Electrochemical Cross-dehydrogenative Coupling Of N-aryl-tetrahydroisoquinolines With Phosphites And Indole

The construction of C-P and C-C bonds is an important research contents in the field of organic synthesis.Catalytic formation of C-P and C-C bonds are one of the most valuable processes in organic synthesis,because they are critical steps in the synthesis of complex molecules.Cross-dehydrogenative coupling（CDC）is a highly efficient method for constructing C-C and C-X bonds.It has advantages of high atomic utilization and simplicity,and conforms to the concept of green chemistry.Direct formation of C–P and C–C bonds by oxidative CDC reaction is an attractive research area in organic synthesis,since pre-functionalized precursors is not required in CDC methods,which are atom economical and environmentally benign.Electrochemical synthesis is sustainable and eco-friendly in comparison with the conventional redox processes,because electrons are employed as reagents without the existance of transition-metal catalysts or toxic oxidants.we introduced the electrochemical cross-dehydrogenative coupling of N-aryl-tetrahydroisoquinolines with phosphites and indole to construct C（sp³）-P,C（sp³）-C（sp²）bonds without the use of any oxidants,and the synthesis method has wide functional group tolerance.This paper is mainly divided into the following three chapters.In the first chapter,we introduced the research history,the research progress,advantages and future prospects of organic electrochemical synthesis,and then we summarized the literature on the construction of C（sp³）-P,C（sp³）-C（sp²）bonds by CDC reaction.In the second chapter,we mainly introduced the electrochemical cross-dehydrogenative coupling of N-aryl-tetrahydroisoquinolines with phosphites and indole.For synthesizing diethyl（2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl）phosphonate as the model reaction,we investigated the effects of reaction factors such as solvents,electrolytes,and electrode materials on the reaction results.Finally,we identified the optimal reaction conditions,which involved 5 mA constant-current electrolysis using a graphite rod anode and a Pt plate cathode,in an undivided cell containing an electrolyte solution of n-Bu₄NBr in CH₂Cl₂ at room temperature,the diethyl（2-phenyl-1,2,3,4-tetrahydroisoquinolin-1-yl）phosphonate was obtained in a yield of 83%.Next,we synthesized the precursor N-aryl-tetrahydroisoquinoline compounds,and investigated the substrate suitability of the CDC reaction under the above optimal conditions.It shows that mild electron-withdrawing substituents generally offer a higher yield than strong electron-donating group or strong electron-withdrawing one.Then we changed the phosphite to free indole,in this work,free indole could react with a variety of tetrahydroisoquinolines to give the desired products in moderate to good yields with an exclusive regioselectivity.It shows that the synthesis method has wide functional group tolerance.By reviewing the literature and analyzing the experimental results,we predicted the reaction mechanism,N-aryl-tetrahydroisoquinoline generate the iminium-ion intermediate on the anode,then iminium-ion intermediate is captured by the reactive nucleophile to afford the CDC product.In the third chapter,we introduced the synthesis methods of precursor materials,the methods of the electrochemical cross-dehydrogenative coupling of N-aryl-tetrahydroisoquinolines with phosphites and indole,the nuclear magnetic data and the nuclear magnetic spectrum of precursor materials and products.In summary,we have successfully developed an electrochemical CDC reaction of tetrahydroisoquinolines with phosphites and indole using an undivided cell.This reaction could be carried out at room temperature without the use of any catalysts,oxidants or additives.This process offers an alternative to conventional methods that require metal catalysts or chemical oxidants and represents an environmentally benign tool for oxidative C（sp³）-P and C（sp³）-C（sp²）bonds formation.