Asymmetric synthesis of 2-alkyl(aryl)-2,3-dihydro-4-pyridones by addition of Grignard reagents to chiral 1-acyl-4-methoxypyridinium salts

Article abstract of DOI:10.1021/ja00090a019

The asymmetric synthesis of 2-alkyl(aryl)-2,3-dihydro-4-pyridones 3 by addition of various Grignard reagents to chiral 1-acyl-4-methoxypyridinium salts was studied in detail. Chiral pyridinium salts formed from 4-methoxy-3-(triisopropylsilyl)pyridine (2f), and (-)-8-arylmenthyl chloroformates, or (-)-trans-2-(α-cumyl)cyclohexyl chloroformate, gave the best results, with diastereomeric selectivities ranging from 60 to 94%. When 4-methoxy-3-(trialkylstannyl)pyridines were used, destannylated 2-alkyl-2,3-dihydropyridones 3a resulted in good yield. The size of the C-3 substituent, the auxiliary, the solvent, the reaction temperature, and the structure of the Grignard reagent were varied to determine their effect on the yield and the degree of asymmetric induction. The chiral auxiliary and the C-3 triisopropylsilyl group can be removed from 3f, and the auxiliary recovered, on treatment with sodium methoxide in methanol followed by aqueous acid. The resulting 2,3-dihydropyridones 8 are useful chiral building blocks for the enantioselective synthesis of various alkaloids.