Metal-catalyzed Radical Tandem Cyclization Toward The Synthesis Of Indolo-[2,1-a] Isoquinolines

Indolo-[2,1-a]isoquinolines have invaluable biological activity and pharmacological potential,which are found in a wide range of synthetic drugs,natural products,and various functional materials.In this paper,we explored the synthesis of indolo-[2,1-a]isoquinoline tetracyclic skeletons in one pot via tandem radical cyclization.This paper consists of the following four parts.ChapterⅠIn this chapter,recent progress on nitrogen center radicals included reaction were summarized.We discussed the current research on the generation of nitrogen center radicals ranging from indirect methods,direct oxidation of the N-H bond,the cleavage of weak N-X bond.In addition,we provided a detail explanation of the application of nitrogen center radical tandem cyclization reaction in synthesis.Chapter IIIn this chapter,we reported a nitrogen radical tandem cyclization to construct the core tetracyclic skeletons of indolo-[2,1-a]isoquinolines in one-pot.With Cu SCN as catalyst,O-benzoyl hydroxylamine as a nitrogen source to generate nitrogen radical via single eletron transfer progress,then cyclize with 2-arylindoles to provide a range of functionalized indolo-[2,1-a]isoquinoline derivatives in good to excellent yields.Chapter IIIIn this chapter,we use cyclobutanol derivatives as radical precursors,and Mn（OAc）₃.2H₂O as catalyst to promote cyclobutanol to generate carbon radical from ring-opening then further finish cyclization with 2-arylindole to synthesize indole indolo-[2,1-a]isoquinoline derivatives.The reaction obtained the target products under mild conditions with good yields.Chapter IVIn this chapter,we describe on the conclusions and prospects of this article.We have successfully completed the construction of a series of indole derivatives via radical tandem cyclization reactions.We hope that more complex natural products can be synthetized through this strategy.