可见光诱导氯化铁催化苯并噁嗪-2-酮与烷烃的脱氢偶联烷基化反应

doi:10.6023/A24100329

摘要/Abstract

以价廉易得的烷烃为烷基化试剂, 发展了一种基于配体-金属电荷转移(ligand-to-metal charge transfer)机制的可见光诱导铁催化苯并噁嗪-2-酮烷基化新方法. 以氯化铁为光催化剂, 空气为氧化剂, 四丁基氯化铵为氢原子转移促进剂, 在390 nm可见光诱导下实现了苯并噁嗪-2-酮C(sp²)—H键和烷烃C(sp³)—H键之间的交叉脱氢偶联反应, 构建新的C(sp²)—C(sp³)键, 实现烷基化苯并噁嗪-2-酮衍生物的高效合成. 该方法具有反应条件绿色温和、位点选择性高、操作简单等优点, 在生物活性分子后续结构修饰中具有较高的应用价值.

关键词: 光催化, 烷烃, 苯并噁嗪-2-酮, 烷基化反应, 配体-金属电荷转移

Homogeneous visible-light photoredox catalysis has emerged as a powerful tool in modern organic synthesis, which utilizes inexhaustible light to facilitate carbon-carbon and carbon-heteroatom bond formation under eco-friendly and mild conditions. Due to the incapablity of most organic compounds to absorb visible light, homogeneous photocatalysts such as precious metals (rhodium and iridium-complexes) and elaborate organic dyes were often employed through their visible light-driven electron/energy transfer to sensitize organic molecules in photoredox catalysis. However, these photocatalysts are not conducive to large-scale production due to the relatively high cost. Iron is an ideal candidate for economical and eco-friendly catalysis because of its abundant availability and nontoxicity. Recently, iron-photocatalyzed bond formation reactions via ligand-to-metal charge transfer (LMCT) have attracted huge attention. Functionalized benzoxazin-2-ones are important N-heterocycles found in many natural products, bioactive molecules and pharmaceuticals. Among these benzoxazin-2-one derivatives, alkylated benzoxazin-2-ones have received significant attention due to their valuable biological and pharmacological activities. From a synthetic point of view, the direct C—H alkylation of benzoxazin-2-ones represents one of the most straightforward and efficient methods for producing alkylated benzoxazin-2-ones due to its high atom and step economy. Alkanes are low cost and abundant feedstock materials, which have been widely used as the alkylation reagents in organic synthesis. In the present work, we report the development of iron-catalyzed C—H alkylation of benzoxazin-2-ones with alkanes via photoinduced LMCT. With FeCl₃ as the photocatalyst, ambient air as the oxidant, tetrabutylammonium chloride as the promoter, a series of 3-alkylbenzoxazin-2-ones were efficiently synthesized under mild and eco-friendly conditions. The chlorine radical generated in situ serves as a hydrogen atom-transfer reagent. In addition, the present reaction can be smoothly scaled-up to gram level, which indicates it could be applied in industrial synthesis of pharmaceuticals.

Key words: photocatalysis, alkane, benzoxazin-2-ones, alkylation, ligand-to-metal charge transfer

引用此文

辛翠, 蒋俊, 邓紫微, 欧丽娟, 何卫民. 可见光诱导氯化铁催化苯并噁嗪-2-酮与烷烃的脱氢偶联烷基化反应[J]. 化学学报, 2024, 82(11): 1109-1113.

Cui Xin, Jun Jiang, Zi-Wei Deng, Li-Juan Ou, Wei-Min He. Photoinduced FeCl₃‑catalyzed Cross-Dehydrogenative Alkylation of Benzoxazin-2-ones with Alkanes[J]. Acta Chimica Sinica, 2024, 82(11): 1109-1113.

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图/表 7

图式1. 光催化苯并噁嗪-2-酮的烷基化反应

Scheme 1. Photoinduced C—H alkylation of benzoxazin-2-ones

Entry		Variations from the standard condition	Yield^b/%
1		None	87
2		FeCl₂, CeCl₃ or CuCl₂ was used	56, 23, 12
3		Fe(acac)₃, Fe(NO₃)₃ or Fe₂(SO₄)₃ was used	14, 19, 71
4		TBABr or LiCl was used	51, 68
5		DCM, THF, DMSO or DMF was used	all trace
6		455 nm LED or 520 nm LED was used	15, 21
7		455 nm LED (5 W) was used	52
8		O₂ was used	84
9	N₂ was used		N.R.
10	Without catalyst, TBACl or light		N.R.

表1. 反应条件筛选a

Table 1. Optimization of reaction conditionsa

表2. 3-烷基苯并噁嗪-2-酮范围

Table 2. Scope of C3-alkyl benzoxazin-2-ones

图式2. 克级合成3aa

Scheme 2. Gram-scale synthesis of 3aa

图式3. 控制实验

Scheme 3. Control experiments

图1. 灯光开/关实验

Figure 1. Light on/off experiment

图式4. 可能的反应机理

Scheme 4. Proposed mechanism

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