Zhou Chao, Stepanova Elena V, Shatskiy Andrey, Kärkäs Markus D, Dinér Peter
Department of Chemistry, KTH Royal Institute of Technology, Stockholm, Sweden.
Research School of Chemistry & Applied Biomedical Sciences, Tomsk Polytechnic University, Tomsk, Russia.
Nat Commun. 2025 Apr 16;16(1):3610. doi: 10.1038/s41467-025-58808-0.
Aromatic compounds serve as key feedstocks in the chemical industry, typically undergoing functionalization or full reduction. However, partial reduction via dearomative sequences remains underexplored despite its potential to rapidly generate complex three-dimensional scaffolds and the existing dearomative strategies often require metal-mediated multistep processes or suffer from limited applicability. Herein, a photocatalytic radical cascade approach enabling dearomative difunctionalization through selective spirocyclization/imination of nonactivated arenes is reported. The method employs bifunctional oxime esters and carbonates to introduce multiple functional groups in a single step, forming spirocyclic motifs and iminyl functionalities via N-O bond cleavage, hydrogen-atom transfer, radical addition, spirocyclization, and radical-radical cross-coupling. The reaction constructs up to four bonds (C-O, C-C, C-N) from simple starting materials. Its broad applicability is demonstrated on various substrates, including pharmaceuticals, and it is compatible with scale-up under flow conditions, offering a streamlined approach to synthesizing highly decorated three-dimensional frameworks.
芳香族化合物是化学工业中的关键原料，通常会进行官能化或完全还原。然而，尽管通过去芳构化序列进行部分还原具有快速生成复杂三维支架的潜力，但该领域仍未得到充分探索，并且现有的去芳构化策略通常需要金属介导的多步过程，或者适用性有限。在此，报道了一种光催化自由基级联方法，该方法通过非活化芳烃的选择性螺环化/亚胺化实现去芳构化双官能化。该方法使用双官能肟酯和碳酸酯在一步中引入多个官能团，通过N-O键裂解、氢原子转移、自由基加成、螺环化和自由基-自由基交叉偶联形成螺环基序和亚胺基官能团。该反应从简单的起始原料构建多达四个键（C-O、C-C、C-N）。其在包括药物在内的各种底物上都具有广泛的适用性，并且与流动条件下的放大反应兼容，为合成高度修饰的三维骨架提供了一种简化的方法。
