Part I. Study of 1-acyl-2-dimethylphenylsilyl-2,3-dihydro-4-pyridone as synthetic intermediates ; Part II. Synthesis of enantiopure nicotine derivatives from nicotine

by Smith, Emilie Despagnet.

SMITH, EMILIE DESPAGNET: Part I. Study of 1-Acyl-2-dimethylphenylsilyl-2,3-dihydro- 4-pyridone as Synthetic Intermediates. Part II. Synthesis of Enantiopure Nicotine Derivatives from Nicotine. (Under the direction of Dr. Daniel L. Comins.) Various methodologies were investigated to build synthetic intermediates from 1-acyl-2dimethylphenylsilyl-2,3-dihydro-4-pyridones and to synthesize nicotine derivatives from nicotine. In the first part of this document, the synthesis and reactivity of 1-acyl-2dimethylphenylsilyl-2,3-dihydro-4-pyridone were investigated. This dihydropyridone was synthesized from the addition of dimethylphenylsilyl Grignard to the 1-acyl-4methoxypyridinium salt with a 90% yield and 98% de. A variety of reactions including 1,4additions and the synthesis of the corresponding dihydropyridine was accomplished. In the second part, various methodologies were discovered to synthesize enantiopure nicotine derivatives from nicotine. Regioselective substitution reactions for functionalization at C-4, C-5 and C-6 of the pyridine ring were achieved. The synthesis of novel C-4 substituted and unsubstituted dihydronicotines was also developed. The von Braun reaction was applied to give enantiopure pyrrolidine ring-opened products.