Transition-metal-catalysed cross-coupling reactions, particularly those mediated by palladium, are some of the most broadly used chemical transformations. The fundamental reaction steps of such cross-couplings typically include oxidative addition, transmetallation, carbopalladation of a π-bond and/or reductive elimination. Herein, we describe an unprecedented fundamental reaction step: a C–C σ-bond carbopalladation. Specifically, an aryl palladium(ii) complex interacts with a σ-bond of a strained bicyclo[1.1.0]butyl boronate complex to enable addition of the aryl palladium(ii) species and an organoboronic ester substituent across a C–C σ-bond. The overall process couples readily available aryl triflates and organoboronic esters across a cyclobutane unit with total diastereocontrol. The pharmaceutically relevant 1,1,3-trisubstituted cyclobutane products are decorated with an array of modular building blocks, including a boronic ester that can be readily derivatized.
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The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information. Crystallographic data for compounds 5, 7, 15 and 35 are available free of charge from the Cambridge Crystallographic Date Centre (www.ccdc.cam.ac.uk) under reference numbers 1835072, 1847415, 1835073 and 1847416, respectively.
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This work was supported by the EPSRC (EP/I038071/1), H2020 ERC (670668) and the Bayer Science and Education Foundation (Otto–Bayer Fellowship; T.B.). The authors thank E. L. Myers (NUI Galway) and A. Noble for helpful discussions, E. Denton for technical support and H. A. Sparkes for X-ray analysis.
The authors declare no competing interests.
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Fawcett, A., Biberger, T. & Aggarwal, V.K. Carbopalladation of C–C σ-bonds enabled by strained boronate complexes. Nature Chem 11, 117–122 (2019). https://doi.org/10.1038/s41557-018-0181-x
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