N-heterocyclic carbene-catalyzed single-electron-transfer radical processes for reductive coupling reactions

• Main Author: Wang, Yuhuang
• Other Authors: Chi Robin Yonggui
• Format: Theses and Dissertations
• Language: English
• Published: 2018
• Subjects: DRNTU::Science::Chemistry
• Online Access: http://hdl.handle.net/10356/73859
• Institution: Nanyang Technological University

This thesis focuses on exploring single-electron-transfer (SET) reductive coupling reactions catalyzed by N-heterocyclic carbene (NHC) organocatalysts. It contained five chapters: Chapter 1 gives a brief introduction to NHC-catalyzed electron-pair transfer reactions involving different key intermediates, and recent discoveries on NHC-catalyzed SET process and relating reactions. Chapter 2 describes a carbene-catalyzed reductive coupling reaction for β-nitroalkenes. The reaction pathway includes SET process mimicking the thiamine pyrophosphate (TPP)-catalyzed oxidative decarboxylation of pyruvate in living systems. The SET process starts from Breslow intermediate of nitroalkene to generate corresponding nitroalkene radical anion for further transforming to homocoupling product. For the first time, the presence of radical anion intermediate in NHC-organocatalytic system is revealed. Chapter 3 introduces a carbene-catalyzed reductive cross-coupling of nitrobenzyl bromides with nitroalkenes via SET process and formal 1,4-addition. Control experiments prove that the reaction initiates from the SET process between nitrobenzyl bromide and Breslow intermediate. The nitrobenzyl bromide first obtains one electron, and the elimination of bromide takes place during the following generation of corresponding nitrobenzyl radical intermediate for further transformation. The bromo group serves as a leaving group in this reaction. The reaction pathway shows a new activation mode in NHCorganocatalysis. Chapter 4 describes a carbene-catalyzed reductive cross-coupling of nitrobenzyl bromides with ketones or imines via SET process and formal 1,2-addition. This reaction utilizes the nitrobenzyl radical intermediate, which generates via single-electron reduction of nitrobenzyl bromide and elimination of bromide, to react with α,β-unsaturated ketoesters,isatins and sulfonyl imines. The reaction provides tertiary alcohols and tertiary amines as the desired products, and the products are further transformed to other interesting molecules including nature product. This work expands the utilization of our NHC-catalyzed SET process. Chapter 5 develops an efficient carbene-catalyzed cascade process for the synthesis of indane ring systems. The reaction includes the initial SET process for the formal 1,4-addition of nitrobenzyl radical to nitroalkene, and follows another SET process to give corresponding anion intermediate, then the intramolecular Michael addition and protonation takes place to form the indane derivative. The diastereoselectivities of the reaction are excellent that for each of the products, only one diastereomer can be observed. This work demonstrates the synthetic utilization of our NHC-catalyzed new activation mode which involving SET process as key process.