The formal synthesis of isofebrifugine using stereoselective intramolecular Michael addition

The formal synthesis of isofebrifugine, a bioactive alkaloid, was achieved via a stereoselective intramolecular Michael addition reaction from d-mannitol.

Figure optionsDownload as PowerPoint slide

(S,E/Z)-Methyl 3-(2,2-dimethyl-1,3-dioxolan-4-yl)acrylateC10H16O4[α]D25=+4.3 (c 1.8, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (3S)

(S)-3-(2,2-Dimethyl-1,3-dioxolan-4-yl)propan-1-olC8H16O3[α]D25=+7.4 (c 1.3, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (3S)

(S)-4-(3-Azidopropyl)-2,2-dimethyl-1,3-dioxolaneC8H15N3O2[α]D25=+6.5 (c 1.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(S)-5-Azidopentane-1,2-diolC5H11N3O2[α]D25=-7.4 (c 1.2, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(S)-5-Azido-1-(tert-butyldimethylsilyloxy)pentan-2-olC11H25N3O2Si[α]D25=+1.1 (c 1.0, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(S)-(5-Azido-2-(benzyloxy)pentyloxy)(tert-butyl)dimethylsilaneC18H31N3O2Si[α]D25=-21.6 (c 2.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(S)-5-Azido-2-(benzyloxy)pentan-1-olC12H17N3O2[α]D25=-5.0 (c .9, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(S)-tert-Butyl 4-(benzyloxy)-5-hydroxypentylcarbamateC17H27NO4[α]D25=-13.2 (c .8, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(S,E)-tert-Butyl 4-(benzyloxy)-7-oxooct-5-enylcarbamateC20H29NO4[α]D25=-15.2 (c 1.2, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4S)

(2S,3S)-tert-Butyl 3-(benzyloxy)-2-(2-oxopropyl)piperidine-1-carboxylateC20H29NO4[α]D25=+22.0 (c 1.7, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S,3S)

(2R,3S)-tert-Butyl 3-(benzyloxy)-2-(2-oxopropyl)piperidine-1-carboxylateC20H29NO4[α]D25=-42.3 (c 1.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3S)

(2S,3S)-tert-Butyl 3-(benzyloxy)-2-(3-bromo-2-oxopropyl)piperidine-1-carboxylateC20H28NO4Br[α]D25=−19.3 (c 0.7, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S,3S)

(2R,3S)-tert-Butyl 3-(benzyloxy)-2-(3-bromo-2-oxopropyl)piperidine-1-carboxylateC20H28NO4Br[α]D25=-32.2 (c 0.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3S)