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Catalytic deracemization of chiral allenes by sensitized excitation with visible light

Nature volume 564, pages 240–243 (2018)Cite this article

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Abstract

Chiral compounds exist as enantiomers that are non-superimposable mirror images of each other. Owing to the importance of enantiomerically pure chiral compounds1—for example, as active pharmaceutical ingredients—separation of racemates (1:1 mixtures of enantiomers) is extensively performed2. Frequently, however, only a single enantiomeric form of a chiral compound is required, which raises the question of how a racemate can be selectively converted into a single enantiomer. Such a deracemization3 process is entropically disfavoured and cannot be performed by a conventional catalyst in solution. Here we show that it is possible to photochemically deracemize chiral compounds with high enantioselectivity using irradiation with visible light (wavelength of 420 nanometres) in the presence of catalytic quantities (2.5 mole per cent) of a chiral sensitizer. We converted an array of 17 chiral racemic allenes into the respective single enantiomers with 89 to 97 per cent enantiomeric excess. The sensitizer is postulated to operate by triplet energy transfer to the allene, with different energy-transfer efficiencies for the two enantiomers. It thus serves as a unidirectional catalyst that converts one enantiomer but not the other, and the decrease in entropy is compensated by light energy. Photochemical deracemization enables the direct formation of enantiopure materials from a racemic mixture of the same compound, providing a novel approach to the challenge of creating asymmetry.

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Fig. 1: Reactions of generic chiral compound A and ent-A and structures of compounds 1, ent-1a and 2.
Fig. 2: Optimization of reaction conditions.
Fig. 3: Deracemization of chiral allenes rac-1 by sensitized irradiation with visible light (λ = 420 nm).
Fig. 4: Mechanistic description of deracemization on the basis of DFT calculations, association constants and quantum yields.

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The findings of this study are available within the paper and its Supplementary Information.

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Acknowledgements

Financial support by the Deutsche Forschungsgemeinschaft (DFG) via grant Ba1372/20 and GRK 1626 (T.B.) and through the Cluster of Excellence (EXC 1069) RESOLV project (S.M.H.) is acknowledged. A.H.-H. thanks the research training group (Graduiertenkolleg GRK) 1626 ‘Chemical Photocatalysis’ for a scholarship. A.V.S. acknowledges the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for a post-doctoral research fellowship (BEX number 10744/13-4). C.B. is grateful to S. Grimme for discussions and for admission to computing clusters. We thank O. Ackermann and J. Kudermann for help with the high-performance liquid chromatography and gas–liquid chromatography analyses, A. Strauch for help with the circular dichroism measurements and A. Tröster for compounds for experimental comparison.

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Nature thanks Y. Inoue and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Department Chemie and Catalysis Research Center (CRC), Technische Universität München, Garching, Germany

    Alena Hölzl-Hobmeier, Andreas Bauer, Alexandre Vieira Silva & Thorsten Bach

  2. Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Bochum, Germany

    Stefan M. Huber

  3. Mulliken Center for Theoretical Chemistry, Institut für Physikalische und Theoretische Chemie, Universität Bonn, Bonn, Germany

    Christoph Bannwarth

Authors
  1. Alena Hölzl-Hobmeier
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  2. Andreas Bauer
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  3. Alexandre Vieira Silva
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  5. Christoph Bannwarth
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  6. Thorsten Bach
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Contributions

A.H.-H., A.B. and A.V.S. performed and analysed the experiments. A.H.-H., A.B., A.V.S. and T.B. designed the experiments. A.H.-H., A.B. and T.B. prepared the manuscript. S.M.H. performed all DFT calculations related to complexes 2·ent-1a and 2·1a. C.B. computed the theoretical chiroptical data for compound 1a.

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Correspondence to Thorsten Bach.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

This file contains: General Information; Analytical Methods; Synthetic Procedures and Analytical Data; Optimisation of Irradiation Conditions; Determination of the Absolute Configuration; Details for the DFT Investigations; NMR Spectra; NMR-Titration; Determination of Quantum Yield; Emission Spectra of Catalyst 2; Estimation of Allene Triplet Energy; HPLC Traces; and References.

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Hölzl-Hobmeier, A., Bauer, A., Silva, A.V. et al. Catalytic deracemization of chiral allenes by sensitized excitation with visible light. Nature 564, 240–243 (2018). https://doi.org/10.1038/s41586-018-0755-1

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