| The lanthanide mediated hydroamination reaction is a simple, yet powerful way of forming nitrogen heterocycles. The architecture of the catalyst and the ability to tune the metal-ligand system allows for the possibility of high stereoselectivity and yield. Previous efforts in our laboratory determined that the complex Cp*2NdCH(TMS)2 converted 2-substituted 8-nonen-4-amines to 2,6-disubstituted piperidines with greater than 100:1 selectivity for the formation of the cis isomer. A short synthesis of pinidinol, an alkaloid isolated from various pine and spruce species, was then carried out to exploit this stereoselective reaction.; Unlike other metal catalyzed hydroamination reactions, the lanthanides are able to affect a sequential hydroamination/C-C cyclization. In order to apply this method to the synthesis of natural products, the scope of the reaction was determined for the formation of substituted quinolizidines, indolizidines, pyrrolizidines. A methyl group was installed at diverse positions in the substrate to determine the substitution pattern that would provide the greatest diastereoselectivity. It was found that substrates containing a methyl group alpha or beta to the nitrogen provided the highest diastereoselectivity (>20:1) for the formation of quinolizidines and indolizidines. A novel procedure for substrate preparation is also presented.; Attempts were made to apply the sequential reaction toward the formation of quinolizines and indolizines using amino alkynes. Unfortunately, a complex mixture of products was obtained. Varying the catalyst, as well as the electronic characteristics of the alkyne, had little to no effect. It is believed that an intermolecular chelation of the alkyne to the metal center deactivated the catalytic species and enhanced the rate of impurity formation.; Finally, the sequential reaction was applied to the formation of tricyclic and tetracyclic aromatic nitrogen heterocycles. An array of ring sizes was explored to determine the diastereoselectivity. The electronic characteristics of the aromatic ring were also varied to determine how they affected the cascade reaction. It was found that the benzo[a]quinolizine and the pyrido[2,1,a]isoindolizine ring systems formed with the highest diastereoselectivity (>20:1), regardless of the electronic characteristics of the aromatic ring. |
