Laboratory for Computational Molecular Design, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
National Center for Competence in Research─Catalysis (NCCR-Catalysis), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
J Org Chem. 2022 Jul 15;87(14):8849-8857. doi: 10.1021/acs.joc.1c02991. Epub 2022 Jun 28.
A highly appealing strategy to modulate a catalyst's activity and/or selectivity in a dynamic and noninvasive way is to incorporate a photoresponsive unit into a catalytically competent molecule. However, the description of the photoinduced conformational or structural changes that alter the catalyst's intrinsic reactivity is often reduced to a handful of intuitive static representations, which can struggle to capture the complexity of flexible organocatalysts. Here, we show how a comprehensive exploration of the free energy landscape of N-alkylated azobenzene-tethered piperidine catalysts is essential to unravel the conformational characteristics of each configurational state and explain the experimentally observed reactivity trends. Mapping the catalysts' conformational space highlights the existence of false ON or OFF states that lower their switching ability. Our findings expose the challenges associated with the realization of a reversible steric shielding for the photocontrol of Brønsted basicity of piperidine photoswitchable organocatalysts.
将光响应单元引入催化活性分子中，是一种在动态和非侵入性条件下调节催化剂活性和/或选择性的极具吸引力的策略。然而，对改变催化剂固有反应性的光诱导构象或结构变化的描述往往简化为少数直观的静态表示形式，这可能难以捕捉柔性有机催化剂的复杂性。在这里，我们展示了如何全面探索 N-烷基化偶氮苯连接的哌啶催化剂的自由能景观，这对于揭示每个构象状态的构象特征并解释实验观察到的反应性趋势至关重要。绘制催化剂的构象空间图突出了存在错误的“开”或“关”状态，这降低了它们的切换能力。我们的研究结果揭示了在实现可逆位阻屏蔽以光控哌啶光开关有机催化剂的布朗斯台德碱性方面所面临的挑战。
