The synthesis of (1S,8aS)-1-hydroxyindolizidine using a stereoselective Grignard addition to an N-benzyl-3-deoxy sugar imine derived from D-Glucose

A highly stereoselective approach to 1-hydroxyindolizidine is described using a Grignard reaction on N-benzyl imine derived from 3-deoxy-1,2-O-isopropylidine-α-d-xylo-pentodialdofuranose and reductive cyclization as key steps.

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(S)-N-Benzyl-1-((3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)pent-4-en-1-amineC19H27NO3[α]D28=-9.6 (c 1.51, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (3aR,5R,6aR)

Benzyl((S)-1-((3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)pent-4-enyl)carbamateC27H33NO5[α]D28=-23.3 (c 0.9, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (3aR,5S,6aR)

Benzyl((S)-1-((3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-5-hydroxypentyl)carbamateC27H35NO6[α]D30=-27.7 (c 1.55, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (3aR,5S,6aR)

Benzyl(S)-1-((3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-5-hydroxypentylcarbamateC20H29NO6[α]D30=-40.2 (c 0.55, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (S,3aR,5S,6aR)

(S)-Benzyl 2-((3aR,5S,6aR)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)piperidine-1-carboxylateC20H27NO5[α]D30=-60.7 (c 2.57, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (3aR,5S,6aR)

(S)-Benzyl 2-((2S,4R)-4,5-dihydroxytetrahydrofuran-2-yl)piperidine-1-carboxylateC17H23NO5[α]D30=-47.6 (c 1.48, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (2S,4R)

(S,E)-Benzyl 2-(3-oxoprop-1-enyl)piperidine-1-carboxylateC16H19NO3[α]D30=-21.5 (c 0.58, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (S)

(S)-Benzyl 2-((1S,3R)-1,3,4-trihydroxybutyl)piperidine-1-carboxylateC17H25NO5[α]D30=-43.3 (c 0.4, CHCl3)Source of chirality: d-glucoseAbsolute configuration: (S,1S,3R)

(1S,8aS)-1-HydroxyindolizidineC8H15NO[α]D30=+23.5 (c 0.8, EtOH);Source of chirality: d-glucoseAbsolute configuration: (1S,8aS)