A 4-spirocyclic Tetrahydroisoquinoline Skeleton Was Constructed In Series By Aziridine Ring Opening And Pictet-Spengler Reaction

Spiroannulated tetrahydroisoquinolines,as a kind of heterocyclic compounds containing the nitrogen atom,were widely found in a lot of natural products and drug-related molecules with various biological activities.It was not surprising that spiroannulated tetrahydroisoquinoline skeletons have been considered as “privileged structures”for bioactive evaluation in drug discovery.However,there are only a few reports about spiroannulated tetrahydroisoquinolines in the known literature due to the giant challenge for the construction of them.Therefore,developing general and effective methodologies for the synthesis of 4-spiroannulated tetrahydroisoquinoline is still highly desirable.In this paper,we mainly introduce the efficient construction of4-spiroannulated tetrahydroisoquinolines by a tandem reaction.The Pictet-Spengler reaction of ?-arylamines and aldehydes is one of the most powerful methods for the construction of various tetrahydroisoquinolines.In this paper,we designed and synthesized a new type of 2,2-disubstituted aziridines with OTBS groups and aryl groups at two different substitutions of aziridine ring.We envisaged that this kind of substrates underwent sequential ring opening of aziridines and Pictet-Spengler reaction to provide a series of 4-spiroannulated tetrahydroisoquinolines.The advantages of the tandem reaction designed by us include high bonding efficiency and cyclization efficiency,broad substrate scope,mild conditionsand good generality of the ring size in product.It provided a good choice for constructing the molecular library of 4-spiroannulated tetrahydroisoquinolines.