Kim Sojung F, Schwarz Henrik, Jurczyk Justin, Nebgen Bailey R, Hendricks Hailey, Park Hojoon, Radosevich Andrew, Zuerch Michael W, Harper Kaid, Lux Michaelyn C, Yeung Charles S, Sarpong Richmond
Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, United States.
Lawrence Berkeley National Laboratory, Materials Sciences Division, Berkeley, California 94720, United States.
J Am Chem Soc. 2024 Feb 28;146(8):5580-5596. doi: 10.1021/jacs.3c13982. Epub 2024 Feb 12.
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.
在温和的蓝光照射下，α-酰化饱和杂环会发生光介导的单原子环收缩反应，从环状核心挤出一个杂原子。然而，对于含氮杂环，这种强大的骨架编辑仅限于氮上带有吸电子取代基的底物。此外，这种转化的机理和波长依赖性效率仍不清楚。在这项工作中，我们提高了饱和氮杂环中氮的电子丰富度，以改善光吸收并加强关键的分子内氢键，同时实现光反应性手柄的直接安装。结果，现在已经实现了广泛扩展的底物范围，包括未充分探索的富电子底物和以前未成功的杂环。显著提高的产率和非对映选择性促进了反应速率、动力学同位素效应（KIE）和猝灭研究，此外还测定了量子产率。在这些研究的指导下，我们提出了一种修订的电子转移/质子转移（ET/PT）环收缩机理，通过含时密度泛函理论（TD-DFT）对α-酰化底物最低能量激发态的计算表征进一步证实了这一机理。通过波长依赖性速率测量研究了在比底物强烈吸收的波长更长的波长下环收缩的效率，结果表明光化学作用曲线相对于底物吸光度发生了红移。阐明的机理和光物理细节有效地解释了以前理解不足的经验观察结果，包括加和效应。我们的发现不仅证明了光介导环收缩的合成效用增强，并揭示了机理细节，还可能为理解相关光化学系统的波长依赖性反应性提供有价值的指导。
