Synthesis Of Polycyclic Indole Derivatives By Indium Catalyzed Prins/Friedel-Crafts Tandem Cyclization

Prins cyclization is a highly efficient method for constructing heterocyclic compounds with different ring sizes,which involves the condensation and cyclization of aldehydes and homoallyl alcohols under the catalysis of acids.Due to the formation of carbon cation during the reaction process,it can be used as an initiator for the cascade process.The carbon cation can be captured by aryl nucleophilic reagents and undergo intramolecular Friedel-Crafts reactions,which can effectively construct polycyclic systems and provide facile access to the core structures of complex pharmaceutical active molecules and natural product structures.This thesis mainly focuses on the study of the Prins/Friedel-Crafts tandem cyclization reaction of indolealdehyde with homoallylic alcohols,constructing a series of polycyclic fused indole.The resulting polycyclic skeleton exists in a variety of natural products and bioactive compounds.By means of systematically optimization of reaction conditions,it was found that using 10 mol%In（OTf）₃ as the catalyst,dichloromethane as the solvent,the homoallyl alcohol and indole aldehyde at a feeding ratio of 1.2:1,and reacting at 30℃for 12 hours were the optimal conditions for the reaction.Finally,the target products could be obtained in up to 98%yield and excellent diastereoselectivity（>95:5 dr）.The method is practical which could work well under mild conditions with broad substrate scope（30 examples）.Subsequently,we designed and synthesized 3novel tetra-nitrogen chiral oxazoline ligands,which were employed in the asymmetric version of the Prins/Friedel-Crafts tandem cyclization reaction.This study provides new thoughts and methods for the synthesis of important natural products containing polycyclic fused indole skeletons.