Research On The Construction Of Tetrahydropyridazines And 1H-Indenes Via Catalytic Annulation Reactions Of Metal Carbenes

Metal carbene,which commonly generated from the diazo compounds,is one of the versatile intermediates in organic synthesis,and plays a critical role in the construction of complex molecules due to its versatile reactivity.Particularly,metal carbene shows advantages in the construction of diverse polycyclic compounds through various cyclization reactions.This paper mainly studied catalytic carbene cyclization reactions with different accessible carbene precursors such as enoldiazoacetates and conjugated enynones,which aimed at the develoment of novel carbene transformations and construction of polyocyclic heterocycle with structural diversity.Part I:Catalyst-dependent[4+2]-cycloaddition reactions of azoalkenes from a-halohydrazones with enoldiazoacetates have been developed,which provide a general access to tetrahydropyridazines and tetrahydrodiazepine.Mechanistically,treatment of a-halo N-acylhydrazone with base would afford azoalkenes in situ,which upon treatment with enol diazoacetates or in-situ generated cyclopropenes would facilitate an intermolecular[4+2]cycloaddition reaction to offer the tetrahydropyridazines.Part Ⅱ:This part has disclosed an unprecedented copper-catalyzed intramolecular cascade cyclization reaction of conjugated enynones that provides an expeditious synthesis of substituted 1H-indenes.Notably,detailed mechanism experiments and DFT calculations have been carried out to elucidate that the enynones underwent a copper-mediated 5-exo-dig cyclization to afford copper-(2-furyl)-carbene intermediate,followed by diene-carbene cyclization(one step but involving 67c cyclization of Cu-carbene and reductive elimination)and 1,5-hydrogen shift to give the 1H-indenes.