Visible-light excitation of iminium ions enables the enantioselective catalytic β-alkylation of enals

Abstract

Chiral iminium ions—generated upon condensation of α,β-unsaturated aldehydes and amine catalysts—are used extensively by chemists to make chiral molecules in enantioenriched form. In contrast, their potential to absorb light and promote stereocontrolled photochemical processes remains unexplored. This is despite the fact that visible-light absorption by iminium ions is a naturally occurring event that triggers the mechanism of vision in higher organisms. Herein we demonstrate that the direct excitation of chiral iminium ions can unlock unconventional reaction pathways, enabling enantioselective catalytic photochemical β-alkylations of enals that cannot be realized via thermal activation. The chemistry uses readily available alkyl silanes, which are recalcitrant to classical conjugate additions, and occurs under illumination by visible-light-emitting diodes. Crucial to success was the design of a chiral amine catalyst with well-tailored electronic properties that can generate a photo-active iminium ion while providing the source of stereochemical induction. This strategy is expected to offer new opportunities for reaction design in the field of enantioselective catalytic photochemistry.

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Figure 1: Reactivities of iminium ions in biological systems and enantioselective catalytic synthesis.
Figure 2: Design plan and mechanistic proposal: exploiting the direct photoexcitation of transiently generated chiral iminium ions I to enable stereocontrolled photochemical processes.
Figure 3: Photophysical and structural characterization of iminium ions and mechanistic investigations.

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Acknowledgements

Financial support was provided by the CERCA Programme (Generalitat de Catalunya), MINECO (Severo Ochoa Excellence Accreditation 2014-2018, SEV-2013-0319), and the European Research Council (ERC-2015-CoG 681840 - CATA-LUX). C.V. thanks the Marie Skłodowska-Curie Actions for a postdoctoral fellowship (H2020-MSCA-IF-2014 658980). L.B. thanks MINECO for a predoctoral fellowship (CTQ2013-45938-P). The authors thank M. Moliterno for helpful discussions. This work is dedicated to V. Balzani on the occasion of his 80th birthday.

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M.S. was involved in the discovery and initial development of the light-driven reactions. C.V. and Y.P.R. designed and synthesized the catalysts. C.V., Y.P.R. and L.B. performed the experiments. All of the authors analysed the data and designed the experiments. P.M directed the project and wrote the manuscript with contributions from all of the authors.

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Correspondence to Paolo Melchiorre.

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The authors declare no competing financial interests.

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Crystallographic data for compound 1c. (CIF 2371 kb)

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Crystallographic data for compound 5a. (CIF 2802 kb)

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Crystallographic data for compound Ic. (CIF 1815 kb)

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Silvi, M., Verrier, C., Rey, Y. et al. Visible-light excitation of iminium ions enables the enantioselective catalytic β-alkylation of enals. Nature Chem 9, 868–873 (2017). https://doi.org/10.1038/nchem.2748

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