Synthesis Of Nitrogen-containing Heterocycles Via Annulations Of Alkynes

It is well-known that the nitrogen-containing heterocyclic compounds are the largest class of organic compounds.Because of their unique structure and properties,the nitrogen-containing heterocycles play a crucial role in many chemical areas.As one of the most important nitrogen-containing heterocyclic compounds,oxindoles and indoles are widely existed in nature,and many of which have the physiological activity and biological activity.Therefore,the development of practical and efficient methods for the synthesis of nitrogen-containing heterocyclic compounds has been a research hot-topic in organic synthesis.The cyclization reactions have become one of the most powerful and straightforward tools in synthesis because of their highly efficiency and atom-economic manner for the construction of the cyclic compounds.In recent years,considerable efforts have been focused on the application of the cyclization reactions in the synthesis of a lot of nitrogen-containing heterocyclic compounds.Cascade reactions represent important and useful synthetic methods in organic synthesis,which have widely application in medicinal chemistry and materials science.Due to its simply,highly atom economy and environment friendly,the cascade reaction is has made a rapid progress in synthetic chemistry.This dissertation mainly focuses on the construction of nitrogen-containing heterocyclic compounds through the cyclization reactions of N-arylpropiolamides and the cascade reaction of ynamine with terminal alkynes,1,3-dicarbonyls and amines.This dissertation is divided into six parts.In chapter 1,recent progress in the construction of nitrogen-containing heterocyclic compounds is summarized in detail.The chapter mainly focused on the synthesis of spiro[4.5]trienones,1,2-oxazines,2-alkynyl indoles,2-amido-indoles and 3-alkenyl indolin-2-ones.In chapter 2,a novel and direct oxidative spirocyclization of arylpropiolamides with t-BuONO?tert-butyl nitrite?leading to 3-nitro azaspiro[4,5]trienones has been developed under metal-free conditions.This reaction involves the oxidative difunctionalization of alkynes initiated by a radical attack pathway using t-BuONO?tert-butyl nitrite?together with water as the nitro source and using TEMPO[?2,2,6,6-tetramethyl-piperidin-1-yl?oxyl]as the initiator,and provides a new example of oxidative alkyne difunctionalization via the formation of C-N/C-C bonds to access nitroalkene unit-containing spirocycles.In chapter 3,a metal-free radical-mediated[4+2]annulations of internal arylalkynes with t-BuONO?tert-butyl nitrite?is presented for the synthesis of benzo[e][1,2]oxazin-4-ones via the addition of t-BuONO across the C-C triple bond,hydration,isomerization and aromatic C?sp2?-H oxidation cascades.The ¹⁸O-labeling experiment proves that two oxygen atoms in the product system are from water.In chapter 4,new cascade reactions of N-allyl-N-??2-bromoaryl?ethynyl?amines with a wide range of nucleophiles,including terminal alkynes and 1,3-dicarbonyls,toward2,3-disubstituted indoles has been described by means of the Cu catalysis.This cascade cyclization method has a broad substrate scope with respect to the substituents,and allows three new chemical bonds formation in one-step leading to the five-membered-ring systems through release of HBr as the only accompanying product.Besides,the significance of the2-alkynyl indoles skeleton as a structural unit would render this method attractive for both synthetic and medicinal chemistry,thus paving the way for the synthesis of other complex biologically active heterocyclic systems.In chapter 5,a new,efficient protocol for 2-amido-indoles synthesis by copper-catalyzed cyclization of N-allyl-N-??2-bromoaryl?ethynyl?amines with amines was established.The method enables the formation of three chemical bonds in a single reaction through a sequence of aza-Claisen rearrangement,nucleophilic addition,Ullmann C-N coupling and cyclization,and represents a step-economical entry to 2,3-disubstituted indoles.In chapter 6,a new,mild route for the assembly of 3-alkenyl indolin-2-ones is illustrated that proceeds via a room-temperature palladium-catalyzed intramolecular oxidative aminocarbonylation of alkenes with amines and CO.This reaction represents a new aminocarbonylation strategy by employing an oxidative functionalization of a vinyl C?sp²?-H bond.