【作者】 张雪梅；

【导师】 尚会建； 孙慧； 赵宝山；

【作者基本信息】 河北科技大学 ， 制药工程（专业学位）， 2021， 硕士

【摘要】 羰基α位的官能团化反应是构建C-O键的重要方法。羰基α位的官能团化反应,在重要天然产物和药物分子关键中间体的合成中有重要的研究意义。传统的合成策略是在强碱作用下,羰基α位生成烯醇负离子,与各个类型的亲电试剂发生重排或偶联环加成反应,这类反应存在原子经济性低,环境不友好,反应条件苛刻等缺点。近年来,随着精细化学和绿色化学理念的不断拓展,对化学合成在原子经济性方面提出了更高的要求。本论文将通过多米诺反应一锅法实现羰基α位酰氧基化反应,其原子经济性和可操作性强,操作简便,节省试剂,是一种高效的绿色合成方法。羰基α位酰氧基化反应通过两步连续的反应实现:以酮为底物,在铜盐的作用下与N,N-二烷基酰胺类化合物反应得到酰氧基酮类化合物。实验通过对铜盐、反应时间、反应温度、溶剂等的筛选得到最优反应条件。该反应的过程是溴化铜与各种酮类化合物发生取代反应,得到α-溴代酮,同时在反应中生成溴化亚铜。随后N,N-二甲基甲酰胺作为亲核试剂与α-溴代酮反应得到亚胺类化合物,亚胺类化合物再经过水解得到甲酰氧基类化合物,分离产率高达95%。该反应通过多米诺反应的方法直接得到羰基α位酰氧基化产物,收率良好,底物适用范围广泛,中间产物无需分离,操作简便,具有高度的原子和步骤经济性。更多还原

【Abstract】 α-Functionalization of carbonyl compounds is an efficient method to construct C-O bond.α-Functionalization of carbonyl compounds has great research value in the synthesis of natural products and intermediates of drugs.The traditional synthesis strategy is that the carbonyl compounds generate enol anion which is rearranged or coupled with various types of electrophilic reagents under the condition of strong base.This kind of reaction has many disadvantages such as low atomic economy,unfriendly environment,and harsh reaction conditions.In recent years,with the development of green chemistry,the atomic economy in chemical synthesis has been put forward for higher requirements.In this paper,α-acyloxylation reaction is achieved by domino strategy which has the advantage of atomic economy,easy to operate,reagent saving,and time saving.The α-acyloxylation of carbonyl compounds is achieved by domino strategy.The products were obtained with N,N-dialkylamides in the presence of copper salts.The optimal reaction conditions were obtained through the screening of copper salt,reaction time,reaction temperature,and solvent.The reaction process is the substitution of copper bromide with all kinds of ketone to obtain α-bromoacetone and Cu Br.DMF reacts withα-bromoacetone to obtain imines.Imines are then hydrolyzed by H2 O to form final product.The separation yield is as high as 95 %.The products are obtained directly by domino strategy with good yields,wide reaction scope,simple operation,and high atomic economy.更多还原