The Use Of Tandem Reactions To Construct The Class Of Nitrogen-containing Heterocyclic Compounds

It is well-known that the 1,2-dihydroisoquinoline,isoindole and isoquinoline rings are the most ubiquitous heterocyclic motifs and are found in many natural products and pharmaceuticals that exhibit remarkable biological activities.Significant effort continues to be given to the development of new 1,2- dihydroisoquinoline- or isoindole- or isoquinoline-based structures and new methods for their construction, due to their importance as substructures in a broad range of natural and designed products as well as synthetic intermediates in total synthesis of natural alkaloids. Although a number of protocols have been established to construct these compounds, the development of novel methodologies that allows the facile assmbly of substituded heterocycles from readily available starting materials remains an important objective. This dissertation is mainly foused on the tandem reactions for synthesis of 1, 2-dihydroisoquinoline,isoindole and isoquinoline rings.Firstly,we described copper(â… ) iodide catalyzed three-component reactions of 2-alkynyl benzaldehydes,amines,and diethyl phosphite,leading to the 2,3-disubstituted-1,2-dihydroisoquinolin-1-ylphosphonates.Isoquinolinium intermediate may be involved in the reaction process.We also described AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldehydes,amines,and sodium borohydride under mild conditions,which provide a facile and efficient protocol to facilitate the concise synthesis of 1,2-dihydroisoquinoline derivatives.Another novel and highly effective one-pot combination of AgOTf and proline catalysis for the synthesis of 1,2-dihydroisoquinoline derivatives via multicomponent reactions of 2-alkynylbenzaldehydes,amines,and ketones was disclosed as well.In addition,a combination of AgOTf and Yb(OTf)₃ as catalyst was demonstrated highly effective in the tandem cyclization-[3+3]cycloaddition reaction of 2-alkynylbenzaldoxime with dimethyl cyclopropane-1,1-dicarboxylate,which generated the tetrahydro-1,2-oxazine-fused 1,2-dihydroisoquinolines in good yield.Secondly,we investigaeted the palladium(â…¡)-or silver(â… )-catalyzed reactions ofα-amino(2-alkynylphenyl)methylphosphonate.We found that this metal-tuned reaction provide a novel and efficient route to 2,3-disubstituted-2H-isoindol-1-ylphosphonate or 2,3-disubstituted- 1,2-dihydroisoquinolin-1-ylphosphonate.Moveover,we realized the efficient synthesis of isoindol-1-ylphosphonate derivatives via Pd(0)-catalyzed reaction ofα-amino(2-alkynylphenyl) methylphosphonate with aryl iodide.Next,we disclosed a highly efficient and general method for the generation of functionalized isoquinoline N-oxides via sequential electrophilic cyclization/cross-coupling reactions of 2-alkynylbenzaldoximes with I₂,Br₂,NBS, NIS or ICI under mild conditions.Meanwhile,an unexpected generation of isoquinoline-based azomethine ylides starting from 2-alkynylbenzaldoximes,DMAD, and bromine via tandem electrophilic cyclization-[3+2]cycloaddition-rearrangement reactions was discovered.These products could be further elaborated by Suzuki-Miyaura couplings to introduce more diversity.We also described a highly efficient electrophilic cyclization of N'-(2-alkynylbenzylidene)-hydrazide with I₂,Br₂, or ICI in dichloromethane at room temperature.This reaction proceeds smoothly under extremely mild conditions,which provides a useful method for the synthesis of functionalized isoquinolinium-2-yl amides.Finally,the tandem addition-cyclization reactions of 2-alkynylbenzenamines with isothiocyanates catalyzed by silver triflate were investigated,and the desired 2,4-dihydro-1Hbenzo[d][1,3]thiazines was obtained in good yield.Meanwhile,the construction of 2-aminobenzothiazole was realized in copper(â… )-catalyzed tandem reaction of 2-iodobenzenamine with isothiocyanate under mild conditions.