Study On The Construction Of Furo[3,2-C]coumarins And Indolizines By Alkenes And Alkynes

Heterocyclic compound exists in many natural products,which is one of the most active research content in the organic chemistry field.Five-membered heterocyclic compounds is a very important branch of all the heterocyclic compound and are important organic chemical industry raw materials and intermediates,widely used in pharmaceuticals,pesticide,dye chemical,biology,etc.Alkenes and alkynes are important staple product of petrochemical and peteoleum industries.And they are also cheap chemical raw materials.In this context,we described the construction of five-membered heterocyclic compounds from readily available alkenes and alkynes.(1)Furocoumarins are a structural motif found in numerous pharmaceutically active compounds.For this reason,considerable efforts have been expended to develop the synthetic methods of furocoumarins.An atom-economical,straightforward,convenient,and high regioselective route to synthesize furocoumarins with basic chemical materials is still highly attractive.To the best of our knowledge,the palladium-catalyzed synthesis of furo[3,2-c]coumarins directly from simple alkenes and 4-oxohydrocoumarins has not been reported so far.As a result of development on the transition-metal-catalyzed C-H functionalization of alkenes in our group,herein,we developed a Pd(CF3COO)2 catalyzed aerobic oxidative alkoxylation of 4-oxohydrocoumarins and alkenes in a cascade sequence to afford the desired furo[3,2-C]coumarins in good yields.Both aryl-substituted internal alkenes and terminal alkenes produced high yields of furo[3,2-c]coumarins under the optimized conditions.Atom-economical characteristics and mild conditions of the method are in accord with the concept of modern green chemistry.Future study on furo[3,2-C]coumarins show promising fluorescence quantum yields and cancer growth inhibition.(2)Indolizines and their derivatives,which exhibit intriguing molecular structures featured by an N-bridgehead bicyclic ring system fused with both a π-excessive pyrrole and a π-deficient pyridine,have been employed as an important basic building block in a wide range of natural products and pharmaceuticals.Many indolizines have shown important biological activities.As a result,different synthetic methodologies for indolizines have emerged.During the past few years,direct benzylic C-H functionalization of 2-alkylazaarenes has attracted much attention.To the best of our knowledge,no examples of synthesis of indolizines from simple alkynes through C-H functionalization of 2-alkylazaarenes,have ever been reported.Herein,we firstly describe a silver-mediated C-H bond activation of 2-alkylazaarenes with both terminal and internal alkynes for the formation of indolizines under mild conditions.From the synthetic point of view,this protocol represents an extremely simple,efficient way to construct substituted indolizines from basic starting materials.The crystallization of indolizine compound from ethanol gave a single crystal suitable for X-ray analysis.A deuterium labeling experiment gave us some information about the reaction pathway.The terminal alkynes and internal alkynes follow different paths to affords the final indolizine products.Thus it complements the method for the rapid formation of multifunctional nitrogen-containing heteroaromatic molecules.