Huang Jiahui, You Yuantao, Ma Yijian, He Xingying, Li Yixiao, Kesavan Arunachalam, Jin Chengzhi, Shen Chengshuo, Zhang Min, Yuan Kedong
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
School of Chemistry and Chemical Engineering, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, 310018, China.
Adv Sci (Weinh). 2025 Apr 28:e2500897. doi: 10.1002/advs.202500897.
Transition-metal-catalyzed transformations offer a powerful approach to rapidly synthesize complex benzo-fused heterocycles, crucial for drug and material development. However, existing synthetic strategies face challenges such as limited functional group compatibility, reliance on complex ligands, and difficulties in controlling chemoselectivity with prefunctionalized substrates. Herein, a ligand-free Pd(II)/Cu(I) catalytic system is presented that facilitates reactions between arylsulfonyl chlorides and unactivated olefins under mild conditions, enabling the efficient synthesis of saturated benzo-fused six-membered heterocycles. This streamlined strategy employs dual Csp─Csp bond formation, producing diverse N/O-polyheterocycles and allowing late-stage functionalization of bioactive molecules with excellent yields and high chemoselectivity. The key to the success of this reaction is the formation of high-valent Ar-Pd(III) intermediate, which drives the reaction through 1,2-Pd migration and electrophilic C─H arylation. This unique reactivity pathway facilitates the formation of benzo-fused heterocycles while effectively avoiding the β-H elimination typically associated with Heck-type reactions.
过渡金属催化的转化反应为快速合成复杂的苯并稠合杂环提供了一种强有力的方法，这对于药物和材料开发至关重要。然而，现有的合成策略面临着诸如官能团兼容性有限、依赖复杂配体以及难以控制预官能化底物的化学选择性等挑战。在此，我们展示了一种无配体的Pd(II)/Cu(I)催化体系，该体系能在温和条件下促进芳基磺酰氯与未活化烯烃之间的反应，从而实现饱和苯并稠合六元杂环的高效合成。这种简化的策略采用了双重Csp─Csp键形成，可生成多种N/O-多杂环，并能以优异的产率和高化学选择性实现生物活性分子的后期官能化。该反应成功的关键在于高价Ar-Pd(III)中间体的形成，它通过1,2-Pd迁移和亲电C─H芳基化驱动反应。这种独特的反应途径有助于苯并稠合杂环的形成，同时有效避免了通常与Heck型反应相关的β-H消除。
