Photocatalytic In Situ Amination of the Migrating Aryl Group: Rapid Access to 4‑Aminated Benzenepropanamides

Aryl migration-induced difunctionalization of alkenes is a fascinating strategy for increasing the molecular complexity via the simultaneous formation of two chemical bonds across the C–C double bond. Despite the significant advances in this area, the in situ functionalization of the migrating aryl ring remains elusive due to the incompatibility between the conventional arene C–H functionalization strategy and the aryl migration process. Herein, we disclose the photocatalytic in situ amination of the migrating aryl ring in which an aryl ring is aminated and migrated within a single step, providing rapid access to valuable 4-aminated benzenepropanamide scaffolds. Such transformations enable the formation of an additional chemical bond on the migrating aryl ring beyond those two formed on the alkene carbons, significantly increasing the flexibility of the aryl migration strategy and improving the migration efficiency for the aminated aryl ring. The energy transfer catalytic cycle between the photosensitizer and the bifunctional reagents plays a pivotal role in combining the aryl migration process with the emerging radical-based arene remote C–H amination step. Experimental mechanistic studies support the proposed reaction pathway. The power of this protocol was demonstrated by the functionalization of pharmaceutically relevant molecules, the efficient synthesis of bioactive molecule analogs, and antibacterial activity investigations.

芳基迁移诱导的烯烃双官能团化反应是一种极具吸引力的策略，可通过在碳碳双键上同时构建两个化学键来提升分子复杂度。尽管该领域已取得诸多重要进展，但由于传统芳烃C-H官能团化策略与芳基迁移过程存在兼容性问题，迁移芳环的原位官能团化仍极具挑战性。本文中，我们报道了迁移芳环的光催化原位氨基化反应：芳环在单一步骤中同时完成氨基化与迁移，可快速获得具有应用价值的4-氨基苯丙酰胺骨架。该类反应可在迁移芳环上构建除烯烃双键两端所形成的两个化学键之外的额外化学键，显著提升了芳基迁移策略的灵活性，并改善了氨基化芳环的迁移效率。光敏剂与双功能试剂之间的能量转移催化循环，在将芳基迁移过程与新兴的基于自由基的芳烃远程C-H氨基化步骤相结合的过程中发挥了关键作用。实验机理研究验证了本文提出的反应路径。该合成方法的实用性可通过药物相关分子的官能团化、生物活性分子类似物的高效合成以及抗菌活性研究得到充分展示。