Generation Of Donor/Donor Copper Carbenes Through Copper-Catalyzed Diyne Cyclization

Catalytic transformations involving metal carbenes are arguably the most important aspect of homogeneous transition metal catalysis.Over the past decades,organic chemists have achieved various methods for the generation of metal carbenes from readily available alkynes,which played an important role in metal carbene chemistry.Importantly,the generation of metal carbenes from alkynes avoids the use of hazardous,potentially explosive diazo compounds.Therefore,the field has become a conspicuous area in alkyne chemistry due to its novel properties and reaction modes.However,most of these transformations are limited to the use of noble-metal catalysts and successful examples of such an asymmetric version are still very scarce.Transition metal-catalyzed cascade cyclizations of 1,n-diynes(n=3,4,5,6,7,etc.)have proven to be a practical method for the rapid construction of various structurally complex cyclic compounds due to their high bond-forming efficiency and atom economy.Nevertheless,non-noble metal-catalyzed tandem cyclization of diynes,especially those based on asymmetric versions,were rarely reported so far.Based on our previous work in ynamide chemistry,the content of thesis is that we studied the generation of metal carbenes via diyne cyclization.In addition,we took advantage of the special reaction properties of ynamide to design non-noble metal-catalyzed cascade cyclizations of 1,5-diynes,and to realize asymmetric versions based on the above research.Main contents of this thesis include the following three sections:In the first part,we introduced the research backgrounds based on comprehensive survey of the literature,general methods for the generation of gold carbenes from alkynes;the formation of donor/donor metal carbenes via transition metal-catalyzed enynal/enynone cyclization;transition metal-catalyzed cascade cyclizations of diynes,including the asymmetric cyclization;the reactive nature and its application of ynamides.Therefore,we proposed research outlooks and targets after summarizing the research background.In the second part,we developed an efficient copper-catalyzed enantioselective tandem reaction of 1,5-diynes via intramolecular cyclization-initiated cyclopropanation and C-H insertion reaction,enabling the construction of chiral tetracyclic or tricyclic pyrrole compounds,respectively.Moreover,a series of mechanistic studies revealed that the generation of donor/donor copper carbenes is presumably involved in this 1,5-diyne cyclization,which is distinctively different from the related gold catalysis.Importantly,this protocol provides a novel way for the generation of donor/donor metal carbenes via non-dizao approach.Finally,we proposed a plausible mechanism for this reaction.In the third part,we developed a non-noble copper-catalyzed enantioselective reaction of alkenyl N-propargyl ynamides with alkenes by formal[3+2]cycloaddition based on the second part.This method allows assembly of diverse chiral pyrrole-fused bridged compounds with excellent enantioselectivities(up to>99%ee)and diastereoselectivities(d.r.>50/1).This annulation could also be extended to late-stage functionalization of active molecules or natural products that contain styrene moieties,which could further prove its potential synthetic utility.Moreover,mechanism studies revealed that the alkenyl moiety is essential for this reaction to form the Cu-containing all-carbon 1,3-dipole intermediates.Importantly,this protocol provides a novel way for the formation of metal-containing 1,3-dipoles via non-dizao approach.Finally,we proposed a plausible mechanism for this reaction.