SYNTHESIS OF CHIRAL HYDROXYLATED QUINOLIZIDINES VIA VINYLOGOUS BISCHLER-NAPIERALSKI NITRILIUM ION CYCLIZATIONS

Treatment of the amido esters 9 and 17 with PPSE (polyphosphoric acid trimethylsilyl ester) followed by NaBH4 in ethanol gave the quinolizid inones 11-14 and 19 via a vinylogous Bischler-Napieralski nitrilium io n cyclization-reductive lactamization two-step process. Subsequent ozo nolysis and reduction afforded chiral hydroxylated quinolizidines in m oderate to good yield. In contrast to five-membered-ring formation, si x-membered-ring formation via nitrilium-ion cyclization requires a p-m ethoxy-substituted styryl terminator. The effect para-substituted styr yl terminators have on the energy of activation and Delta H for the cy clization process has been calculated by semiempirical and ab initio m ethods.