The Catalytic Asymmetric Construction Of Pyrrolo[1,2-a] Indole Skeleton And Research On The Synthesis Of Ibuprofen

The chiral pyrrolo[1,2-a]indole skeleton exists in many natural products and drug molecules,so the asymmetric construction of such skeletons is particularly important.In recent years,the synergistic catalysis of metal and organic small molecules has gradually become a hot spot in the field of organic synthesis.The first part of this paper mainly focuses on the asymmetric[3+2]cycloaddition reaction of 2-indole allyl carbonate and formylcyclopropanes catalyzed by metal iridium and N-heterocyclic carbenes to construct the pyrrolo[1,2-a]indoles with two continuous chiral centers in good yield and excellent stereoselectivity.It provides new strategies and new ideas for the efficient asymmetric construction of such frameworks.Ibuprofen is a non-steroidal anti-inflammatory drug with antipyretic and analgesic effects.It has the characteristics of good curative effect and small side effects,and has been widely used all over the world.The second part of this article summarized the existing synthetic routes of ibuprofen firstly,and then designed a new synthetic route.In this route 1-bromo-4-isobutylbenzene and diethyl malonate was used as starting materials to obtain the key intermediate through copper-catalyzed coupling reaction.The intermediate is methylated and decarboxylated and hydrolyzed to obtain the final product ibuprofen.The total yield of the reaction is 36%.Conditional screening and optimization of key steps of the new route laid the foundation for subsequent pilot scale-up.