| The 6,8-dioxabicyclo[3.2.1]octane(6,8-DOBCO),as a type of oxygen-containing bridged ring skeleton,is widely present in various natural products,such as insect pheromone,which generally has good biological activity and potential for medicine discovery.However,the construction of 6,8-DOBCO remains a challenging task due to its unique structure.Although various strategies and methods have been developed,several longstanding problems,including tedious multi-step synthesis,limited variation in starting materials,and poor stereoselectivity,have yet to be effectively addressed.Thus,the development of smart catalytic technologies and concise synthetic routes to prepare 6,8-DOBCOs from simple and variable substrates has important theoretical significance and practical value.In recent years,metal-organic catalysis has become an extremely important and efficient synthesis method.Based on the designed strategy of step-by-step synthesis of 6,8-DOBCO skeleton,we used the relay catalysis of palladium/phosphoric acid to construct the 6,8-DOBCO skeleton by using accessible vinylethylene carbonate and amine-substituted enone as the starting substrates.This metal-organo relay-catalyzed transformation probably proceeds through a sequential reaction of N-allylic substitution,inverse-electron-demand oxo-Diels-Alder cyclization and intramolecular ketalization.A series of pyrrolidine fused 6,8-DOBCOs are obtained with excellent yield and diastereoselectivity.The reaction mechanism was verified by control experiments and separation,identification of reaction intermediates.Subsequently,we further changed the starting substrate to o-amino chalcones to construct the tetrahydroquinoline 6,8-DOBCO backbone.The compatibility of catalysis system was also solved by the screening of Lewis acids.Finally,With the aid of palladium and halogen-bonding donor catalysts,another interesting 6,8-DOBCOs bearing a tetrahydroquinoline moiety were constructed by using VECs and o-amino chalcones to furnish a broad spectrum of via the same reaction pathway.It also provides an important method reference for the diversity construction of 6,8-DOBCO heterocyclic skeleton. |
