Synthesis Of Aza-Heterocyclic Compounds Through Palladium-catalyzed Cycloisomerization Reactions

Multi-substituted aza-heterocyclic compounds are of great significance in natural products and medicines,and thus have received widespread attention from the synthetic organic chemists.Palladium-catalyzed cascade cycloisomerization reaction is a good tool for the rapid synthesis of substituted aromatic molecules.In this paper,we firstly utilized the palladium and norbornene promoted Catellani reaction as a synthetic strategy,successfully constructed the eight-membered heterocyclic skeleton of benzosulfur nitrogen with"three-dimensional"spatial structure.In addition,we disclosed the usage of isocyanide as a C1 building block to prepare novel indole derivatives through palladium-catalyzed cascade insertion/cyclization reactions.This paper is divided into three parts.The first part of the paper summarized the latest research progress of Catellani reaction.Based on the classified electrophilic reagents that participated in the termination steps of Catellani reaction,this section briefly introduced the recent research progresses of different terminal reagents,such as alkylation reagents,arylation reagents,amination reagents and acylation reagents.Moreover,the research results of norbornene worked as the substrate that participated in Catellani reaction to construct the carbocyclic skeleton,and the norbornene-assisted meta-C-H activation reactions,were also demnonstrated.In the second part of the paper,the use of ortho-substituted NH-sulfonimide and norbornadiene?NBD?as the substrates,?4-FC₆H₄?₃P as the ligand,and Pd?dba?₂ as the catalyst to promote the tandem cyclizations were reported.A series of novel iminosulfonyl derivatives which containing sulfur-nitrogen eight-membered heterocyclic structures were prepared under the carefully modified reaction conditions.It was found that dba as an important extra additive can effectively inhibit the formation of by-products.Under these conditions,the expected iminosulfone heterocyclic derivatives containing benzo eight-membered rings were synthesized in moderate to excellent yields.In the third part,the palladium-catalyzed cyclization reactions of o-iodo-alkenyl arylamine with isocyanides were developed.Several novel types of indole derivatives with special structures were synthesized efficiently and selectively.Mechanistically,the cyclization reactions in the conversion were accomplished through some important consecutive steps,which involving oxidative addition of low-valent Pd⁰-species,regioselective addition of alkenyl groups,1,1-insertion of isocyanate,and?-H eliminations.