3-羟基色酮的不对称Michael加成反应  

Asymmetric Michael Addition Reaction of 3-Hydroxychromone

作　　者：黄敏 李文哲 李敏[1,2] 张晓梅 HUANG Min;LI Wenzhe;LI Min;ZHANG Xiaomei(Chengdu Institute of Organic Chemistry,Chinese Academy of Sciences,Chengdu 610041,China;University of Chinese Academy of Sciences,Beijing 100049,China;Department of Chemistry,Xihua University,Chengdu 610039,China)

机构地区：[1]中国科学院成都有机化学研究所,四川成都610041 [2]中国科学院大学,北京100049 [3]西华大学化学系,四川成都610039

出　　处：《合成化学》2024年第9期769-778,786,共11页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21672208)。

摘　　要：3-羟基色酮骨架存在于大量天然产物中,其衍生物多具有重要的生理活性和潜在的药用价值,但目前对3-羟基色酮的不对称手性催化反应研究较少。为丰富3-羟基色酮的研究多样性,通过控制变量法对手性金鸡纳碱类催化剂、溶剂、温度、投料比、底物浓度和催化剂用量进行筛选,确定了最佳的反应条件:以化合物1a和2a的反应为例,0.10 mmol的化合物1a与0.12 mmol的化合物2a在Cat*5(10%,物质的量分数)的催化下,在1.0 mL的甲基叔丁基醚(MTBE)中于0℃下反应24~48 h。对底物进行普适性研究,以中等至优异的收率(71%~99%)和较好的对映选择性(56%~89%)获得了2-芳基3-羟基色酮衍生物。将对映选择性最高的产物3al(89%)进行30倍放大反应,能够以99%的收率和76%的对映选择性获得目标产物。所有化合物的结构经1H NMR,13C NMR, HPLC以及HR-MS(ESI)确证。3-Hydroxychromone skeleton exists in a large number of natural products,and most of its derivatives have important physiological activities and potential medicinal value.However,the asymmetric chiral catalytic reaction of 3-hydroxychromone has been studied less so far.The optimal reaction conditions were determined by screening the chiral cinchona base catalyst,solvent,temperature,ratio,concentration and catalyst load by controlled variable method:The asymmetric Michael addition reaction between 3-hydroxychromone and(E)-(2-nitrovinyl)benzene occurred at 0℃under the action of chiral cinchona base trihydrogen-bonded thiourea catalyst with methyl tert-butyl ether as the solvent.2-Aryl-3-hydroxychromone derivatives were obtained with medium to excellent yield(71%~99%yield)and good enantioselectivity(56%~89%ee).The structures of all compounds were confirmed by^(1)H NMR,^(13)C NMR,HPLC and HR-MS(ESI).

关 键 词：手性金鸡纳碱类 3-羟基色酮 (E)-(2-硝基乙烯基)苯 不对称Michale加成反应 控制变量法 

分 类 号：O622.6[理学—有机化学]