Study On The Reactions Of N-tosylhydrazones In Copper Systems

The development of new methods for the efficient construction of molecular scaffolds with simple,inexpensive and readily available reaction materials through simple reaction conditions and reaction steps is one of the challenging research topics in organic synthesis,among which,how to achieve the precise control of conversion,selectivity and synthetic step in the reaction is a higher requirement for organic synthetic chemistry.As a common catalyst,copper salt not only has the advantages of rich source,low price and low toxicity,but also exhibits unique chemical selectivity and reactivity in organic synthesis.Meanwhile,N-tosylhydrazones are kind of readily available and versatile substrates,which can be served as safe and stable diazo compound precursors.Therefore,to develop diversified transformation reactions based on N-tosylhydrazones in copper reaction systems is of great theoretical significance and application value.In this subject,we developed a series of new methods for organic synthesis with high efficiency,high selectivity,and step-economy using N-tosylhydrazones or alkyne as substrates,including cyclization,cross-coupling,difunctionalization are multi-component cyclization,accessing successfully to multiple molecular skeletons.This research has not only developed the synthesis methodology of copper-catalyzed reactions,but also enriches the research content of hydrazones chemistry,and has important research significance and clear application prospectsThis project has developed series of new methods for the construction of multiple molecular skeletons such as polysubstituted furans,arylnitriles,sulfur-substituted quaternary carbons,and substituted benzothiazoles with N-tosylhydrazones or alkyne as the research object under a copper reaction systems.It involves chemical bonds selective cleavages and new chemical bonds efficient reorganizations,including the formation of C-C bonds,C-N bonds,C-O bonds and C-S bonds.The specific research content includes the following five parts:In chapter two,we have achieved a copper-mediated[3+2]oxidative cyclization reaction to afford 2,3,5-trisubstituted furans in moderate to good yields,which is the first implementation of utilizing N-tosylhydrazones as two-carbon synthons.The features of this method include inexpensive metal catalyst,readily available substrates,high regioselectivity and convenient operation.In chapter three,employing thiocyanate as source of cyanide,we have achieved a copper-catalyzed cyanation of N-tosylhydrazones accessing to racemicα-aryl nitriles in high yields.The employ of inexpensive copper catalyst,eco-friendly oxygen,readily available starting materials,simple operation conditions,and the regeneration of“CN”sources from low-toxic thiocyanate salts have presented a novel and safe protocol for the synthesis ofα-aryl nitriles.In chapter four,we have developed a copper-catalyzed cyanothiolation of N-tosylhydrazones with thiocyanates to incorporate sulfur-substituted quaternary carbon center.This novel protocol involves the procedure of copper carbene species promoting S-CN bond cleavage and C-CN/C-S bond reconstruction to introduce both sulfur and cyano groups in a single carbon center,and has synthesized diverseα-arylthioalkanenitriles with high yield and selectivity.In chapter five,we have achieved a copper-promoted[3+1+1]-type cyclization reaction to construct 2-substituted benzothiazoles with high selectivity from o-iodoaniline derivative,S₈and N-tosylhydrazone.In the protocol,by changing the reaction system,the carbon atom on N-tosylhydrazone is used selectively as a binding site to achieve the construction of multiple carbon-heteroatom bonds.In chapter six,we have achieved a copper catalyzed multi-component tandem cyclization to achieve the controllable assembly of benzothiazole derivatives from o-haloanilines,elemental sulfur and terminal alkynes.In this protocol,C≡C triple bond is used as one-carbon synthon,and C atoms on the C≡C triple bond are controllably involved in the construction of C=N and C-S bonds in different reaction systems.It is worth noting that H₂O is confirmed to provide hydrogen atoms through the deuterium-labeling experiments.