Construction Of Multifunctional Aryltetrahydronaphthalene Derivatives From Tetraynes And Lovastatin By Coupling Reaction

The HDDA(Hexadehydro-Diels-Alder)Reaction provides a powerful method for constructing new carbon-carbon bonds and has played an important role in the synthesis of many complex molecules.With the deepening of the research on HDDA Reaction,the use of benzyne intermediates in organic synthesis has become more and more extensive.The participation of benzyne intermediates in the construction of natural product skeletons has become a hot spot for chemists.In this paper,in the absence of catalyst and no protective gas,the HDDA reaction of tetrayne derivatives with different substituents(p-~n Pr,p-Cl,p-Me,m-Me)and lovastatin was studied.Through the process of benzyne intermediates,simultaneously forms carbon-carbon bonds,the aryltetrahydronaphthalene derivatives could be constructed by one-step conveniently.The reaction could more easily occurred under the temperature of110?without any catalyst involved by optimizing the conditions.This approach requires no directing groups but exhibits excellent stereoselectivity.Under optimal conditions we have generated 31 polycyclic compounds with aryltetrahydronaphthalene skeleton structure.All products were characterized by IR?NMR and HRMS.One of the products was confirmed by X-ray single crystal structure analysis.The possible mechanism of the reaction was proposed:The benzyne intermediates is obtained by cyclization of tetrayne,and then reacted with lovastatin by Alder-Ene to obtain aryltetrahydronaphthalene derivatives.Because of the space effect of lovastatin,the reaction has stric-stereoselectivity.We found that the substituents on the tetrayne substrate have a great influence on the reaction,the electron-withdrawing group can significantly increase the reaction yield,and the electron-donating group can reduce the yield.This method provides a novel and practical way to synthesize aryltetrahydronaphthalene derivatives.