摘要
通过可见光驱动光氧化还原催化,发展了一种新颖、便利的β-氟代-α-氨基酸衍生物的合成方法.以非金属的二氰基吡嗪衍生物(DPZ)为光催化剂,以易于制备的N-芳基甘氨酸酯和芳基乙酸氧化还原酯为原料,通过单电子氧化还原分别生成酯基取代α-氨烷基自由基及α-氟代苄基自由基.经过高反应活性自由基的交叉偶联,高产率地得到目标产物.该方法由于氧化还原中性反应途径而无需额外的氧化剂或还原剂,且属于绿色、可持续的有机催化合成策略.
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-fluoroα-amino acids are significant structural units present in enzyme inhibitors,drugs and probes.Catalyticβ-C(sp^(3))―H fluorination ofα-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 andα-fluoro-aryl acetic acid-derived redox-active esters(RAEs),can undergo single-electron oxidation and reduction,respectively.The resulting ester-substitutedα-amino radicals andα-fluoro benzylic radicals then experience cross coupling,a highly reactive process in radical chemistry.As a result,a series ofβ-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 ofβ-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-butylammonium 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.
作者
贾红绍
乔保坤
江智勇
Hongshao Jia;Baokun Qiao;Zhiyong Jiang(International S&T Cooperation Base of Chiral Chemistry,Henan University,Kaifeng 475004,Henan,China;School of Chemistry and Chemical Engineering,Henan Normal University,Xinxiang 453007,Henan,China)
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2021年第12期1477-1480,共4页
Acta Chimica Sinica
基金
国家自然科学基金(Nos.21925103,21901062)
河南省重点研发和推广专项(科技攻关)基金(No.202102310005)
中国博士后科学基金(No.2021M690890)
河南省博士后基金(No.K21045Y)
河南省高等学校重点科研项目(No.22A150032)
河南大学的资助.
作者简介
乔保坤,E-mail:qiaobaok@163.com;江智勇,E-mail:jiangzhiyong@htu.edu.cn
