SYNTHESIS AND SYNTHETIC UTILITY OF 1-ACYL-5-(TRIALKYLSILYL)-1,2-DIHYDROPYRIDINES - SYNTHESIS OF (+/-)-ELAEOKANINE-A

The regioselective addition of Grignard reagents to the phenoxycarbonyl salts of 3-(trialkylsilyl)pyridines was studied. Most of the 3-(trialkylsilyl)pyridine salts gave a mixture of dihydropyridines on reaction with aliphatic Grignard reagents. However, all reactions using alkyl or aryl Grignard reagents and the 1-phenoxycarbonyl salt of 3-(triisopropylsilyl)pyridine, or 4-chloro-3-(triisopropylsilyl)pyridine, gave exclusively 1,2-dihydropyridines resulting from attack of the Grignard reagents at the C-6 position of the pyridinium salt. Vilsmeier-Haack formylation of 2-alkyl(aryl)-1-(phenoxycarbonyl)-5-(triisopropylsilyl)-1,2-dihydropyridines 8g,h and 10h occurs at C3. Friedel-Crafts acylation of 5-(trialkylsilyl)dihydropyridines 10 gave C-5 acylation via ipso substitution. In contrast, acylation of 10f,h,i with acyl triflates gives C-3 substitution. The triisopropylsilyl group of the C-3 acylated 1,2-dihydropyridines could be removed on reaction with HBr/HOAc in methylene chloride. The methodology developed for the regiospecific formation and acylation of 5-(triisopropylsilyl)-1,2-dihydropyridines was utilized in the total synthesis of the indolizidine alkaloid, (+)-elaeokanine A. The synthesis was achieved in a regiospecific manner from 3-(triisopropylsilyl)pyridine in six steps. © 1990, American Chemical Society. All rights reserved.