硫醇/酚作为路易斯碱催化剂在不对称反应中的应用

Asymmetric catalytic Morita-Baylis-Hillman (MBH) reactions and Rauhut-Currier (RC) reactions have been attracting continuing interest in organic synthesis, since C-C bonds could be directly constructed in an efficient and atom-economical manner with high enantioselectivity. As nucleophilic tertiary amines and phosphines are commonly employed as the catalysts in these reactions, only limited examples were reported with sulfur-containing substances in spite of their high nucleophilicity, suffered from low catalytic activity, stereoselectivity and narrow substrate scope. In the aim of providing potential solutions to these problems, we will design and synthesize multifunctional chiral thiols, which could generate more nucleophilic thiolates in situ. In addition, cooperative thiol-amine and thiol-H bonding donor catalytic systems will be investigated, which might provide better reactivity and stereoselectivity by activating the substrates from multiple sites, and expand the substrate scope. This project aims to develop new thiol catalysts or catalytic systems in asymmetric MBH and RC reactions for the construction of multifunctional chiral products.

不对称催化的Morita-Baylis-Hillman (MBH)反应和Rauhut-Currier (RC)反应能直接、高效构建手性C-C键，具有高原子经济性、高立体选择性等优势，多年来一直是研究的热点之一。该类反应多以亲核性手性叔胺、叔磷作为催化剂，而硫醚、硫醇/酚等化合物很少作为催化剂应用于不对称的MBH、RC反应中，催化活性、立体控制性以及底物普适性等方面都存在很大局限，因此发展高效的基于手性硫醇/酚类化合物催化体系具有重要研究意义。申请人拟设计、合成新型的手性多官能团硫醇/酚类催化剂，易于生成亲核性更强的硫负离子活化缺电子烯烃，并建立硫醇/酚-胺以及硫醇/酚-氢键供体等协同催化体系，通过多位点活化MBH或RC反应底物，改善反应活性和立体选择性，进一步拓展底物范围，并可应用于一些串联反应，构建多官能团手性骨架，为进一步筛选并发现具有生理活性的化合物提供更广泛的物质结构基础。

具有亲核性手性叔胺、叔磷常作为Lewis碱催化剂应用于不对称Morita-Baylis-Hillman (MBH)反应和Rauhut-Currier (RC)反应中，而硫醇/酚类化合物具有更强的亲核性和更小的位阻，却鲜有其作为Lewis碱催化剂的报道。本项目发展了多类新型的手性多官能团硫醇/酚类催化剂；建立了硫酚/叔胺以及硫酚/相转移试剂的协同催化体系；并在这些新催化体系下实现了不对称串联环化反应和去对称化反应。在项目资助下，我们还开发了一类以氧化吲哚为骨架的新型硝酮底物，通过小分子有机催化实现了其参与的多类环化反应和加成反应；另一方面，我们以过渡金属作为催化剂，实现了不对称Barton-Zard反应，也通过钯/相转移催化体系实现了极性翻转的加成反应，合成了轴手性骨架等系列复杂化合物。目前，相关成果共发表SCI论文6篇，包括Angew. Chem., Int. Ed.、ACS Catal. Org. Lett.等高影响力的国际期刊。