The Exploration And Study On Benzyne Involved Oxygen Nucleophilic-Ene Process

The benzoheterocyclic structure is widely present in natural products and drug molecules and plays an important role as a core skeleton.How to construct a benzoheterocyclic skeleton through simple and efficient methods has always been one of the main research concerns by chemists.Since its discovery in 1953,benzyne has been one of the important means to synthesize benzoheterocyclic compounds due to its high reactivity and the ability to construct new chemical bonds on two adjacent carbon atoms.Our research group designed and synthesized a domino 1,2-benzdiyne precursor and accomplished the continuous polyfunctionalization of the benzene ring through a series of process,which provided an effective means for the synthesis of polysubstituted aromatic compounds.In one of the previous research works,our group obtained the product nitrogencontaining benzoheterocycles through the nitrogen nucleophilic-Ene reaction process.By changing the structure of the substrate,the method can also construct a number of nitrogen-containing benzoheterocycles.In addition,using this method,we also prepared a drug,namely Ibutamoren Mesylate,for the treatment of human hormone deficiency,showing its application value.On this basis,we envisioned that we can expand the nucleophilic-Ene reaction process by changing the type of nucleophilic atom with oxygen to obtain oxygen-containing benzoheterocycles product with different structure character,which could further expand the application potential of this protocol.In order to realize this proposal,we designed and synthesized a series of substrates with both an oxygen nucleophilic end and an Ene reaction end.After screening the species with oxygen atom used for the nucleophilic reaction in the substrate and exploring the reaction conditions,the desired product was obtained from 2-(3,3-dimethylallyl)-1,3-cyclohexanedione compound,demonstrating the feasibility of this concept.In the subsequent optimization stage,we also used the stepwise heating method to study the reaction process,which made us a clearer understanding on the reaction process and provided helpful guidance for our subsequent research.