Visible light-mediated radical fluoromethylation via halogen atom transfer activation of fluoroiodomethane.
Visible light-mediated radical fluoromethylation via halogen atom transfer activation of fluoroiodomethane.
复制标题
氟碘甲烷的卤素原子转移活化可见光介导的自由基氟甲基化反应。
DOI：
10.1039/d1sc04554g
复制
发表时间：
2021-10-06
期刊：
影响因子：
8.4
通讯作者：
Gaunt MJ
中科院分区：
文献类型：
--
作者：
Deneny PJ;Kumar R;Gaunt MJ
引入氟甲基基团可以深刻地影响有机分子的物理化学性质，为发现新的药物制剂提供了一个有前途的策略。未官能化的C（sp2）中心的直接氟甲基化可以使用氟甲基自由基来实现，但是目前用于它们的生成的方法通常依赖于经由低效的单电子转移途径活化非商业或昂贵的自由基前体，这限制了它们的合成应用。在这里，我们报告的氟甲基化战略的基础上，从市售的氟碘甲烷通过卤素原子转移的氟甲基自由基的生成的发展。这种活化模式由可见光和三（三甲基甲硅烷基）硅烷协调，三（三甲基甲硅烷基）硅烷作为氢原子和卤素原子转移试剂，以促进通过自由基链过程形成C（sp3）-CH2F键。这种无金属和光催化剂的转化的效用通过多组分合成复杂的α-氟甲基胺和氨基酸衍生物通过自由基加成原位形成的亚胺离子，和β-氟甲基酯和酰胺的建设从缺电子烯烃受体证明。这些复杂的氟甲基化产物，其中许多是无法通过以前报道的方法，可以作为有用的积木或片段在学术界和工业界的合成和药物化学。通过可见光介导的卤原子转移活化氟碘甲烷生成氟甲基自由基促进了α-氟甲基胺的多组分合成和缺电子烯烃的氢氟甲基化。
Incorporation of the fluoromethyl group can profoundly influence the physicochemical properties of organic molecules, offering a promising strategy for the discovery of novel pharmaceutical agents. Direct fluoromethylation of unfunctionalized C(sp2) centres can be achieved using fluoromethyl radicals, but current methods for their generation usually rely on the activation of non-commercial or expensive radical precursors via inefficient single electron transfer pathways, which limits their synthetic application. Here we report the development of a fluoromethylation strategy based on the generation of fluoromethyl radicals from commercially available fluoroiodomethane via halogen atom transfer. This mode of activation is orchestrated by visible light and tris(trimethylsilyl)silane, which serves as both a hydrogen- and halogen atom transfer reagent to facilitate the formation of C(sp3)–CH2F bonds via a radical chain process. The utility of this metal- and photocatalyst-free transformation is demonstrated through the multicomponent synthesis of complex α-fluoromethyl amines and amino acid derivatives via radical addition to in situ-formed iminium ions, and the construction of β-fluoromethyl esters and amides from electron-deficient alkene acceptors. These complex fluoromethylated products, many of which are inaccessible via previously reported methods, may serve as useful building blocks or fragments in synthetic and medicinal chemistry both in academia and industry. Generation of fluoromethyl radicals via visible light-mediated halogen atom transfer activation of fluoroiodomethane facilitates both the multicomponent synthesis of α-fluoromethyl amines and the hydrofluoromethylation of electron-deficient alkenes.
登录
查看更多内容
影响因子：
16.6
作者：
Lingel, Andreas;Vulpetti, Anna;Frank, Andreas O.
通讯作者：
Frank, Andreas O.
影响因子：
7.3
作者：
Gillis, Eric P.;Eastman, Kyle J.;Meanwell, Nicholas A.
通讯作者：
Meanwell, Nicholas A.
影响因子：
64.8
作者：
KOLLONITSCH, J;PATCHETT, AA;ASTER, SD
通讯作者：
ASTER, SD
影响因子：
8.4
作者：
Hell SM;Meyer CF;Ortalli S;Sap JBI;Chen X;Gouverneur V
通讯作者：
Gouverneur V
DOI：
10.1126/science.aat4133
发表时间：
2018-06-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Le C;Chen TQ;Liang T;Zhang P;MacMillan DWC
通讯作者：
MacMillan DWC