摘要
报道了一种在可见光诱导下,利用芳香酸酐的酰基自由基与α-三氟甲基烯烃进行二氟烯基化的新策略.该方法以廉价易得的芳香酸酐为酰基源,在温和条件下通过蓝光照射实现酰基自由基的原位生成,展现出优异的官能团兼容性和宽泛的底物普适性(32个实例,最高产率82%).另外,酸酐上取代基的电子性质(吸电子基团促进C—O键断裂)和空间位阻(影响区域选择性)是调控反应选择性的关键因素.机理研究表明,可见光引发的单电子转移在自由基链的激活中起关键作用,并通过自由基/极性交叉过程成功构建了γ,γ-二氟烯丙基酮.放大试验和后修饰验证了该方法的实用性,预示其在有机合成中具有广阔的应用前景.
Fluorine-containing organic molecules offer beneficial biological activity,lipophilicity,and metabolic stability.Among these,gem-difluoroalkenes are known for their distinctive structures and wide-ranging uses in biology,medicine,and agriculture.As important synthetic building blocks,converting them into various functionalized compounds attracts significant scientific interest.Recent progress has focused on innovative methods for synthesizing gem-difluoroalkenes,especially through C—F bond activation ofα-trifluoromethyl alkenes.This study introduces a new defluorinative difluoroalkenylation reaction that uses acyl radicals from readily available,cost-effective aromatic carboxylic anhydrides.Under visible-light irradiation,these anhydrides react withα-trifluoromethyl alkenes to produceγ,γ-difluoroallylic ketones.The optimized procedure employs 4CzIPN as the photocatalyst,Cs₂CO₃as the base,PPh₃as the reductant,and N,N-dimethylformamide(DMF)as the solvent,with blue light emitting diode(LED)light.This gentle,in situ formation of acyl radicals shows excellent tolerance for various functional groups and works with a broad range of substrates(32 examples,up to 82%yield).Additionally,mechanistic studies show that the electronic and steric properties of substituents on asymmetric anhydrides influence selectivity;electron-withdrawing groups promote C—O bond cleavage,while steric hindrance determines regioselectivity.Importantly,this method avoids the use of transition metals and ligands,reducing steps and costs.Scale-up experiments confirmed its potential for practical applications,including late-stage functionalization.Mechanistic insights suggest visible-light-induced single-electron transfer in radical chain activation and a radical/polar crossover process.This straightforward and eco-friendly approach efficiently synthesizesγ,γ-difluoroallylic ketones by breaking C—O and C—F bonds.
作者
苏秦
雷平
王栋
Shahid Ali Khan
阿布拉江·克依木
Su Qin;Lei Ping;Wang Dong;Shahid Ali Khan;Ablajan Keyume(Key Laboratory of Chemistry and Utilization of Carbon based Energy Resources,College of Chemistry,Xinjiang University,Urumqi 830017,China;School of Natural Sciences,National University of Science and Technology,Islamabad 44000,Pakistan)
出处
《化学学报》
北大核心
2025年第11期1372-1378,共7页
Acta Chimica Sinica
基金
上海合作组织科技伙伴计划(No.2022E01049)
新疆维吾尔自治区自然科学基金(No.2022D01C381)资助项目。
关键词
可见光诱导
α-三氟甲基烯烃
酸酐
β-氟消除
脱氟酰化
γ
γ-二氟烯丙基酮
visible-light-induced
α-trifluoromethyl alkenes
anhydrides
β-fluorine eliminating
defluorinative acylation
γ,γ-difluoroallylic ketones
