One-step Construction Of Benzoxazepine And Fully Substituted Indole Derivatives From Tetrayne With Oxazolines

Benzyne intermediates play an important role in organic synthesis due to their high reactivity and unique reaction advantages.Heterocyclic compounds are cyclic compounds containing one or more heteroatoms,most of which have certain physiological activity and pharmacological value.Thus they have important applications in the fields of natural products,pharmaceutical molecules and functional materials.The main research content of this paper is that benzyne intermediates formed by tetrayne substrates through hexadehydro-Diels-Alder(HDDA)reaction,which are immediately captured by oxazoline compounds with different substituents to synthesize different types of heterocyclic compounds in one pot.1.Tetrayne and oxazoline reagents to construct benzoxazepine derivatives.We have studied in detail the reaction of the benzyne precursor tetrayne with oxazolines in which the substituent at the 2-position are alkyl and hydrogen,and a series of novel benzoxazepines and fused benzoxazepines derivative are synthesized.First,under the conditions of anhydrous oxygen-free argon,through the Sonogashira coupling reaction,we obtain tetrayne substrates with different substituents.Subsequently,the tetrayne substrate reacted with oxazoline in which the substituent at the 2-position was an alkyl group and hydrogen to obtain benzoxazepines and fused benzoxazepine derivative in one step under optimal conditions.The mechanism of this reaction is based on the HDDA reaction to form the benzyne intermediate,the addition reaction of benzyne intermediate into C = N,and subsequent proton transfer.2.Tetrayne and oxazoline reagents to construct fully substituted indole derivativesWe have studied in detail the reaction of benzyne precursor tetrayne with oxazoline substituted at the 2,4-position with phenyl,and a series of novel fully substituted indole derivatives have been synthesized.First,under the conditions of anhydrous oxygen-free argon,through the Sonogashira coupling reaction,we obtain tetrayne substrates with different substituents.Subsequently,the tetrayne substrate reacted with oxazoline substituted with phenyl group at 2,4-positions to obtain novel fully substituted indole derivatives in one step under optimal conditions.The reaction mechanism is based on the HDDA reaction to form benzyne intermediate,the addition reaction of benzyne intermediate into C = N,proton transfer,and finally the removal of a molecule of HCHO.Here we obtained benzyne intermediates by HDDA reaction and subsequent capture reaction occurs immediately.No catalysts and additives are required,and multiple chemical bonds are built in one step.This reaction is a good complement to the traditional synthetic method of benzyne intermediates,and benzyne generated thermally has expanded the scope of application of benzyne reactions to some extent.All the new compounds in this paper have been characterized by NMR,HRMS and IR,and some of them have obtained single crystal structure by X-ray diffraction.