I. New Cycloadditions for the Synthesis of Nitrogen Heterocycles

Alkyliminoacetonitrile derivatives were investigated as dienophiles in the Diels-Alder reaction. These activated imines react with dienes in intramolecular [4+2] cycloadditions to provide products with either the quinolizidine or indolizidine ring system, depending on the length of the tether connecting diene and dienophile. Quinolizidine cycloadducts are formed in good yield and with high stereoselectivity whereas indolizidine cycloadducts are formed in only modest yields. A new oximinosulfonate dienophile derived from Meldrum's acid reacts in efficient and regioselective [4+2] cycloadditions with substituted dienes under Lewis acid promotion. The cycloadducts obtained from these reactions can be converted into substituted pyridine derivatives in high yields. This two-step pyridine annulation was successfully applied to the total synthesis of the pyridine alkaloids fusaric acid and S-(+)-fusarinolic acid. Some of the cycloadducts obtained in the reactions of this new dienophile are prone to undergo Stieglitz rearrangement, thereby producing pyrrolines. The rate and selectivity of the Diels-Alder reaction in supercritical carbon dioxide (scCO2) was investigated as a function of pressure and density. The rate of the reaction can be correlated to the density of the supercritical solution and increases from 2.8 to 4.0 x 10-5 L/mmol h upon increasing the density from 0.33 to 0.858 g/mL. The regioselectivity of several Diels-Alder reactions was found not to be significantly influenced by the solution density. The endo stereoselectivity of the Diels-Alder reaction between acrylonitrile and cyclopentadiene was found to increase by ca. 3% upon increasing the CO2 pressure from 103 to 300 bar or upon decreasing the pressure from 103 to 82 bar. The use of silica (SiO,) as a reaction promoter in scCO 2 leads to improvements in the yield and selectivity of Diels-Alder reactions. Thesis Supervisor: Rick L. Danheiser Title: Professor of Chemistry