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Atroposelective synthesis of tetra-ortho-substituted biaryls by catalyst-controlled non-canonical polyketide cyclizations

Nature Catalysis volume 2, pages 925–930 (2019)Cite this article

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Abstract

The cyclization of poly-β-carbonyl-substrates controlled by polyketide synthases intricately governs the biosynthesis of a wide range of aromatic polyketides. Analogous small-molecule-catalysed processes would conceivably induce selective cyclizations of non-canonical polycarbonyl substrates to provide products distinct from natural polyketides. Here, we report a secondary amine-catalysed twofold cyclization of non-canonical hexacarbonyl substrates, furnishing enantioenriched tetra-ortho-substituted binaphthalenes. The substrates were prepared by a fourfold ozonolysis of dicinnamyl biindenes and converted under catalyst control with high atroposelectivity. Privileged catalysts, helicenes and ligands are readily accessible from the binaphthalene products stemming from the non-canonical polyketide cyclizations.

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Fig. 1: Biosynthesis of aromatic polyketides and catalytic non-canonical polyketide cyclization.
Fig. 2: The preparation of substrates.
Fig. 3: Conditions for the synthesis of a chiral diene ligand, the Maruoka ion-pairing catalyst and a [5]helicene.

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Data availability

The synthetic procedures and characterization data are available in the Supplementary Information. Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under nos. 1856452 (for (Ra)-4a prepared with (R)-6a, reflection shown in Table 2), 1856453 (for (Sa)-4c) and 1856454 (for (Sa)-4e) and can be obtained free of charge from the CCDC via www.ccdc.cam.ac.uk/getstructures. All other data are available from the authors upon reasonable request.

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Acknowledgements

We acknowledge financial support from the Swiss National Science Foundation (BSSGI0-155902/1), the University of Basel and the NCCR Molecular Systems Engineering and thank F. Zellweger and F. Bianchi for skilful technical work, T. Müntener for NMR assistance and M. Neuburger for X-ray crystallography.

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Authors and Affiliations

  1. Department of Chemistry, University of Basel, Basel, Switzerland

    Reto M. Witzig, Vincent C. Fäseke, Daniel Häussinger & Christof Sparr

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  2. Vincent C. Fäseke
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  3. Daniel Häussinger
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Contributions

R.M.W. developed the substrate synthesis and identified the aldolization modes. R.M.W. and V.C.F. optimized the described synthetic method. R.M.W. investigated the scope. R.M.W. and V.C.F. synthesized the ligand, helicene and catalyst. D.H. investigated the substrate tautomerism and mechanism by NMR. C.S. conceived and supervised the project. All authors contributed to the preparation of the manuscript.

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Correspondence to Christof Sparr.

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Supplementary information

Supplementary Information

Supplementary methods, Supplementary Table 1, Supplementary Fig. 1 and Supplementary references

Compound (Ra)-4a

Crystallographic data for compound (Ra)-4a

Compound (Sa)-4c

Crystallographic data for compound (Sa)-4c

Compound (Sa)-4e

Crystallographic data for compound (Sa)-4e

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Witzig, R.M., Fäseke, V.C., Häussinger, D. et al. Atroposelective synthesis of tetra-ortho-substituted biaryls by catalyst-controlled non-canonical polyketide cyclizations. Nat Catal 2, 925–930 (2019). https://doi.org/10.1038/s41929-019-0345-0

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