PREPARATION OF FUNCTIONALLY SUBSTITUTED 9-AZABICYCLO[4.2.1]NONA-2,4,7-TRIENES BY CATALYTIC CYCLOADDITION OF AZEPINES
The development of preparative methods for the targeted construction of functionally substituted 9-azabicyclo[4.2.1]nonadi(tri)enes, as well as the study of the possibility of their use in the creation of valuable drugs, is an important and popular task of modern organic synthesis. The 9-azabicyclo[4.2.1]nonane backbone is a key structural element of practically valuable alkaloids (anatoxin-a, pinnamine, bis-homoepibatidine, UB-165), which have a wide range of pharmacological properties. These alkaloids are of interest as potential drugs for the treatment of mental illnesses such as depression, schizophrenia, Parkinson’s and Alzheimer’s diseases associated with impaired production of neurotransmitters. According to the analysis of world literature, catalytic cycloaddition reactions involving N -substituted azepines or azacycloheptatrienes are an effective method for the preparation of 9-azabicyclo[4.2.1]nonadi(tri)enes. Previously, we proposed for the first time an efficient method for the synthesis of 9-azabicyclo[4.2.1]nonadi(tri)enes based on cobalt(I)-catalyzed [6π+2π] cycloaddition of alkynes, 1,3-diynes, and 1,2-dienes to N -carboethoxy-, phenoxy- and cholesteroxyazepines. To develop these studies, we carried out catalytic [6π+2π]-cycloaddition of terminal alkynes, including functionally substituted ones, to N -carboethoxy- and phenoxyazepines. It was found that the [6π+2π]-cycloaddition of terminal alkynes to N -carboethoxyazepine and N -carbophenoxyazepine under the action of the Co(acac)2(dppe)/Zn/ZnI2 catalytic system proceeds with the formation of new substituted 9-azabicyclo[4.2.1]nona-2,4,7-trienes in 89-95% yields as two N-(CO)OR1 rotamers. In all cases, the ratio of stereoisomers is 1:1 and does not depend on the nature of the starting azepine and alkyne. The resulting bridged azabicycles are of particular interest as key precursors in the synthesis of modern biologically active and medicinal compounds.