Construction Of Nitrogen-containing Fused Ring Compounds Via The Cascade Annulation Reaction Of O-enoyl Aryl Isonitriles

Acridine/acridinone and azepine derivatives,as important nitrogen-containing heterocyclic compounds,are widely found in plants and various marine organisms.They are key structural units of fluorescent dyes and fluorescent probe materials due to their unique planar polycyclic structure.In addition,these compounds are widely used as antibacterial,antimalarial and anticancer drugs in the pharmaceutical industry.Therefore,it is great of practical significance to explore a method for the efficient synthesis of acridine/acridone and azepine derivatives.Isonitrile compound is an important C1 synthon with a pair of lone pair electrons and a vacant orbital,which can be used as both a nucleophile and an electrophile.It has been widely studied in the fields of organic chemistry,pharmaceutical chemistry and polymer science.In the paper,acridine derivatives and azepine derivatives were synthesized by tandem reactions of functionalized isonitrile and unsaturated carbonyl compounds with base and Lewis acid catalyzed,which will have wide application prospect in biology and medicine.Firstly,a wide range of acridones and their cyclo[b]-fused derivatives are efficiently constructed by a double annulation of o-enoyl arylisocyanides with?,?-unsaturated carbonyls under simple metal-free condition.This protocol is general,efficient and practical,featuring the successive formation of two rings by a one-pot domino transformation.A tandem process involing an isocyanide-based[1+4]cycloaddition,an aminofuran-based intramolecular[4+2]cycloaddition,ring opening and aromatization is proposed for the transformation.Second,a wide range of azepine derivatives are efficiently constructed by tandem annulation of o-enoyl aryl isonitrile and?,?-unsaturated carbonyl compounds with Y(OTf)₃and Ti Cl₄ as catalyst.This protocol is general,efficient and practical,involing a series of steps of?nucleophilic addition-intramolecular cyclization-Friedel-Crafts reaction-electron transfer-water molecules nucleophilic attack-dehydrogenation proton?.Different from the traditional "6,7,6" system,the azepine derivatives features "6,7,5" ring system.