<p>Five-membered rings are readily prepared by <i>5-exo-trig</i> radical cyclization. This thesis is concerned with novel methodology for pyrrolidine synthesis. We have synthesised selenium containing radical precursors from aziridines and α-phenylseleno ketones, and cyclized them to 2,4- and 3,4-disubstituted pyrrolidines. A few examples of <i>5-exo-dig</i> cyclization were also demonstrated. In another study we investigated the capacity of the nitrogen protecting group to direct diastereoselectivity in the formation of 2,4-disubstituted pyrrolidines. The diphenylphosphinoyl protecting group directed cyclization to occur in a highly <i>cis</i>-selective manner. When cyclizations were performed at 17 ^oC, <i>cis</i>/<i>trans</i>-ratios as high as 24/1 were obtained. In contrast, cyclization of the unprotected pyrrolidine precursor afforded the <i>trans</i>-diastereomer as the major product (<i>cis</i>/<i>trans </i>= 1/3.3 – 1/20). We also examined the use of a hydroxyl auxiliary for controlling diastereoselectivity in radical cyclization. The required selenium containing radical precursors were synthesised from 2-cyanoaziridines by addition of organometallic reagents, reduction of the resulting aziridine ketone, and benzeneselenol ring-opening of the aziridine. Cyclization at 17 ^oC produced 2,4-disubstituted pyrrolidines substantially enriched in the <i>trans</i>-isomer (<i>cis</i>/<i>trans</i> = 1/9 – 1/12). Novel radical cyclization approaches to thiazolines and pyrrolines were also tried.</p><p>The thesis also describes attempts to improve the Hassner aziridine synthesis by employing stannous chloride as a functional group tolerant reducing agent.</p>

Five-membered rings are readily prepared by 5-exo-trig radical cyclization. This thesis is concerned with novel methodology for pyrrolidine synthesis. We have synthesised selenium containing radical precursors from aziridines and α-phenylseleno ketones, and cyclized them to 2,4- and 3,4-disubstituted pyrrolidines. A few examples of 5-exo-dig cyclization were also demonstrated. In another study we investigated the capacity of the nitrogen protecting group to direct diastereoselectivity in the formation of 2,4-disubstituted pyrrolidines. The diphenylphosphinoyl protecting group directed cyclization to occur in a highly cis-selective manner. When cyclizations were performed at 17 oC, cis/trans-ratios as high as 24/1 were obtained. In contrast, cyclization of the unprotected pyrrolidine precursor afforded the trans-diastereomer as the major product (cis/trans = 1/3.3 – 1/20). We also examined the use of a hydroxyl auxiliary for controlling diastereoselectivity in radical cyclization. The required selenium containing radical precursors were synthesised from 2-cyanoaziridines by addition of organometallic reagents, reduction of the resulting aziridine ketone, and benzeneselenol ring-opening of the aziridine. Cyclization at 17 oC produced 2,4-disubstituted pyrrolidines substantially enriched in the trans-isomer (cis/trans = 1/9 – 1/12). Novel radical cyclization approaches to thiazolines and pyrrolines were also tried. The thesis also describes attempts to improve the Hassner aziridine synthesis by employing stannous chloride as a functional group tolerant reducing agent.