Photocatalyzed Cross-dehydrogenative Coupling Reaction Of N-carbamyl Tetrahydroisoquinolines With Enones

N-Heterocycles are important skeletons of many bioactive compounds and key intermediates in chemical synthesis.Functionalization of the C-H bond adjacent to a nitrogen atom can increase the structural diversity and complexity.Therefore,the research on this respect has attracted considerable interest.Among such methods,cross-dehydrogenation coupling?CDC?reactionhas been favored,as which presents an atom-economicprotocol.Tetrahydroisoquinoline?THIQ?is commonly used as a template substrate to study the C-H bond functionalization of?-nitrogen.In charpter 1,the CDC reseaches on the C1 C-H bond of THIQ are reviewed.Currently,a series of CDC reactions of tetrahydroisoquinoline have been reported,including metal catalysis,metral-free oxidation,electrocatalysis,photoredox catalysis.Visible-light-mediated photocatalytic CDC reaction of N-protection THIQ has obtained extensive attention as a capable and environmentally benign method.Among the existing reports,nucleophiles as unactivated ketones and unsaturated ketone was less reported.Moreover,in these reports,N protective group of tetrahydroisoquinolinesis usually aryl,but aryl is difficult to remove for subsequent reaction.Compared to N-aryl protection,N-acyl and N-carbamyl protection decreased the reactivity of THIQ,and only a few examples have been reported.Considering of the importance of the structure and subsequent application research of tetrahydroisoquinolines substituted by enoneat the C1 position,charpter 2 of this thesis focuses on the photocatalyzed cross-dehydrogenation coupling reaction of N-carbamyl tetrahydroisoquinoline with enones.Based on thorough and careful studies,we have developed a photocatalytic crossdehy-drogenation coupling reaction of N-carbamyl tetrahydroisoquinoline with enone.The reaction was carried out with Ru?bpy?3Cl2·6H2O?1mol%?as the catalyst,?NH₄?₂S₂O₈?2 eq.?as the oxidant under the arradiation of 10W blue LEDs for 6h,to afford C1 enone-substituted tetrahydroisoquinoline which can be further converted into a benzo-[?]-quinolinazin-2-one compounds.This method is characterized by mild reaction conditions,good functional group compatibility,easy-operation and environmental friendly process,and would be used in the development of new medicines.