Synthesis of (+)-coniceine via reductive photocyclization of dienamides: an entry to indolizidines

This paper describes the establishment of a new synthetic route to the hydrobromide salt of (+)-coniceine 1 with high enantiopurity in five steps and 8% overall yield. The key step is the reductive photocyclization of an acyclic chiral dienamide, for which a convenient one-pot synthesis is described.

Figure optionsDownload as PowerPoint slide

N-(4-(Benzyloxy-1-methylene-butyl)-N-(1-(S)-phenyl-ethyl)-acrylamideC23H27NO2[α]D22=-82.8 (c 1.50, MeOH)Source of chirality: chiral starting materialAbsolute configuration: (S)

(S)-2-(3-Benzyloxy-propyl)-1-(1′-(S)-phenyl-ethyl)-piperidineC23H31NOEe >97% (vide infra)[α]D22=-68.4 (c 1.00, MeOH)Source of chirality: asymmetric synthesis (reductive photocyclization of chiral dienamide)Absolute configuration: (1S,2S)

(+)-Coniceine hydrobromideC8H16BrNEe >97% (determined by NMR-experiments)[α]D22=+5.5 (c 0.88, EtOH)Source of chirality: asymmetric synthesis (reductive photocyclization of chiral dienamide)