Visible Light-Induced C-N and C-C Coupling Reactions

Author:Liu Fang Zuo

Supervisor:yang yi wen zhang zhi guo


Degree Year:2018





With the growing urbanization process,energy shortage has become increasingly prominent.How to use solar energy efficiently has become the focus of research.Among them,visible light as a green energy is renewable and environmentally friendly.As thus visible light mediated synthesis of functional chemicals has grown into an important branch of synthetic chemistry.Visible light can promote electron transfer between the catalyst and the substrate under mild conditions,thus reduce the activation energy of the reaction in a green and efficient way.In recent years,with the development of visible light catalysis,the visible light mediated catalytic strategy provides new ideas for the functionalization of nitrogen-containing substrates and the synthesis of heterocyclic derivatives.This thesis first summarizes the latest research progress in this field,and then we report our work on the visible light-catalyzed functionalization of tertiary amines and synthesis of nitrogen-containing heterocyclic derivatives.Conventional C-N cleavage reactions are typically catalyzed by transition metal catalysts,which are generally encountered with a harsh reaction condition and a limited substrate scope.Herein,we first report the visible light mediated C-C coupling reaction between tertiary amines and active alkynes.The strategy uses the organic dye Eosin Y as a photosensitizer,which completes N-dealkylation addition of tertiary amine with dialkyl acetylenedicarboxylate under mild conditions.This reaction has a wide range of substrate scopes and provides a new approach for synthesis of maleic amide.With the optimization of oxidant and the presence of alkali additive,the reaction efficiency and product yield are successfully improved,and the highest yield can reach up to 95%.At the same time,we systematically studied the reaction mechanism by means of analytical methods such as NMR and GC-MS.Based on our proposed photocatalytic triamine dealkylation strategy,the synthesis of a-ketoamide derivatives was further extended.a-Ketoamide is an important core skeleton in drug molecules,which is also an important synthon for futher functionalization and transformation.The preparation of a-ketoamide under mild conditions was achieved by N-dealkylation coupling using cheap and readily available carboxylic acid as a raw material and a tertiary amine as a nitrogen source.This reaction is simple in operation and does not require nitrogen protection,which provides a new access to a-ketoamide derivatives under mild conditions.Oxindole is an important nitrogen heterocyclic compound,which is widely present in natural products as a core skeleton.Based on the visible light mediated radical activation of halide,the synthesis of oxindole derivatives at room temperature was developed.Bromoacetonitrile and phenylacetyl bromide were used as alkylating reagents.The reaction can be carried out at room temperature without using an additional free radical initiator.The operation is simple,and a series of cyanomethyl and phenylacetyl substituted oxindole derivatives were synthesized in excellent yield(75-97%).At the same time,the free radical reaction mechanism was investigated by the free radical scavengers.In view of the halide recognition and chiral manipulation with thiourea derivatives,we attempted to prepare chiral oxindole derivatives via synergistic catalysis of thioureas and photocatalysis.Through systematic research,we have successfully achieved the cycloaddition reaction of inert bromine with active olefins by thiourea catalysis and photocatalysis synergistically,and the synthesis of chiral oxindole skeleton has been explored.It is the first time to use synergstic method to synthesis of oxindole derivatives,and the reaction yield was improved from 28%to 96%by introducing thiourea molecules.The method enriches the structural diversity of the oxindole bioactive molecules,which has a wide range of applications.This protocol also provides a new way for preparing oxindole compounds under mild conditions.