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Asymmetric photoredox transition-metal catalysis activated by visible light

Abstract

Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical industries1. And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical processes2,3,4,5. For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest2,3,4,5. Photoredox catalysis provides the opportunity to generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions6. In such systems, photoactivated sensitizers initiate a single electron transfer from (or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion7. Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the photoredox centre, offers new opportunities for the ‘green’ synthesis of non-racemic chiral molecules.

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Figure 1: Chiral iridium complexes for asymmetric photoredox catalysis.
Figure 2: Substrate scope of the photoinduced enantioselective alkylation of 2-acyl imidazoles with acceptor substituted benzyl bromides and phenacyl bromides.
Figure 3: Plausible mechanism for a combined photoredox and asymmetric catalysis.
Figure 4: Mechanistic investigations.

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Acknowledgements

We acknowledge funding from the German Research Foundation (ME 1805/4-1). H.H. thanks the China Scholarship Council for a stipend.

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Authors

Contributions

E.M. conceived and coordinated the project and wrote the Letter. E.M. and H.H. designed the experiments. H.H. carried out the majority of the experiments. X.S. synthesized the new catalyst Λ-Ir2. C.W. contributed to the synthesis of substrates. L.Z. contributed to the synthesis and crystallization of iridium complexes. L.-A.C. provided insights into iridium enolate chemistry. P.R. performed and analysed the cyclic voltammetry under supervision of G.H. The X-ray crystallographic studies were performed by K.H. and M.M.

Corresponding author

Correspondence to Eric Meggers.

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The authors declare no competing financial interests.

Additional information

The X-ray crystallographic coordinates for structures of the iridium complex Λ-Ir2, substrate coordinated iridium complex I and the iridium enolate complex II have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers CCDC 1014509, 1014510 and 1014876, respectively.

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Huo, H., Shen, X., Wang, C. et al. Asymmetric photoredox transition-metal catalysis activated by visible light. Nature 515, 100–103 (2014). https://doi.org/10.1038/nature13892

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