Synthesis Of Piperidine Derivatives By Tandem Reaction Based On ?-Rhodium Carbene Imide Intermediate

As a very important reaction intermediate in the field of organic synthetic chemistry,metal carbene can be used in the synthesis of many compounds by achieving selectivity controlled reactions which are difficult to achieve.It has a wide range of applications in material and pharmaceutical chemistry.In recent years,there have been a lot of reports about reactions of metal carbene in organic synthesis,which formed by diazo compounds and various metals such as Rh,Au,Cu,Pd etc.The metal carbene intermediates can realize cycloaddition,insertion,rearrangement,migration coupling,formation of ylide reaction,etc.1,2-migration is one of the rearrangement reactions,including hydrogen,aryl,alkyl,ester group,sulfur and nitrogen migration etc.,which can construct many organic molecules that are difficult to complete in other reactions.In this paper,there was a 1,2-migration of ester-group in the1-sulfonyl-1,2,3-triazole through rhodium carbene intermediate and was performed to obtain azadiene,which was then reacted with electron-rich vinyl ether to form piperidine by polarity reversal Diels-Alder reaction.In this paper,we obtained piperidine through Diels-Alder reaction with n-butyl vinyl ether and aza-diene which generated from rhodium carbene by 1,2-migration of ester-group.To improve the yield of product,we adjusted different reaction factors and found the optimum reaction condition is:under nitrogen protection,triazole and n-butyl vinyl ether with 1:3 equivalent ratio under the catalysis of Rh₂?OAc?₄?2mol%?with toluene as reaction solvent at 80^oC,the reaction yield can reach 87%.Subsequently,we expanded the substrates of the reaction in 1,2,3-triazole and vinyl ether respectively,then found that the reaction could be compatible with many kinds of different substituents.The product piperidine is an important structural fragment of alkaloids with biological activity,and can be used for hydrolysis,substitution,coupling and other derivative reactions to synthesize other organic molecules.