01GM124414-01A1) is acknowledged. We thank K.-Y. Yoon for the X-ray crystallography.

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  1. Department of Chemistry, University of Chicago, Chicago, IL, USA

    Jianchun Wang, Zhe Dong, Cheng Yang & Guangbin Dong

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  1. Jianchun Wang
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Contributions

J.W., Z.D. and G.D. conceived and designed the experiments. J.W. performed experiments. C.Y. prepared a few substrates. J.W. and G.D. co-wrote the manuscript.

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Correspondence to Guangbin Dong.

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Supplementary information

Supplementary information

Experimental procedures, product characterization data, and mechanistic studies

Crystallographic data

Crystallographic data for compound 4e; CCDC reference 1908383

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Wang, J., Dong, Z., Yang, C. et al. Modular and regioselective synthesis of all-carbon tetrasubstituted olefins enabled by an alkenyl Catellani reaction. Nat. Chem. 11, 1106–1112 (2019). https://doi.org/10.1038/s41557-019-0358-y

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