Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Korea.
J Am Chem Soc. 2023 Jun 7;145(22):12214-12223. doi: 10.1021/jacs.3c02314. Epub 2023 May 24.
Simple aromatic compounds like benzene are abundant feedstocks, for which the preparation of derivatives chiefly begins with electrophilic substitution reactions or, less frequently, reductions. Their high stability makes them particularly reluctant to participate in cycloadditions under ordinary reaction conditions. Here, we demonstrate the exceptional ability of 1,3-diaza-2-azoniaallene cations to undergo formal (3 + 2) cycloadditions with unactivated benzene derivatives below room temperature, providing thermally stable dearomatized adducts on a multi-gram scale. The cycloaddition, which tolerates polar functional groups, activates the ring toward further elaboration. On treatment with dienophiles, the cycloadducts undergo a (4 + 2) cycloaddition-cycloreversion cascade to yield substituted or fused arenes, including naphthalene derivatives. The overall sequence results in the transmutation of arenes through an exchange of the ring carbons: a two-carbon fragment from the original aromatic ring is replaced with another from the incoming dienophile, introducing an unconventional disconnection for the synthesis of ubiquitous aromatic building blocks. Applications of this two-step sequence to the preparation of substituted acenes, isotopically labeled molecules, and medicinally relevant compounds are demonstrated.
简单的芳香族化合物，如苯，是丰富的原料，其衍生物的制备主要从亲电取代反应开始，或者较少见的还原反应。它们的高稳定性使得它们在普通反应条件下特别不愿意参与环加成反应。在这里，我们证明了 1,3-二氮杂-2-氮烯阳离子具有非凡的能力，可在室温以下与未活化的苯衍生物进行形式上的（3 + 2）环加成反应，以多克规模提供热稳定的去芳构化加合物。该环加成反应可容忍极性官能团，并使环活化以进一步进行修饰。用双烯亲合物处理时，环加成物会经历（4 + 2）环加成-环重排级联反应，生成取代或稠合的芳烃，包括萘衍生物。整个序列导致芳烃通过环碳原子的交换发生嬗变：原始芳环中的两个碳原子片段被另一个来自亲双烯体的片段取代，为合成无处不在的芳烃构建块引入了一种非常规的断键。该两步序列的应用已展示于取代的并苯、同位素标记分子和具有医学相关性的化合物的制备中。
