基于芳炔和Baylis-Hillman 反应产物的选择性苯并杂环合成

Arynes are highly reactive intermediates that used widely in heterocycle synthesis and natural product synthesis.In this project, based on our previous work on aryne chemistry and Baylis-Hillman reaction,the selective cycloaddition of arynes and Baylis-Hillman adducts will be investigated. Using bond-insertion strategy, aza-Baylis-Hillman adducts, Baylis-Hillman adducts as well as their derivatives can react with arynes to construct benzoheterocycles. The chemo- and stereoselectivity can be manipulated by modifying the steric and electronic properties of Baylis-Hillman adducts with assistance of Lewis acid.A series of problems that exist in the synthesis of benzoheterocycles,such as multi-step reaction,harsh reaction conditions,limited scope of substrates and functional group will be solved. Meanwhile, a mild, conscious and transition-metal-free protocol for the synthesis of tetrahydroquinoline,tetrahydrobenzo[b]pyran and other nitrogen or oxygen-containing heterocycles will be developed. Through the implementation of this project, new method for the synthesis of benzoheterocycles will be developed, which will push the progress of aryne chemistry as well as heterocyclic chemistry.

芳炔是一类重要的活性有机中间体，在杂环合成和天然产物合成中都有着广泛的应用。本项目在前期芳炔环加成反应和Baylis-Hillman反应两部分工作的基础上，进一步对芳炔与BH反应产物的选择性环加成反应开展研究。采用插入-环化串联反应策略，利用氮杂BH产物、BH产物及其衍生物与芳炔的环加成反应构筑苯并杂环类化合物。通过对BH产物结构、电性以及空间位阻等因素的调节，并结合Lewis酸等添加剂，实现对这类芳炔环加成反应化学选择性和立体选择性的有效调控。解决这类杂环合成中存在的反应步骤复杂、反应条件苛刻以及底物和官能团兼容性较差等问题，发展温和条件下，非金属催化"一步法"合成多官能团化四氢喹啉、苯并四氢吡喃等氮、氧杂环及其衍生物的简洁方法。通过该项目的实施，发展新的杂环合成方法学，同时可以促进芳炔化学和杂环合成化学的发展。

苯炔作为一类高活性的有机中间体，在有机合成中有着重要应用。本项目利用苯炔为关键中间体，研究了苯炔与aza-Morita-Baylis-Hillman 加成产物的插入-环化-ene串联反应；同时对苯炔与邻亚甲基苯醌的Diels-Alder反应等进行了研究，发展了合成喹诺酮、氧杂蒽等重要化合物的合成新方法。主要研究内容包括以下几个方面：.(1) 苯炔与aza-Morita-Baylis-Hillman 加成产物的插入-环化-ene串连反应.(2) 苯炔与邻亚甲基苯醌的Diels-Alder反应.(3) 苯炔与邻酚羟基邻亚甲基苯醌的插入-环化反应.(4) 苯炔与芴衍生的烯烃或芳基亚胺的环加成反应.(6) 苯炔诱发的喹啉、异喹啉的去芳构化.(7) 苯炔与环硫醚、亲核试剂的多组分反应.(8) 苯炔与环状氨基酮的插入-环化反应