Zhou Xukai, Xu Yan, Dong Guangbin
Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United States.
The Arnold and Mabel Beckman Laboratory of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Nat Catal. 2021 Aug;4(8):703-710. doi: 10.1038/s41929-021-00661-7. Epub 2021 Aug 2.
Arene- and heteroarene-fused rings are pervasive in biologically active molecules. Direct annulation between a C─H bond on the aromatic core and a tethered alkyl moiety provides a straightforward approach to access these scaffolds; however, such a strategy is often hampered by the need of special reactive groups and/or less compatible cyclization conditions. It would be synthetically appealing if a common native functional group can be used as a handle to enable a general C─H annulation with diverse aromatic rings. Here, we show a deacylative annulation strategy for preparing a large variety of aromatic-fused rings from linear simple ketone precursors. The reaction starts with homolytic cleavage of the ketone α C─C bond via a pre-aromatic intermediate, followed by a radical-mediated dehydrogenative cyclization. Using widely available ketones as the robust radical precursors, this deconstructive approach allows streamlined assembly of complex polycyclic structures with broad functional group tolerance.
芳烃和杂芳烃稠合环在生物活性分子中普遍存在。芳香核上的C─H键与连接的烷基部分之间的直接环化提供了一种直接的方法来获得这些骨架;然而,这种策略常常受到特殊反应基团需求和/或不太兼容的环化条件的阻碍。如果一个常见的天然官能团可以用作手柄,以实现与各种芳香环的通用C─H环化,那将在合成上具有吸引力。在这里,我们展示了一种脱酰环化策略,用于从线性简单酮前体制备多种芳香稠合环。反应始于通过预芳香中间体对酮α C─C键的均裂,随后是自由基介导的脱氢环化。使用广泛可得的酮作为稳定的自由基前体,这种解构方法允许以宽泛的官能团耐受性简化复杂多环结构的组装。