镍(II)-氟硼二吡咯光敏剂可见光协同催化的偶联反应研究

The merger of nickel and photocatalysis, termed as a powerful tool, has supplied a novel strategy for the transformation of C-C and C-X bonds. In the past decade, photoredox/Ni dual catalysis have focused predominantly on ruthenium and iridium polypyridyl complexes. Meanwhile, there have less report on nickel and organic photoredox catalysis. Base our previous work, this proposal will carry on the cross-coupling reactions via organic photoredox/nickel dual catalysis using BODIPY as photocatalyst. Our works focus on two issues: one is how to efficiently achieve the nickel catalytic cycle under photoredox/nickel dual catalysis using BODIPY; another is how to oxidize Ni(II) species to Ni(III) species directly by the excited photocatalyst following reductive elimination to form the product at the Ni(III) center. This project will establish nickel/BODIPY dual catalysis system and develop new methodology for transformation of C-C and C-X bonds. Together with the use of an inexpensive metal catalyst, an organic photosensitizer, this feature makes the protocol practically valuable for the synthesis of pharmaceutical.

可见光催化与镍催化结合，为碳-碳键或碳-杂键的构建提供了一种新的研究思路。镍与铱、钌等金属光敏剂结合的双催化体系研究较多，以有机染料为光敏剂的协同催化体系较少。基于前期的研究，本项目拟开展可见光催化下，以有机染料氟硼二吡咯烷为光敏剂，镍(II)-氟硼二吡咯可见光协同催化的偶联反应研究，主要解决两个问题：（1）以氟硼二吡咯烷为光催化剂，前催化剂镍(II)在可见光促进下，如何高效实现镍催化剂的循环；（2）在底物的参与下，镍催化体系与光催化体系如何实现有效的协同作用，使不易发生还原消除的Ni(II)活性物种氧化为Ni(III)物种，促进还原消除，完成催化循环。本项目为克服传统偶联反应存在的问题，开展特色光催化反应研究和发展新的合成发法学建立了研究基础。该项目的研究具有重要的基础研究价值，也为发展具有自主知识产权的药物合成工艺提供了基础。

光催化与镍催化结合，为碳-碳键或碳-杂键的构建提供了一种新的研究思路。本项目发展了光促进镍催化催化醇与芳基亲电试剂的醚化反应；发展了光促进镍催化卤代芳烃与硝基苯C-N偶联反应和光促进镍催化手性胺与芳基亲电试剂芳基C-N键偶联反应。我们首次提出可见光激发廉价的二价镍产生活性Ni(I)物种，然后与卤代芳烃发生氧化加成生产Ni(III)中间体。接着，中间体Ni(III)物种与弱亲核试剂发生配体交换。最后，中间体Ni(III)物种还原消除得到目标产物，完成催化循环。通过UV、EPR及HRMS等对反应中间体进行检测和表征，并提出可能的反应机理。发展的反应体系，为复杂活性分子的后期修饰提供了可行新的策略。