Study On Synthesis Of Quinoline Derivatives By [5+1] Cyclization Of 2-Vinyl/Arylanilines

Quinoline compounds as a class of extremely important nitrogen-containing heterocyclic compounds are widely found in natural products and fine chemicals,which are used in many fields such as synthetic chemistry,material chemistry,medicinal chemistry and catalysis.There are many traditional synthesis methods of quinoline derivatives,mainly focusing on aromatic amines as starting materials.Notwithstanding robust enough,these conversions still encounter several restraints such as limited products,harsh condition,poor selectivity and low yield,therefore,the development of effective synthesis methods for quinoline derivatives have always been a subject of concern.In recent years,the[5+1]annulation of 2-substituted anilines with different Cl coupling reagents have gradually become one of the most effective strategies for contructing quinoline derivatives although the corrent types of highly active C1 coupling segments are still limited.Based on this background,we herein explore more abundant Cl coupling segments for synthesis of quinoline derivatives from 2-substituted anilines via[5+1]cyclization.The main contents are as follows:(1)An example of Ru(?)-catalyzed[5+1]annulation of 2-vinylanilines with sulfoxonium ylides was developed.The optimized reaction conditions were determined by screening catalysts,solvents and additives.With the optimized reactions in hand,the scope of 2-vinylanilines and sulfoxonium ylides was investigated,and 44 examples of 2-acylquinolines were successfully synthesized with good yields(up to 91%yields)and excellent functional group tolerance,including different electric effects and steric hindrance.Several derivatizations on products were performed such as cycloaddition,dearomatization and C-H functionalization.According to the investigation of reaction process,a tentative mechanism was proposed that this reaction underwent C-H activation,migration inserts of carbene,reductive elimination and oxidative aromatization.This transformation employed free amino as a directing group to activate alkenyl C-H with high selectivity,and established a method for the synthesis of 2-acylquinolines by[5+1]cyclization using sulfoxonium ylides as C1 synthesizer.(2)An acid-actalyzed[5+1]cyclization reaction of 2-vinylanilines with?-dicarbonyl compounds was accomplished.The optimized reaction conditions were determined by screening solvents,catalysis and temperatures.The scope of 2-vinylanilines and ?-dicarbonyl compounds was examined under the optimal conditions.A series of 2-vinylanilines could achieve this transformation with good functional group toleration.?-Dicarbonyl compounds,including ?-ketoesters and?-diketone were suitable for this reaction,and 39 examples of 2-substituted quinolines were successfully synthesized in good yields(up to 89%yields).The C-H functionalization of multiple directional sites of quinolines were synthesized by C-H activation with diverse coupling reagents.Based on the investigation of mechanism,it was suggested that the reaction underwent nucleophilic addition,aza-Prins cyclization and retro-aldol.This reaction developed a cyclization between 2-vinylanilines with ?-dicarbonyl compounds as masked C1 synthons via C-C bond cleavage,thus high-selectively delivering 2-alkyl,fluoroalkyl and aryl substituted quinolines.Remarkably,desired products could also be obtained through three-component[3+2+1]reaction involving anilines,aromatic acetylene and ?-ketoesters.(3)An acid-promoted[5+1]cyclization reaction of 2-arylanilines with diazo compounds was achieved.The optimized reaction conditions were determined by screening solvents,atmospheres,temperatures and diazo compounds.Under the identified reaction conditions,the scope of 2-arylanilines was evaluated.Using sulfonyl-derived diazo compounds as the coupling partners,17 examples of substituent-free phenanthridines were prepared by cleavage of C-C bond and C-S bond.Using ester-derived diazo compounds as substrates,15 examples of C6-carboalkoxy-substituted phenanthridines were obtained by cleavage of C-C bond.The experimental mechanism showed that the reaction underwent N-H insertion,SEAr,C-C cleavage and oxidative aromatization.This work realized the domino reaction using diazo compounds as Cl synthons through the structural control under metal-free condition,where phenanthridines and C6-carboalkoxy-substituted phenanthridines were prepared with highly chemical selectivity.(4)A[5+1]carbonylation of 2-vinyl/pyrrolylanilines with dioxazolones was established.The optimized reaction conditions were determined by screening solvents,temperatures and dioxazolones.Having established the optimal conditions,the scope of anilines was explored,both 2-vinylanilines and 2-pyrrolyanilines could apply to this carbonylation,and 22 examples of quinolinones and 16 examples of pyrrole-quinoxolinones were successfully synthesized with good yield(up to 92%yields).Based on the systemic experiments of mechanism,it was suggested that the reaction underwent Curtius-type rearrangement,formation of isocyanate and Prins-type reaction.This method realized the dioxazolones as a C1 coupling reagent participate in[5+1]carbonylation under metal-free condition,which provided a new idea for the preparation of quinolinone and pyrrole-quinoxolinones.