Approach To N-/O-Heterocycles Based On Reactions Of The Trapping Of Active Intermediates Generated From Metal Carbene

Metal carbene reactions represent a powerful tool in modern organic synthesis,allowing for the rapid assembly of complex structures that cannot be readily realized with other methods.A variety of metal catalysts have been reported to mediate these reactions with diazo compound as the carbene precursor,including rhodium,copper,palladium,gold,silver,iron,etc.In the past few decades,the in situ trapping of active intermediates derived from metal carbenes has emerged as an efficient strategy for the development of a variety types of multi-component reactions(MCRs).In this context,our research group has developed a series of MCRs for the rapid construction of polyfunctional molecules via electrophilic trapping of metal carbene-derived ylides or zwitterionic intermediates.In view of the step-economic feature as well as the efficiency leading to heterocycles with structural complexity,the pursuit of new types of MCRs based on in situ trapping of active intermediates is highly sought after.In this thesis,we have explored three types of MCRs with the strategy of the trapping of metal carbene species or ylide intermediates with different electrophiles to construct heterocyclic compounds.Trying to find the new electrophiles,we found that the alkyl copper intermediate can be intercepted by nitrosoarenes which have served as both O-and N-based electrophiles in an array of reported transformations.About the new carbene precursors,the pyridyl carbene intermediates generated in situ from pyridotriazoles can be used in our MCRs.By these methods we synthesized 5-(trifluoromethyl)-2,5-dihydroisoxazole and 2-pyridyl 2,5-dihydrofuran derivatives.And these obtained products could be transferred to 1,4-oxazepine derivatives under gold catalysis.In chapter 2,we discovered a Cu(I)-catalyzed three-component reaction of terminal alkynes,trifluoromethyl diazo compounds and nitrosoarenes.This transformation is proposed to proceed through an electrophilic trapping of the copper carbene species generated from terminal alkynes and diazo compounds by nitrosobenzenes.With this method under mild reaction conditions,a series of trifluoromethyl-substituted dihydroisoxazoles were synthesized in one single step with high efficiency.In chapter 3,we described a Rh(II)-catalyzed [4+1]-cycloaddition of pyridotriazoles and propargyl alcohols,which provides a direct access to 2-pyridyl substituted 2,5-dihydrofurans in moderate to high yields under mild reaction conditions.Mechanistic investigations revealed that the oxonium ylide is the key intermidiate in this transformation,which was trapped successfully through Mannich type addition with external imine.In chapter 4,we have further explored the Mannich type addition that was discover in the previous chapter.We have successfully developed an enantioselective three-component reaction of alcohols,pyridotriazoles and ethyl glyoxylate imines,as well as a four-component reaction of alcohols,pyridotriazoles,anilines and ethyl glyoxylates in the presence of Rh(II)catalyst and chiral Br?nsted acid.Polyfunctional molecules have been synthesized in high regio-and enantioselectivities from simple and readily avaiable materials by this multicomponent reaction.