Rhodium-catalyzed [4+3] Annulation Of Indole Derivatives With N-sulfonyl-1,2,3-triazoles And Total Synthesis Of(±)-Aurantioclavine

Azepino[5,4,3-cd]indole skeleton,composed of three cycles,is often found in some indole alkaloids.Most of the natural products with this skeleton have significant cytotoxic activity and insecticidal activity.Therefore,it is of great significance to develop a fast and simple way to synthesize azepino[5,4,3-cd]indole skeleton.In recent years,N-sulfonyl-1,2,3-triazole has been widely used in organic synthesis.and that’s the reason why we studied this simple raw material.N-sulfonyl-1,2,3-triazole can synthesizeα-imine metal carbene through diazoimine intermediates under the catalysis of transition metals.With its special characteristics（carbene carbon has electrophilic,and the imine nitrogen has a nucleophilic nature）,this metal carbene occurs in many types of reactions,for instance:insertion reaction,cyclopropanation,formation of Ylide reaction,etc.It is found that azepino[5,4,3-cd]indole skeleton can be obtained by the[4+3]cyclization reaction with carbene as the aza-[3C]synthon and the appropriate indole derivative as the[4C]synthon.Considering that the azepino[5,4,3-cd]indole skeleton is quite analogous to the natural product（±）-Aurantioclavine,we conducted a study on the total synthesis of natural product（±）-Aurantioclavine.That lays a solid foundation for this paper.By numerous experiments,we discovered that under the protection of nitrogen,1.5 eq of indole derivatives,with 1 mol%Rh₂（OAc）₄ as a catalyst and chloroform as a solvent,refluxed at 85 ^oC for 4 h,and then add 1 eq of PPTS to the reaction in room temperature.After 30 minutes,the product was obtained with a yield of 99%.During our experiments,we found that this reaction take place smoothly when the indole N bear an electron-donating group or hydrogen（especially a high yield with electron-donating group）.But there is on reaction when the electron-withdrawing group on the indole nitrogen.Afterwards,we tried to synthesize the natural product（±）-Aurantioclavine,using a special 4-nitrogen-substituted triazole as a substrate,and then synthesize the corresponding tricyclic compound by appropriately improving the above-mentioned optimal conditions.Then,the natural product（±）-Aurantioclavine was synthesized by a simple three-step reaction:removing Phth protecting group,removing NH₂,and removing Ts.Eventually,the natural product（±）-Aurantioclavine was synthesized rapidly by a four-step method with simple raw materials:N-sulfonyl-1,2,3-triazole and indole derivatives.It provides a more economical and convenient method for the synthesis of the natural product（±）-Aurantioclavine and its analogues.