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Regioirregular and catalytic Mizoroki–Heck reactions

Nature Catalysis volume 4, pages 293–303 (2021)Cite this article

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Abstract

The palladium-catalysed cross-coupling reaction between alkenes and aryl halides (the Mizoroki–Heck reaction) is a powerful methodology to construct new carbon–carbon bonds. However, the success of this reaction is in part hampered by an extremely marked regioselectivity on the double bond, which dictates that electron-poor alkenes react exclusively on the β-carbon. Here, we show that ligand-free, few-atom palladium clusters in solution catalyse the α-selective intramolecular Mizoroki–Heck coupling of iodoaryl cinnamates, and mechanistic studies support the formation of a sterically encumbered cinnamate–palladium cluster intermediate. Following this rationale, the α-selective intermolecular coupling of aryl iodides with styrenes is also achieved with palladium clusters encapsulated within fine-tuned and sterically restricted zeolite cavities to produce 1,1-bisarylethylenes, which are further engaged with aryl halides by a metal-free photoredox-catalysed coupling. These ligand-free methodologies significantly expand the chemical space of the Mizoroki–Heck coupling.

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Fig. 1: Expanding the chemical space of the Mizoroki–Heck reaction.
Fig. 2: Scope for the α-selective intramolecular coupling.
Fig. 3: DFT calculations of the α-selective intramolecular coupling.
Fig. 4: Pd-containing base zeolites for the α-selective intermolecular coupling.
Fig. 5: Steric effects and in-flow reaction.
Fig. 6: Scope for α-selective intermolecular coupling.

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Data availability

The datasets generated during and/or analysed during the current study are included in this Article (and its Supplementary Information) or are available from the corresponding authors upon reasonable request. If possible, datasets will also be deposited in public repositories of the UPV and CSIC. Source data are provided with this paper.

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Acknowledgements

This work was supported by MINECO (Spain, projects CTQ 2017-86735-P, PID2019-105391GB-C22 and MAT2017-82288-C2-1-P, Severo Ochoa programme SEV-2016-0683 and the Juan de la Cierva programme). F.G.-P. and R.G. thank ITQ for the concession of a contract. J.O.-M. acknowledges the Juan de la Cierva programme for the concession of a contract, and R.P.-R. and J.C.-S. thank the Plan GenT programme (CIDEGENT/2018/044) funded by Generalitat Valenciana. HR STEM measurements were performed at DME-UCA in Cadiz University, with financial support from FEDER/MINECO (PID2019-110018GA-I00 and PID2019-107578GA-I00). We acknowledge ALBA Synchrotron for allocating beamtime and CLÆSS beamline staff for their technical support during our experiment.

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Authors and Affiliations

  1. Instituto de Tecnología Química (UPV-CSIC), Universitat Politècnica de València-Consejo Superior de Investigaciones Científicas, Valencia, Spain

    Francisco Garnes-Portolés, Rossella Greco, Judit Oliver-Meseguer, Mercedes Boronat & Antonio Leyva-Pérez

  2. Departamento de Química, Universitat Politècnica de València, Valencia, Spain

    Jorge Castellanos-Soriano, M. Consuelo Jiménez & Raúl Pérez-Ruiz

  3. Departamento de Ciencia de los Materiales e Ingeniería Metalúrgica y Química Inorgánica, Facultad de Ciencias, Universidad de Cádiz, Campus Universitario Puerto Real, Cádiz, Spain

    Miguel López-Haro & Juan Carlos Hernández-Garrido

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Contributions

F.G.-P. performed the synthesis and characterization of Pd catalysts and the corresponding reactions. R.G. carried out and interpreted the computational studies. J.O.-M. performed and interpreted the synchrotron studies and the in-flow reactions. R.P.-R. and M.C.J. designed and supervised the investigations on photoredox-catalysed coupling between aryl bromides and 1,1-diphenylethylenes. M.L.-H. and J.C.H.-G. carried out and interpreted HR STEM measurements, image analysis and simulations. M.B. carried out and supervised the computational studies. J.C.-S and R.P.-R. performed the photoredox-catalysed reactions together with the isolation, purification and characterization of TAEs. A.L.-P. performed the synthesis and characterization of Pd catalysts and the corresponding reactions, supervised the whole study and wrote the manuscript (all authors contributed to the manuscript).

Corresponding authors

Correspondence to Raúl Pérez-Ruiz or Antonio Leyva-Pérez.

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The authors declare no competing interests.

Additional information

Peer review information Nature Catalysis thanks Ataualpa A. C. Braga, Xiaoning Guo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Scope for the coupling of aryl bromides with polysubstituted ethylenes by means of TFU photoredox catalysis.

Examples of Mizoroki–Heck couplings between aryl bromides and polysubstituted alkenes using TFU technology. Reaction conditions: aryl bromide (10−2 M), polysubstituted alkenes (0.1 M), BOPHY (10−4 M) and DPA (10−3 M), 3 ml of ACN/DMA 5/1 v/v using a blue laser pointer (445 nm ± 10) under nitrogen atmosphere during 5 h. i This reaction was carried out using 2–acetyl–5–chlorothiophene.

Extended Data Fig. 2 Mechanism of the TFU photoredox catalysed Heck coupling of polysubstituted ethylenes.

a, Transient absorption spectra of BOPHY (0.001 mM) and DPA (1 mM) in N2 ACN/DMA (5/1 v/v) solution (λexc = 485 nm). b, Proposed photocatalytic mechanism of the Mizoroki–Heck coupling reaction between aryl bromides and polysubstituted alkenes. Cascade processes involving: ISC (intersystem crossing), TTEnT (triplet–triplet energy transfer), TFU (triplet fusion upconversion), SET (single electron transfer), C‒C bond formation and BET (back electron transfer). c, Delayed emission spectra of a mixture of BOPHY (0.1 mM) and DPA (1 mM) in bubbled (N2) ACN/DMA (5/1 v/v) after excitation (485 nm) with a pulsed laser in the absence (black) and in the presence of 4–bromoacetophenone (10 mM). d, Transient absorption spectrum recorded at 2 μs after the laser pulse of BOPHY (10−4 M) and DPA (10−3 M) in the presence of 4–bromoacetophenone (10−2 M) and 1,1-diphenylethylene (0.1 M) in 3 ml of N2 ACN/DMA (5/1 v/v); inset: decay kinetic monitored at 500 nm after 485 nm TAS.

Supplementary information

Supplementary Information

Supplementary Figs. 1–31, Tables 1–3, Discussion and Methods.

Supplementary Data

Atomic coordinates for the computational calculations, in a flat text file.

Source data

Source Data Fig. 5

Statistical source data.

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Garnes-Portolés, F., Greco, R., Oliver-Meseguer, J. et al. Regioirregular and catalytic Mizoroki–Heck reactions. Nat Catal 4, 293–303 (2021). https://doi.org/10.1038/s41929-021-00592-3

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