Zhang Linghong, You Mengdi, Ban Xu, Zhao Xiaowei, Yin Yanli, Cao Shanshan, Jiang Zhiyong
Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University Kaifeng Henan P. R. China 475004
School of Chemistry and Chemical Engineering, Pingyuan Laboratory, Henan Normal University Xinxiang Henan P. R. China 453007
Chem Sci. 2024 May 7;15(23):8828-8834. doi: 10.1039/d4sc00748d. eCollection 2024 Jun 12.
The dearomative expansion of aromatic rings has long been pursued by chemists due to its potential to provide tractable approaches for synthesizing valuable non-aromatic molecules. To circumvent the conventional use of hazardous and unstable diazo compounds, photochemical synthesis has recently emerged as a promising platform. However, protocols that can effectively handle both arenes and azaarenes remain scarce. Herein, we introduce a generic strategy that efficiently converts β-(aza)aryl-β-substituted enones into biologically significant cycloheptatriene derivatives, including their aza-variants. This method allows for the easy modulation of diverse functional groups on the product and demonstrates a wide substrate scope, evidenced by its excellent tolerance to various drug motifs and good compatibility with five-membered azaarenes undergoing ring expansion. Moreover, DFT calculations of plausible mechanisms have motivated the implementation of an important cascade diradical recombination strategy for 1,3-dienones, thus facilitating the synthesis of valuable 2-oxabicyclo[3.1.0]hex-3-ene derivatives.
长期以来,化学家们一直致力于芳香环的去芳构化扩展,因为它有可能为合成有价值的非芳香族分子提供易于处理的方法。为了避免传统上使用危险且不稳定的重氮化合物,光化学合成最近已成为一个有前景的平台。然而,能够有效处理芳烃和氮杂芳烃的方案仍然很少。在此,我们介绍一种通用策略,该策略能有效地将β-(氮杂)芳基-β-取代的烯酮转化为具有生物学意义的环庚三烯衍生物,包括它们的氮杂变体。该方法允许对产物上的各种官能团进行轻松调节,并展示了广泛的底物范围,这体现在它对各种药物基团具有出色的耐受性,以及与进行环扩展的五元氮杂芳烃具有良好的兼容性。此外,对合理机理的密度泛函理论(DFT)计算推动了对1,3 - 二烯酮实施重要的级联双自由基重组策略,从而促进了有价值的2 - 氧杂双环[3.1.0]己 - 3 - 烯衍生物的合成。