光敏剂DPZ与手性NHI协同催化不对称有氧氧化去对称化反应

Asymmetric cooperative catalysis has long been acknowledged as a powerful tool for constructing valuable and complex chiral compounds. Along with the rapid growth of the highly sustainable photochemistry, in recent years, cooperative photoredox and asymmetric catalysis (CPAC) has attracted increasing attention of chemists. A number of dual catalytic systems through combining photoredox catalysts with chiral catalysts have been impressively established. However, rare variants in transition metal-free manner have been described to date, which represents a highly desirable task for their significant potentials in medicinal chemistry. Recently, we developed a dicyanopyrazine-derived chromophore (DPZ) as a new type of metal-free photoredox catalyst that facilitated a series of achiral transformations with low catalyst loadings (between 1.0 mol% and 0.01 mol%). The prominent performance of DPZ promoted us to assess its potential in the ever-growing CPAC. Herein, we would be engaged in investigating four kinds of challenging asymmetric aerobic oxidative desymmerization reactions by developing cooperative DPZ-based visible light photoredox with chiral N-hydroxyimide (NHI) derivatives catalysis. Three types of novel chiral NHIs, including Einhorn-, binaphthalene-, and amino acid-based variants, will be synthesized. The obtained chiral NHIs should be attempted as the chiral organocatalyst in the desired transformations. We believe that this work will provide a novel transition metal-free CPAC system in photochemistry, which can be a promising tool in other undeveloped reactions. More importantly, this contribution will present feasible inspirations in the development of novel cooperative photoredox and asymmetric catalysis.

随着可见光催化的蓬勃发展，可见光不对称协同催化近年来受到化学家的广泛关注，并已成为不对称催化的重要手段之一。然而，关于无重金属残留的可见光不对称协同有机催化的相关研究迄今仍然非常有限。申请人依据前期在不对称有机催化及可见光有机催化的研究基础，提出开展光敏剂DPZ与手性N-羟基酰亚胺（NHI）协同催化不对称有氧氧化去对称化反应研究。申请人将基于合成Einhorn骨架、联二萘骨架及氨基酸骨架等三类手性NHI，通过建立DPZ与手性NHI的协同催化体系，在低能耗可见光照射下完成四类富有挑战性的不对称有氧氧化去对称化反应，力求获得高产率及高立体选择性。期待通过这一课题的开展，能够为可见光不对称协同有机催化提供一个具有广泛应用前景的催化体系，从而将其作为有力工具挑战并完成更多新类型反应，同时为其它新颖协同催化体系的设计提供有用思路。

在本基金资助下，使用自主研发的高效可见光有机光敏剂DPZ，建立DPZ与手性质子酸协同可见光不对称催化平台，发展包括还原质子化、还原脱卤质子化、自由基共轭加成—质子化等系列新型不对称质子化反应，并将之有效拓展至利用氘水作为氘源的还原及还原脱卤不对称氘化反应；不对称Minisci反应；不对称还原偶联反应；不对称自由基偶联反应等。所有反应通过自由基途径所产生的负离子中间体或自由基中间体参与手性中心成键，并利用手性质子酸提供手性诱导，实现了高化学选择性与立体选择性，凸显这一催化平台的高效性。同时，完成手性NHI催化剂库的建立，利用DPZ与手性NHI协同催化致力于本基金申请课题相关研究，已取得突破性进展。此外，对于具有重要研究意义的不对称直接vinylogous反应，发展了新型氮杂芳烃底物类型用于氮杂芳烃远程手性中心构建，发展了多氢键与反离子键协同催化平台，实现了惰性底物参与不对称vinylogous反应。资助期间，在J. Am. Chem. Soc.、Angew. Chem. Int. Ed.、Nat. Commun.等学术期刊发表学术论文31篇，其中2篇为ESI高被引，1篇入选JACS Spotlights，5篇被Synfacts收录（其中一篇为Synfacts of the Month）；课题负责人相继入选百千万人才工程国家级人选、国家有突出贡献中青年专家、享受国务院特殊津贴专家、河南省优秀专家以及河南省杰出专业技术人才；获2019年国家杰出青年科学基金资助；获河南省科技进步二等奖；培养的朱博同学获国家博士后创新人才支持计划；4位同学获河南省优秀硕士学位论文。