炔丙醇与异氰的联烯化、烯化反应研究

Allenes and alkenes are two classes of important organic compounds with rich reactivity and wide synthetic applications. Therefore, the development of new organic reactions leading to these two types of compounds is of great significance. More recently, we have made an original discovery that allenes and alkenes can be constructed by the reactions of propargylic alcohols with isocyanides. On the basis of this interesting finding, the project group intends to deeply and systematically study these two new reactions, and develops an atom-economic allenylation of readily-available propargylic alcohols with isocyanides by using the cheaper metal salt catalyst, which would enrich the chemistry of allenes. In the meanwhile, we are going to design tandem intermolecular allenylation and intramolecular cyclization reactions, aiming to make some important carbo- and heterocycles. In addition, the project team will develop a highly efficient olefination reaction of propargylic alcohols with toluenesulfonylmethyl isocyanides, yielding synthetically useful vinyl sulfones, and then apply this method to the synthesis of anti-breast cancer drug tamoxifen and toremifene, respectively. Eventually, we hope to develop and establish a new class of organic synthetic methodology based on the allenylations and olefinations of propargylic alcohols with isocyanides.

联烯和烯是两大类重要的有机化合物，拥有丰富的反应性以及广泛的合成应用。因此，发展新的有机反应合成这两类化合物具有重要研究价值。最近，申请人课题组原创性发现了一类新颖的炔丙醇与异氰的联烯化、烯化反应。在此基础上，本项目组拟深入、系统研究这两种新反应，具体研究内容包括：从简单易得的炔丙醇和异氰出发，利用廉价金属盐催化剂，发展一种原子经济性炔丙醇与异氰的双组分联烯化反应，丰富联烯化学的内容；发展分子间炔丙醇-异氰联烯化/分子内环化串联反应，为一些重要碳环、杂环化合物的合成提供新方法；建立一种高效炔丙醇与璜酰基异氰的烯化反应，制备合成上有用的烯基砜化合物，并应用该方法合成抗乳腺癌药物他莫昔芬、托瑞米芬。本项目研究目标明确，前期工作基础坚实，研究内容相互关联、系统深入，形成了一类新颖的以炔丙醇-异氰联烯化、烯化反应为核心的有机合成方法学。

在项目执行期间，项目组取得了系列创新性研究成果，包括：（1）提出了银催化σ-活化炔烃策略，发展了系列基于炔烃活化的新反应；（2）发展了银催化σ-活化异氰的方法，实现了异氰的多种高效转化；（3）发展了一系列银催化donor-型重氮化合物的活化及转化反应。共发表论文39篇，其中包括Angew Chem. Int. Ed. 3篇，Org. Lett. 12篇，Chem. Commun. 4篇等。研究成果得到了国内外同行的广泛关注，被期刊遴选为VIP文章、封面文章、Hot Paper以及被Synfacts、Synform等报道二十余次。项目负责人相继获得国家自然科学基金委优秀青年基金（2015），入选教育部“长江学者奖励计划”青年学者（2016）。