Letter | Published:

Control of four stereocentres in a triple cascade organocatalytic reaction

Nature volume 441, pages 861863 (15 June 2006) | Download Citation

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Abstract

Efficient and elegant syntheses of complex organic molecules with multiple stereogenic centres continue to be important in both academic and industrial laboratories1. In particular, catalytic asymmetric multi-component ‘domino’ reactions, used during total syntheses of natural products and synthetic building blocks, are highly desirable2,3. These reactions avoid time-consuming and costly processes, including the purification of intermediates and steps involving the protection and deprotection of functional groups, and they are environmentally friendly and often proceed with excellent stereoselectivities4,5. Therefore, the design of new catalytic and stereoselective cascade reactions is a continuing challenge at the forefront of synthetic chemistry6. In addition, catalytic cascade reactions can be described as biomimetic, as they are reminiscent of tandem reactions that may occur during biosyntheses of complex natural products7,8. Here we report the development of an asymmetric organocatalytic triple cascade reaction for the synthesis of tetra-substituted cyclohexene carbaldehydes. This three-component domino reaction proceeds by way of a catalysed Michael/Michael/aldol condensation sequence affording the products with good to moderate yields (25–58 per cent). During this sequence, four stereogenic centres are formed with high diastereoselectivity and complete enantioselectivity. In addition, variation of the starting materials can be used to obtain diverse polyfunctional cyclohexene derivatives, which can be used as building blocks in organic synthesis.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (SPP Organokatalyse) and the Fonds der Chemischen Industrie (thanked by C.G. for a Kekulé fellowship). We thank BASF AG, Degussa AG, Bayer AG and Wacker-Chemie for the donation of chemicals, and J. Runsink for the NOE measurements. Author Contributions M.R.M.H. and C.G. contributed equally to this work. The X-ray structure analysis was performed by G.R.

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  1. Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany

    • Dieter Enders
    • , Matthias R. M. Hüttl
    • , Christoph Grondal
    •  & Gerhard Raabe

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Competing interests

Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre, accession number CCDC 295450, and are available via www.ccdc.cam.ac.uk/data_request/cif. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Correspondence to Dieter Enders.

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    Supplementary Notes

    This file contains one figure summarizing the main finding of the manuscript, general information and general procedure of the chemical reactions, analytical data of all synthesized compounds, GC measurements of the reaction course, one figure and X-ray data, two figures.

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https://doi.org/10.1038/nature04820

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