Stereoselective total synthesis of the piperidine alkaloids, (+)-coniine, (+)-pseudoconhydrine, and (+)-sedamine through a common intermediate

The stereoselective total synthesis of the piperidine alkaloids, (+)-coniine, (+)-pseudoconhydrine and (+)-sedamine has been achieved through a common intermediate generated from butane-1,4-diol. The synthetic sequence involves a Maruoka asymmetric allylation and ring-closing metathesis as the key steps.

Figure optionsDownload as PowerPoint slide

(R)-7-(tert-Butyldimethylsilyloxy)hept-1-en-4-olC13H28O2Si[α]D25=-5.4 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R)

(S)-N-Allyl-7-(tert-butyldimethylsilyloxy) hept-1-en-4-amineC16H33NOSi[α]D25=+11.6 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S)

(S)-tert-Butyl 6-(3-hydroxypropyl)-5,6-dihydro pyridine-1(2H)-carboxylateC13H23NO3[α]D25=+32.5 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (6S)

(S)-tert-Butyl 6-propyl-5,6-dihydro pyridine-1(2H)-carboxylateC13H23NO2[α]D25=+15.7 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (6S)

(2S,5S)-tert-Butyl 5-hydroxy-2-propyl piperidine-1-carboxylateC13H25NO3[α]D25=+9.3 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S, 5S)

(R)-tert-Butyl 2-allylpiperidine-1-carboxylateC13H23O2[α]D25=+19.3 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(R)-tert-Butyl 2-((R)-2-hydroxy-2-phenylethyl) piperidine-1-carboxylateC18H27NO3[α]D25=+63.6 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R, 2’R)