苄基醚参与的Csp3-H官能团化研究

Recently the development of efficient methods towards carbon-carbon bond through the direct functionalization of sp3 C-H bond has become a growing area of investigation. Therefore the development of new synthetic strategy of sp3 C-H bond functionalization, especially unactived C-H bond, has become a significant and challenging area. Some endeavours were achieved to develop this powerful transformation using noble metals to afford formation od C-C, C-X bonds, especially tetrahydroquinoline derivatives. However, there are relatively few reports the sp3 O-C-H functionalization: successful cases were mostly concentrated in name organic reactions, and the range of substrates is also very limited. We wish to develop new synthetic strategy by using common metal, or organic oxidants, or dehydrogenated reagents, which will allow the efficient to construct oxygenous heterocylces. Finally we wish to apply the developed direct method in the asymmetric catalysis of benzylic ethers. It would also provide assistance and relief in the diversity-oriented synthesis, biological activity studies, and structure-activity relationship studies. Furthermore, it is hoped that the more efficient and effective application of the developed chemistry will improve the drug discovery process.

近年来通过直接的C sp3-H官能团化构建新的化学键已成为有机合成方法学研究的前沿和热点之一，大部分工作通过贵金属实现含氮化合物的C-H官能团化，如四氢异喹啉。但是关于氧原子邻位的官能团化研究较少，已有报道多集中在一些活泼亚甲基参与的反应，同时对于直接的不对称反应的研究也非常少。本研究期望利用非贵金属（如Fe、Cu）、有机氧化试剂（高价碘等）和脱氢试剂（如DDQ等）单独或共催化实现苄基醚类化合物的官能团化，高效、快速地实现一些含杂环骨架的构建，为该类化合物的不对称的引入提供新的最直接的方法及途径。通过本项目的实施，可以为氧原子α位的官能团化及活性化合物的合成提供新的思路及方法。

发展了一些基于苄基特别是苄基醚相关的方法学研究，实现了申请书中CN、C-O键、C=C、C=O等在非金属催化下的引入；发展了苄基醚参与的1,2苄基迁移重排反应、分子内的频哪醇重排反应等，同时以该重排反应为关键步骤，实现了具有重要生物活性化合物平板霉素的形式全合成；实现了苄基醚一步高效转化为苯甲腈衍生物；在强碱的促进下完成了3-芳基-2-烷基苯并呋喃的高效快速合成，并以此为基础发展了DMSO作为甲基化试剂通过串联的aldol缩合、Michael加成及异构化实现了3-芳基-2-甲基吲哚的合成，为活性天然产物和其它药物的合成奠定了一定的基础。 . 在项目的资助下，共发表SCI论文7篇，其中一区论文3篇，二区论文1篇。授权国家发明专利1项。. 培养毕业5名硕士，在读硕士3名。