The Synthesis Of Dihalides And Cyclic Compounds Based On Intramolecular Cyclization Of Alkynes

Alkynes are an important precursor in organic synthesis.Due to its unique structure and reactivity,it has important applications in the construction of natural products and drug scaffolds.How to realize the functionalization of alkynes efficiently and green has been a hot research topic for synthetic chemists.A variety of chemical structures can be constructed through functional group reactions of alkynes,which enrich the library of organic compounds and provid the possibility for high-throughput screening of pharmacologically active molecules.Carbon-halogen bonds,spirocyclic skeletons,and tricyclic skeletons are widely present in various natural products and pharmaceutical molecules.It is of great significance to develop simple and efficient synthetic strategies.In this thesis,the functionalization of ortho amide groups in alkynes and the functionalization of N-aryl propynyl amides were studied under metal-free catalysis.The main contents of this thesis are organized as follows:1.ortho-Amide-directed 2,4-dihalohydration of conjugated enynesIn this work,a NXS-mediated 2,4-dihalohydration of enynes is described.It has been proved that ortho-acetamide participated in this 2,4-halohydration process.45cases of products were synthesized.Mechanism studies show that an amide oxygen transfers into enynes to form a carbonyl of the products.One equivalent of water is incorporated into the ortho-acetamide group.The reaction proceeds smoothly with good functional tolerance and the yield is 52%-92%.Interestingly,the structural elaboration is also realized when NaBH₄ is employed,synthesized 5 products.The optimized conditions are:NXS（2.5 equiv.）,THF:H₂O（v/v,1:5）,room temperature.2.Study intramolecular cyclization of N-arylpropiolamideAfacileprotocolforthetunablesynthesisof10-hydroxy-1-azaspiro[4.5]deca-3,6,8-trien-2-ones and benzo[b]pyrrolo[2,1-c][1,4]oxazin-3-ones is described.Tricyclic products were synthesized in 5 cases and spirocyclic products in 16 cases.A tunable synthesis has been realized by the use of ZnBr₂/oxone and TBAB/oxone.The reaction proceeds smoothly with high efficiency and broad substrate scope.Mechanistic studies indicate that an N-protecting group-assisted ortho-trapping reaction is involved.In the transformation,the reaction undergoesα-addition,ipso-cyclization,and ortho-trapping of the resulting spirocyclic species.The optimized conditions are:（1）ZnX₂（1.1 equiv.）,oxone（2.0 equiv.）,MeCN:H₂O（v/v=4:1）;（2）TBAB（1.1 equiv.）,oxone（1.2 equiv.）,MeCN:H₂O（v/v=4:1）,room temperature.