ASYMMETRIC-SYNTHESIS OF 2-ALKYL(ARYL)-2,3-DIHYDRO-4-PYRIDONES BY ADDITION OF GRIGNARD-REAGENTS TO CHIRAL 1-ACYL-4-METHOXYPYRIDINIUM SALTS

The asymmetric synthesis of 2-alkyl(aryl)-2,3-dihydro-4-pyridones 3 by addition of various Grignard reagents to chiral 1-acyl-4-methoxypyrid inium salts was studied in detail. Chiral pyridinium salts formed from 4-methoxy-3-(triisopropylsilyl)pyridine (2f), and (-)-8-arylmenthyl c hloroformates, or (-)-trans-2-(alpha-cumyl)cyclohexyl chloroformate, g ave the best results, with diastereomeric selectivities ranging from 6 0 to 94%. When 4-methoxy-3-(trialkylstannyl)pyridines were used, desta nnylated 2-alkyl-2,3-dihydropyridones 3a resulted in good yield. The s ize of the C-3 substituent, the auxiliary, the solvent, the reaction t emperature, and the structure of the Grignard reagent were varied to d etermine their effect on the yield and the degree of asymmetric induct ion. The chiral auxiliary and the C-3 triisopropylsilyl group can be r emoved from 3f, and the auxiliary recovered, on treatment with sodium methoxide in methanol followed by aqueous acid. The resulting 2,3-dihy dropyridones 8 are useful chiral building blocks for the enantioselect ive synthesis of various alkaloids.