Copper-Catalyzed Regio-and Stereoselective Three-Component Coupling Of Allenyl Ethers With Gem-dichlorocyclobutenones And B₂pin₂

Multicomponent coupling reaction is an important reaction in organic chemistry,which has the characteristics of short steps and high synthesis efficiency.However,when there are many components with different activities in the reaction system,there are many side reactions and the chemo-,region-and stereoselectivity of the reaction are difficult to control.Cyclobutenones are a significant intermediate in organic synthesis and an important synthetic building block for the efficient construction of bioactive molecules.Due to the inherent ring-strain energy,such structures readily undergo selective ring opening reactions under different substrate types,reaction conditions and substituent positions.However,the traditional synthesis and structural modification of polysubstituted 4-membered ring natural products mostly occur between two components,usually accompanied by expensive catalysts,harsh reaction conditions,complex operation and low atom utilization.So,looking for a new method to achieve the synthesis and structural modification of multi-substituted 4-membered ring has been one of the important tasks of our chemists.Inspired by the previous work,we have successfully realized the region-and stereoselective three-component coupling reaction of allenyl ethers,bis(pinacolato)diboron and gem-dichlorocyclobutenones in the presence of CuCl/SIMes·HCl catalyst system to synthesize a series of polysubstituted cyclobutenones in one step.In the reaction,the Cu-B species were preferentially inserted into the allene due to the different activity of unsaturated compounds allenyl ether and gem-dichlorocyclobutenone,and the alkyl copper intermediates were obtained.Then,the alkyl copper intermediate and gem-dichlorocyclobutenone with weaker activity were subjected to SN2’ reaction to overcome the problems of regionand stereoselectivity in a reaction system.The traditional functional group modification of polysubstituted 4-membered ring compounds mostly occurred between two components,which had the problems of expensive catalysts,harsh reaction conditions and low synthesis efficiency.The method could simultaneously modify the functional group of polysubstituted 4-membered ring compounds in the process of realizing the bifunctionalization of allenes,and had the advantages of simple substrates,cheap catalyst,high region-and stereoselectivity,high conversion efficiency,and atom economy.Compared with the conventional allyl-substituted linear electrophiles,we successfully applied cyclic allyl gem-dichloride as an electrophile to the threecomponent coupling allylboronation reaction.It has potential significance for the subsequent development of other cyclic allyl electrophiles to synthesize compounds with specific structural fragments.