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Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N–Aryl Azacycle Photomediated Ring Contractions

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    Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N–Aryl Azacycle Photomediated Ring Contractions
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2024, 146, 8, 5580–5596
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    https://doi.org/10.1021/jacs.3c13982
    Published February 12, 2024
    Copyright © 2024 American Chemical Society
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    Abstract

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    Under mild blue-light irradiation, α-acylated saturated heterocycles undergo a photomediated one-atom ring contraction that extrudes a heteroatom from the cyclic core. However, for nitrogenous heterocycles, this powerful skeletal edit has been limited to substrates bearing electron-withdrawing substituents on nitrogen. Moreover, the mechanism and wavelength-dependent efficiency of this transformation have remained unclear. In this work, we increased the electron richness of nitrogen in saturated azacycles to improve light absorption and strengthen critical intramolecular hydrogen bonding while enabling the direct installation of the photoreactive handle. As a result, a broadly expanded substrate scope, including underexplored electron-rich substrates and previously unsuccessful heterocycles, has now been achieved. The significantly improved yields and diastereoselectivities have facilitated reaction rate, kinetic isotope effect (KIE), and quenching studies, in addition to the determination of quantum yields. Guided by these studies, we propose a revised ET/PT mechanism for the ring contraction, which is additionally corroborated by computational characterization of the lowest-energy excited states of α-acylated substrates through time-dependent DFT. The efficiency of the ring contraction at wavelengths longer than those strongly absorbed by the substrates was investigated through wavelength-dependent rate measurements, which revealed a red shift of the photochemical action plot relative to substrate absorbance. The elucidated mechanistic and photophysical details effectively rationalize empirical observations, including additive effects, that were previously poorly understood. Our findings not only demonstrate enhanced synthetic utility of the photomediated ring contraction and shed light on mechanistic details but may also offer valuable guidance for understanding wavelength-dependent reactivity for related photochemical systems.

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.3c13982.

    • Experimental procedures, optimization, characterization data, NMR spectra for all compounds, UV–Vis data, kinetic experiments, quantum yield determination, model of inner filter effect on rate, crystallographic data, computational details, and Cartesian coordinates of DFT-optimized structures (PDF)

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    CCDC 2309251–2309255 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing [email protected], or by contacting The Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax: + 44 1223 336033.

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    This article is cited by 12 publications.

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    12. Yi Peng, Guoqiang Wang, Hendrik F. T. Klare, Martin Oestreich. Ring Contraction of Saturated Cyclic Amines and Rearrangement of Acyclic Amines Through Their Corresponding Hydroxylamines. Angewandte Chemie International Edition 2024, 63 (40) https://doi.org/10.1002/anie.202410483
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2024, 146, 8, 5580–5596
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.3c13982
    Published February 12, 2024
    Copyright © 2024 American Chemical Society
    Request reuse permissions

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