| This thesis presents the preparation of 2-substituted 1,2-dihydropyridines and the utilization of those intermediates in the synthesis of enantio-enriched 2-substituted and polysubstituted tetrahydropyridines and piperidines.; In the first chapter, we expose precedents of 2-substituted 1,2-dihydropyridines and tetrahydropyridines synthesis. We then introduce the work of our research group in this field.; In the second chapter, we describe our work in the optimization of the regioselectivity of nucleophilic addition to a chiral pyridinium salt. This allows the regio- and diastereoselective preparation of 2-substituted 1,2-dihydropyridines. We then describe precedents of L-Pipecolic acid syntheses, followed by our work in the synthesis of this amino acid from diastereoenriched 2-phenyl-1,2-dihydropyridine. The phenyl substituent at the 2-position acts as a masked carboxylic acid group.; In the third chapter, we show that nucleophilic addition to 3-substituted pyridinium salts leads preferentially to 2,3-disubstituted 1,2-dihydropyridines. Those are oxidized to 2,3-disubstituted pyridines with manganese triacetate and periodic acid. Nucleophilic addition to a chiral 3-substituted N-iminopyridinium salt allows for the efficient and stereoselective synthesis of L-733,061, a cis-2,3-disubstituted piperidine.; In the fourth chapter, we describe the synthesis of trans-2,3-disubstituted 1,2,3,6-tetrahydropyridines from 2-substituted 1,2-dihydropyridines. This is accomplished by a tandem hetero-Diels-Alder reaction with nitrosobenzene or singlet oxygen, followed by alane reduction. The tetrahydropyridinol produced after the reaction of a 1,2-dihydropyridine with singlet oxygen leads to the efficient stereoselective synthesis of (2S,3S)-trans-3-hydroxypipecolic acid.; Finally, the asymmetric synthesis of 2,6-disubstituted 3-piperidinols with a 2,3-cis-2,6-trans relative stereochemistry is described in the last chapter. This pattern is prepared by mono-hydrogenation of 2-substituted 1,2-dihydropyridines and a highly stereoselective tandem epoxidation-nucleophilic addition reaction with a protic or organometallic nucleophile. This methodology leads to an efficient and stereoselective synthesis of (-+-) julifloridine.; Keywords. - Dihydropyridine, - Chiral pyridinium salt, - Piperidine, - L-Pipecolic acid, - L-733,061, - Tetrahydropyridine, - Tetrahydropyridinol, - (2S,3S)-trans-3-Hydroxypipecolic acid; - Piperidinol; - (+)-Julifloridine. |
