Modified Fry Cyanation of a Chiral Pyridinium Salt: Asymmetric Syntheses of (–)-Coniine and (–)-Solenopsin A

The synthesis of chiral 2-cyano-Δ4-tetrahydropyridine 5 was carried out in 85 % yield through a modified two-step Fry reductive cyanation of pyridinium salt (+)-3c that used lithium triethylborohydride as the hydride donor. An alkylation–reduction sequence provided 2-alkyl-substituted tetrahydropyridines (+)-10a and (+)-10b in 72–75 % yield after chromatographic purification. This protocol has been applied to the asymmetric syntheses of piperidine alkaloids (–)-coniine and (–)-solenopsin A.