摘要
目的拓展制备3-芳基-2-取代苯并呋喃的合成方法。方法以2-羟基苯基芳基甲酮和醛为起始原料,经交叉型McMurry偶联反应生成邻羟基二苯乙烯衍生物,再经氧化环化得到3-芳基-2-取代苯并呋喃化合物。结果与结论合成了12个3-芳基-2-取代苯并呋喃化合物,其中4a、4b、4f、4j为已知化合物,其余8个为新化合物,分离总收率在48%~80%1,2个化合物的结构经IR1、H-NMR1、3C-NMR、HR-MS(EI)谱确证。该两步法合成路线具有原料易得,反应条件温和,易于操作等优点,且收率较高,适于较大量制备。
The 2,3-disubstituted benzofuran nucleus constitute the core skeleton of an increasing number of natural and artificial products that possess a wide range of biological activity.In our previous work,A two-step synthetic strategy for 2-arylbenzofurans based on the selective cross-McMurry coupling of substituted salicylaldehyde with an aromatic aldehyde has been developed as well.As part of our continuous effort to find better approach to 3-aryl-2-substituted benzofuran,a selective cross McMurry coupling between a 2-hydroxyphenyl aryl methanone and an aldehyde,and a sequential oxidation of the resulting ortho-vinylphenols were employed.After a survey of the type and amount of low valent titanium,optimal conditions for cross McMurry couplings employed 2.5 equiv of TiCl4-Zn with a 1∶ 1.2 mol ratio of 2-hydroxyphenyl aryl methanone(1a or 1b) to an aldehyde(2a-2j).For the oxidative cyclization of the ortho-vinylphenols(3a-3l),The results revealed that the cyclization of the ortho-vinylphenols produced from the couplings between 2-hydroxyphenyl aryl methanone(1) and an aliphatic aldehyde(2h-2j) was achieved using DDQ,while the others could be achieved employing I2/K2CO3 in most cases,and the total isolated yield was between 48%-80%.Twelve compounds of 3-aryl-2-substituted benzofurans were confirmed by IR,1H-NMR,13C-NMR and HR-MS(EI).Among them,eight were novel compounds.The advantages of this synthetic approach are:1) the reagents are readily available;2) the conditions are mild and the operations are simple;3) the preparations are suitable for scale-up.
出处
《中国药物化学杂志》
CAS
CSCD
2011年第3期208-212,共5页
Chinese Journal of Medicinal Chemistry
基金
国家自然科学基金项目(20672014)
国家高技术研究发展计划项目(2004AA234050)部分资助