Polysubstituted 2-aminopyrrole Synthesis Via Gold-catalyzed Intermolecular Nitrene Transfer From Vinyl Azide To Ynamide

Homogenous gold-catalysis has received significant attention in the past decades,as the cationic gold catalysts can act as π-Lewis acids to activate various unsaturated C-C bonds.Thus,a variety of useful transformations were developed recently.Among them,the generation of a-oxo gold carbene from the reaction of alkynes and suitable oxidants,has been considered as a safe alternative approach to transition-metal carbenes intermediate.Because the use of toxic and explosive diazo compounds can be avoided.Interestingly,the generation of the analogue,such as a-imino gold carbene,has less been explored,despite of its potential synthetic application perspective in N-heterocycle synthesis.It is worthwhile to mention that since the first article on gold(I)-catalyzed intramolecular reaction of alkynes and organic azides done by Toste and co-workers in 2005,reports on corresponding intermolecular nitrene transfer are rare.Based on our previous work on gold-catalyzed polysubstituted pyrrole synthesis,we became interested in the gold-catalyzed intermolecular reaction of vinyl azides and ynamides,which eventually led to the formation of polysubstitued pyrroles.In this thesis,we would like to describe our efforts on this topic,mainly including three parts:(1)gold-catalyzed reaction of vinyl azides and ynamides;(2)the comparison of the reactivities between vinyl azides and 2H-azirines;(3)mechanistic studies.After extensive experiments,we obtained the optimal reaction condition:in presence of 3 mol%cationic gold catalyst(JohnPhosAu(MeCN)SbF6),60℃ in 1,2-dichloroethane(DCE),the reaction of vinyl azides and ynamides could give the corresponding polysubstituted pyrroles in high yields.We have also compared the different reactivity behavior between vinyl azides and 2/H-azirines.Control experiments indicated that 2H-azirine was generated in situ,and took part in the reaction spontaneously.In some specific cases,such as the alkyl substituted 2H-azirines could partly poison the gold catalyst.Based on our mechanistic studies,plausible catalytic cycles were proposed.