摘要
本研究开发了一种无催化剂、可见光驱动的电子供体-受体(EDA)复合物策略,实现了N-芳基丙烯酰胺的分子内氢芳基化反应,高效构建吲哚酮骨架.该策略无需外加光催化剂、酸或氧化剂.机理研究表明:在弱碱条件(Cs_(2)CO_(3))下,二苯基二硫醚(Ph SSPh)水解生成的苯硫酚阴离子(PhS^(-))作为电子供体,与N-芳基丙烯酰胺底物形成光活性EDA复合物.紫外-可见光谱实验证实其在450~500 nm的特征吸收,为吲哚酮衍生物的绿色合成提供了一条新途径.
This work presents a catalyst-free,visible-light-driven protocol for constructing biologically relevant oxindoles via intramolecular hydroarylation of N-arylacrylamides,mediated by in situ-generated electron donor-acceptor(EDA)complexes.Diverging from conventional transition-metal catalysis or oxidative cyclization,which require metal pre-catalysts,pre-functionalized substrates,or strong oxidants,this strategy operates without external photocatalysts,acids,or chemical oxidants.Central to the mechanism is the weak base(Cs_(2)CO_(3))-promoted hydrolysis of diphenyl disulfide(PhSSPh),which generates phenylthiolate anions(PhS^(-))as potent electron donors.Mechanistic studies,including comprehensive UV-Vis spectroscopy,establish that these PhS-anions form a photoactive EDA complex with electron-deficient N-arylacrylamides(acceptors).Critically,this complex exhibits a distinct broad absorption band(450~500 nm),enabling direct visible-light irradiation(455~460 nm)to trigger single-electron transfer(SET)and initiate radical cyclization.Deuterium-labeling experiments(D_(2)O)confirm that trace water serves as the proton source in the reaction,while radical trapping studies corroborate the radical nature of the pathway.Substrate scope evaluation(33 diverse examples)demonstrates broad functional group tolerance on the aryl ring,accommodating both electron-donating(para-methyl,para-methoxy)and electron-withdrawing(para-halogen,trifluoromethyl,cyano,ester)substituents,as well as heterocyclic motifs(pyridyl).Ortho-substituted arenes cyclize with reduced efficiency due to steric hindrance,while meta-methyl substitution yieldsα/β-regioisomers.Diverse N-alkyl groups(isopropyl,cyclohexyl),functionalized N-substituents(benzyl,ester),and conformationally constrained diamides are compatible,highlighting versatility.A key limitation is the inactivity of free N-H acrylamides under the current conditions,suggesting the N-substituent is crucial for EDA complex formation or reactivity.Significant advantages of this strategy include operational simplicity(ambient temperature,16 h reaction time),avoidance of precious metals and stoichiometric oxidants,demonstrated gram-scale feasibility,and the utilization of benign visible light.By leveraging the unique electron-donating capability of in situ-generated sulfur anions(PhS^(-))to form catalytically active EDA complexes,this work provides a green,practical,and mechanistically distinct route to privileged oxindole scaffolds.
作者
雷平
苏秦
王栋
Shahid Ali Khan
阿布拉江·克依木
Lei Ping;Su Qin;Wang Dong;Shahid Ali Khan;Ablajan Keyume(State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources,College of Chemistry,Xinjiang University,Urumqi 830017,China;Department of Chemistry,School of Natural Sciences,National University of Sciences and Technology,Islamabad 44000,Pakistan)
出处
《化学学报》
北大核心
2025年第11期1379-1385,共7页
Acta Chimica Sinica
基金
上海合作组织科技伙伴计划(No.2022E01049)
国家自然科学基金(No.21961038)资助项目。
