Acta Chimica Sinica ›› 2021, Vol. 79 ›› Issue (12): 1477-1480.DOI: 10.6023/A21090432 Previous Articles     Next Articles



贾红绍a, 乔保坤a,*(), 江智勇b,*()   

  1. a 河南大学 河南省手性化学国际联合基地 开封 475004
    b 河南师范大学 化学化工学院 新乡 453007
  • 投稿日期:2021-09-16 发布日期:2021-11-01
  • 通讯作者: 乔保坤, 江智勇
  • 基金资助:
    国家自然科学基金(21925103); 国家自然科学基金(21901062); 河南省重点研发和推广专项(科技攻关)基金(202102310005); 中国博士后科学基金(2021M690890); 河南省博士后基金(K21045Y); 河南省高等学校重点科研项目(22A150032); 河南大学的资助

Photoredox Catalytic Radical Coupling to Access β-Fluoro α-Amino Acid Derivatives

Hongshao Jiaa, Baokun Qiaoa(), Zhiyong Jiangb()   

  1. a International S&T Cooperation Base of Chiral Chemistry, Henan University, Kaifeng 475004, Henan, China
    b School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, Henan, China
  • Received:2021-09-16 Published:2021-11-01
  • Contact: Baokun Qiao, Zhiyong Jiang
  • Supported by:
    National Natural Science Foundation of China(21925103); National Natural Science Foundation of China(21901062); Key Technologies R&D Program of Henan(202102310005); China Postdoctoral Science Foundation(2021M690890); Henan Postdoctoral Foundation(K21045Y); Key Scientific Research Projects of Henan Colleges and Universities(22A150032); Henan University

Photoredox catalysis is a practical and efficient synthetic technique that enables previously challenging or even impossible chemical transformations proceeding effectively. As one of the most prominent contribution to green chemistry, it provides a sustainable platform to the generation of high reactive radical species under mild reaction conditions. On the other hand, β-fluoro α-amino acids are significant structural units present in enzyme inhibitors, drugs and probes. Catalytic β-C(sp3)―H fluorination of α-amino acid represents a direct synthetic approach, but the harsh reaction conditions and the limited substrate scopes lead to high difficulty for these methodologies to being generalized to industrial application. Here, we report a novel and modular protocol that is via photoredox catalytic radical coupling. By using a dicyanopyrazine-derived chromophore (DPZ) as the photoredox catalyst, two readily accessible starting substrates, that are N-aryl glycine esters and α-fluoro-aryl acetic acid-derived redox-active esters (RAEs), can undergo single-electron oxidation and reduction, respectively. The resulting ester-substituted α-amino radicals and α-fluoro benzylic radicals then experience cross coupling, a highly reactive process in radical chemistry. As a result, a series of β-fluoro-α-amino acid derivatives were obtained in high yields. In this transition metal-free catalytic system, no extra oxidant or reductant is required, representing a redox neutral platform. General procedure for the synthesis of β-fluoro-α-amino acid derivatives is: to a flame dried Schlenk tube was sequentially added N-aryl substituted glycine esters 1 (0.4 mmol), RAEs 2 (0.2 mmol), DPZ (0.004 mmol, 1.42 mg), tetra-n-butyl- ammonium bromide (0.04 mmol, 12.9 mg), sodium dihydrogen phosphate (0.40 mmol, 48 mg) and cyclopentyl methyl ester (CPME) (4 mL). Then degassed three times by freeze-pump-thaw method. The reaction mixture was stirred under an argon atmosphere at 25 ℃ irradiated by a 3 W blue LED for 48 h. After completion of the reaction, the reaction mixture was directly loaded onto a short basified silica gel column, followed by gradient elution with petroleum ether/ethyl acetate (V/V, 8/1). Removing the solvent in vacuo, afforded products.

Key words: photoredox catalysis, dicyanopyrazine-derived chromophore (DPZ), radical coupling, N-aryl glycine esters, redox-active esters (RAEs), β-fluoro-α-amino acid derivatives