CIQTEK EPR Facilitates Efficient Synthesis of Benzofuran Derivatives Methods

Recently, Zhichao Jin's research team at Guizhou University has demonstrated that heteroatomic anions can be used as super-electron donors to initiate free-radical reactions to easily synthesize 3-substituted benzofurans. The resulting products have broad application prospects in organic synthesis and pesticide development.

The results were published in the prestigious journal Nature Communications under the title "Facile access to benzofuran derivatives through radical reactions with heteroatom-centered super-electron-donors". In the study, CIQTEK's X-band continuous-wave electron paramagnetic resonance spectrometer EPR200-Plus was used to confirm the generation of free radical species in the reaction system.

Benzofurans are among the 100 major cyclic structures widely found in human clinical drugs. In particular, 3-substituted benzofurans are frequently found as core structures in many natural and non-natural drug molecules with proven biological activity. In order to obtain 3-substituted benzofuran derivatives with a wide range of functionalities rapidly and selectively, the development of new and efficient synthetic methods is essential. Single-electron transfer reaction is one of the most efficient ways to construct functionalized 3-substituted benzofurans, and a suitable electron donor is crucial for the success of the single-electron transfer process. However, to date, no study has reported the use of heteroatom-centered anions as direct super-electron donors for single-electron transfer reactions.

The research team of Zhichao Jin at Guizhou University has easily synthesized 3-substituted benzofuran molecules with various heteroatom functionalities by utilizing heteroatom anions as SEDs to initiate the free radical reactions in their studies. Phosphines, thiols, and anilines with different substitution patterns performed well in this intermolecular free radical coupling reaction, and the 3-substituted benzofuran products with heteroatom functionalities showed moderate to excellent yields.

Fig. 1 | Bioactivities, syntheses of 3-substituted benzofurans and SEDs for radical reactions. a Commercial drugs containing 3-substituted benzofuran structures. b Typical methods for access to 3-substituted benzofurans. c Representative organic small molecular SEDs. d Heteroatom anions as SEDs for 3-heteroalkylbenzofuran synthesis.

The generation of free radical species in the reaction system was confirmed in the study using EPR technique (CIQTEK EPR200-Plus). The EPR spectra of the mixture of 1a, HPPh2 and LDA in 25°C DME showed a signal similar to the phenyl g factor at g = 2.0023.

Fig. 4 | EPR spectrum of the reaction mixtures and control experiments. a EPR spectrum of the reaction mixtures. b Feasibilities of the heteroatomic anions as SEDs for the radical reactions. c Cross-radical coupling reactions with mercaptans. d The X-band EPR spectrum of 1:2:2 stoichiometric reaction of 1a (0.1 mmol), HPPh2 (0.2 mmol), and LDA (0.2 mmol) was measured at 298 K with DME (2 mL) as solvent at a microwave frequency of 9.418333054 GHz (g = 2.0023).

Summary

Nature Communications：Facile access to benzofuran derivatives through radical reactions with heteroatom-centered super-electron-donors

The development of suitable electron donors is critical to single-electron-transfer (SET) processes. The use of heteroatom-centered anions as superelectron-donors (SEDs) for direct SET reactions has rarely been studied. Here we show that heteroatom anions can be applied as SEDs to initiate radical reactions for facile synthesis of 3-substituted benzofurans. Phosphines, thiols and anilines bearing different substitution patterns work well in this inter-molecular radical coupling reaction and the 3-functionalized benzofuran products bearing heteroatomic functionalities are given in moderate to excellent yields. The reaction mechanism is elucidated via control experiments and computational methods. The afforded products show promising applications in both organic synthesis and pesticide development.

CIQTEK Electron Paramagnetic Resonance

CIQTEK has launched a full series of commercialized X-band electron paramagnetic resonance spectrometers with core intellectual property rights: X-band pulsed electron paramagnetic resonance spectrometer EPR100, X-band continuous-wave electron paramagnetic resonance spectrometer EPR200-Plus, and tabletop electron paramagnetic resonance spectrometer EPR200M; and W-band pulsed electron paramagnetic resonance spectrometer EPR-W900. EPR-W900 has important and wide applications in chemical, environmental, material physics, biomedical, food and industrial fields.

CIQTEK Electron Paramagnetic Resonance Spectrometer