Derivatization of 2,3-dihydro-4-pyridones via the Nozaki-Hiyama-Kishi reaction. Studies towards the asymmetric synthesis of (-)-Morphine. Asymmetric synthesis of dihydroisoindolones.

by Hiebel, Anne-Cecile

ABSTRACT HIEBEL, ANNE-CECILE: Derivatization of 2,3-dihydro-4-pyridones via the Nozaki-Hiyama-Kishi reaction. Studies towards the asymmetric synthesis of (-)-morphine. Asymmetric synthesis of dihydroisoindolones. (under the direction of Dr. Daniel L. COMINS) The highly versatile N-acyl-2,3-dihydropyridone system, developed in Dr. Comins? group, was investigated as a precursor to the Nozaki-Hiyama-Kishi reaction. Under modified conditions, various aldehydes reacted successfully with the organochromium(III) species generated by treatment of 5-iodo-2,3-dihydro-4-pyridones and a mixture of CrCl2/NiCl2. The ?-hydroxy enecarbamates obtained were evaluated as N-acyliminium ion precursors and treated under various Lewis acid/nucleophile combinations. A wide variety of 1,4 substitution products were isolated. Another study, featuring the N-acyl-2,3-dihydropyridone system, aimed at the asymmetric synthesis of (-)-morphine via N-acylpyridinium salt chemistry. Finally, the use of the chiral TCC auxiliary was extended to dihydroisoindolones. A quaternary center was successfully installed, and the products were derivatized into potential chiral building blocks.