Copper-catalyzed ?-substituted Alkenyl Azide [3+2+1] Cyclization And Aldol Reaction

Alkenyl azides are special conjugated structure formed by the direct connection of olefins and azides.The close interaction between the two functional groups lead vinyl azides to exhibit a unique high reactivity.Among the numerous alkenyl azides7 types,the a-substituted alkenyl azides are extremely reactive,it can undergo Schmidt rearrangement reaction with electrophiles,it can react with nucleophile to form imine anions and also can act as free radicals and metal enamine free radicals to react.In the various reaction processes described above,the a-substituted alkenyl azides have involved as key ternary synthons or binary synthons,but it has not been reported that the a-substituted alkenyl azides have acted as ternary synthons and binary synthons in one-pot reaction.Based on the highly reactive sites of ?-carbon in a-substituted alkenyl azide compounds,a-substituted alkenyl azides can also be used to prepare important organic molecides by a series of ?-carbon functionalization reactions,but so far the researchs are not enough to be further studied.In response to the above research questions,the specific research of this paper is as follows:1)Copper-catalyzed regioselective cyclization of ?-substituted vinyl azides by gem-difluoromethylene for trisubstituted pyridines.We have developed the[3+2+1]tandem cyclization reaction between a-substituted alkenyl azides and difluoromethylene compounds catalyzed by monovalent copper.It has achieved that the a-substituted alkenyl azides act both as ternary synthons and as binary synthons in a one-pot reaction,it has expanded the strategy of difluoromethylene as non-fluorinated one-carbon synthons at the same time,It has established highly efficient,convenient,and highly regioselective synthesis of polyfunctionalized trisubstituted pyridines.2)Copper catalyzed aldol reaction of a-substituted alkenyl azide with trifluoroacetophenone.We have developed a new method for the aldol condensation reaction of copper-catalyzed a-substituted alkenyl azides and trifluoroacetophenones,which extends the type of ?-carbon functionalization in ?-substituted alkenyl azides.It establishes a new reaction based on this inexpensive and readily available ?,?,?-trifluoroacetophenone as a fluorinating reagent to achieve ?-substituted alkenyl azides ?-carbon functionalization,and it also provides a new preparation route for the direct synthesis of ?-trifluoromethyl-?-hydroxy-1,2-diphenylacetone compounds.