Diastereoselective Synthesis Of Multisubstituted Dihydrofurans Via Multicatalysis Of O-Alkenyl-Substituted Cyanohydrins

As widely existed units in natural products and drug molecules,the substituted 2,3-dihydrofurans are treated as useful synthetic building blocks in the preparation of highly functionalized tetrahydrofurans and other heterocyclic compounds.However,it remains in great demand and a challenge for chemists to explore an efficient method to construct polysubstituted dihydrofurans with high diastereoselectivity from simple and cheap chemical reagents.The multicatalytic reaction as a synthetic methodology in constructing molecules has aroused the attention of researchers because of its efficiency and atom economy.At present,the application range of multicatalytic reaction is limited,and it is of great significance to develop the reactions with better reaction compatibility,readily available raw materials and widely applicable products.The cyanohydrins,as synthetic building blocks,are versatile intermediates for many pharmaceuticals and agrochemicals and also have considerable potential in organic synthesis.Based on the disadvantages mentioned above,we developed a type of multicatalytic reactions by the aid of Lewis base catalysts,using the O-alkenyl-substituted allylic cyanohydrins as substrates,to prepare multi-substituted 2,3-dihydrofurans with quaternary and tertiary carbon centers in a high diastereoselectivity by integrating allylic alkylation with intramolecular alkenylcyanation/1,4-addition of activated alkene in one pot.This thesis includes three parts:In the first part,we introduced the applications and syntheses of the 2,3-dihydrofurans,the reaction types and practical applications of the multicatalytic reactions and the applications of cyanohydrins.In the second part,O-alkenyl-substituted allylic cyanohydrins was prepared in high yields via a Lewis base-catalyzed allylic alkylation of Morita–Baylis–Hillman(MBH)carbonates and O-alkenyl-substituted cyanohydrins.Subsequently,we applied these new compounds in constructing the multisubstituted 2,3-dihydrofurans,incorporating contiguous quaternary and tertiary carbon centers by a Lewis base-catalyzed intramolecular alkenylcyanation/1,4-addition of activated alkene from the prepared O-alkenyl-substituted allylic cyanohydrins.The target products were obtained under optimized conditions with excellent yield and good diastereoselectivity.In the third part,we have developed an unprecedented one-pot cascade sequence(allylic alkylation/1,4-addition cascade sequence)for the diverse synthesis of polysubstituted 2,3-dihydrofurans without isolation and purification of intermediates.Based on these results,we developed a method to synthesize polysubstituted 2,3-dihydrofurans diastereoselectively by using multicatalytic reaction catalyzed by a Lewis base-catalyst.Through the investigation of the reactivity of different substrates,it proved that the method has wide substrate scope,and the possible reaction mechanism is proposed based on a series of control experiments.