腈类碳钯化水解参与烯烃氧(氮)酰基化的成环反应研究

As a kind of extensive sources, cheap and easiyl available, nitriles and alkenes are important organic chemical raw materials, which can undergo diverse reaction of functional group. It shows that catalysed by palladium, nitriles can generate carbopalladium and then protonation hydrolysis to obtain direct acylated products, which were used equivalently as the acylated reagents; Alkenes can generate 1,2-difunctionalization reactions to obtain products of structural diversity. All these two types of reactions are more reported. We previously studied the selective acylations of free (N-H) indoles and thiophenes using nitriles as effective acylated reagent. On the base of these results, we further investigate the heteroacylation reactions of alkenes combined carbopalladium of nitriles with difunctionalization of alkenes process, which have little reported. In this project oxa(aza)acylation cyclization of alkenes were studied by suitalble substrate design, the main content include: construction of 2-acyl methylated dihydrobenzofurans or dihydrobenzoindoles derivatives using ortho-hydroxyl(amino)allylbenzenes with nitriles; construction of 3-acylated dihydrobenzofurans or dihydrobenzoindoles derivatives using ortho-alkenyl phenols(anilines) with nitriles. Then detailed mechanisms were explored about this type of reactions. Through the study of this project, difunctionalization of alkenes were futher enriched, and some theoretical and practical guidances were got for the design and synthesis of some important bioactive molecules.

腈和烯烃都是重要的有机化学原料，来源广泛，便宜易得，可进行官能团的多种化学反应。研究表明在钯催化下，腈可发生碳钯化并质子化水解得到酰基化产物，相当于在反应中作为酰基化试剂；而烯烃可发生1,2-双官能化的反应得到结构多样性的产物，目前这两类反应报道都较多。申请者前期研究了腈的碳钯化水解过程参与吲哚和噻吩选择性酰基化反应，取得很好效果。在此基础上我们将腈的碳钯化过程提供酰基的反应与烯烃的双官能化反应相结合来探究烯烃的杂酰基化反应，而烯烃的杂酰基化反应报道较少。该项目主要研究烯烃的氧(氮)酰基化的成环反应，内容有：邻羟基(氨基)烯丙基苯与腈反应构建苯并二氢呋喃(吲哚)的2位酰甲基化产物；邻烯基苯酚(胺)与腈反应构建苯并二氢呋喃(吲哚)的3位酰基化产物，然后并对反应机理进行详细的研究。该项目的研究进一步丰富了烯烃的双官能化反应，并为设计和合成一些重要的生物活性分子提供理论和实践指导。

本项目希望通过钯催化下发生腈类碳钯化过程提供酰基实现烯烃双官能化反应合成杂环化合物，为了实现这类反应，首先设计了不同的底物包括分子间反应和分子内反应，并经过大量的实验条件摸索，如不同的钯催化剂、各种配体、添加剂等，遗憾的是没有实现预期的实验目标。可能的两个关键原因是烯烃beta-氢消除不可避免，配体的引入抑制了腈类参与反应；然而实验中我们有了两个新的发现并进行了系统的研究：（1）实现了无金属条件下DDQ氧化烯芳基丙基合成肉桂醛类化合物的方法，同时将其应用于植物次生代谢物的简单高效合成；（2）实现了直接的空气氧化无金属条件下质子酸活化DMSO提供C1单元参与喹啉类化合物的精准合成研究，通过此方法简单快速实现了4位取代和3位酰基取代的喹啉类化合物，为溶剂DMSO参与反应和新型杂环化合物的绿色合成提供了新思路。