| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1345410 | Tetrahedron: Asymmetry | 2013 | 4 Pages |
Homocalycotomine enantiomers (R)-4 and (S)-4 were prepared by the Candida antarctica lipase B (CAL-B)-catalysed asymmetric O-acylation of N-Boc-protected 2-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)ethanol (±)-1. The preliminary small-scale experiments were performed either in a continuous-flow system or as batch reactions, while the preparative-scale resolution was carried out in two steps with vinyl acetate as the acyl donor in the presence of Et3N and Na2SO4 in toluene at 3 °C, as a batch reaction. Treatment of the resulting amino alcohol (S)-1 and amino ester (R)-3 (ee ⩾94%) with 18% HCl, and then with 5 M NaOH, furnished the desired (R)-4 and (S)-4 without a decrease in the enantiomeric excess (ee ⩾94%).
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(1S)-N-(tert-Butoxycarbonyl)-1-(2-hydroxyethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolineC18H27NO5ee = 94% by HPLC on a Chiralpak IA column[α]D25=+95 (c 0.24, CHCl3)Source of chirality: CAL-B-catalysed enantioselective acylationAbsolute configuration: (1S)
(1R)-N-(tert-Butoxycarbonyl)-1-(2-acetoxyethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolineC20H29NO6ee = 95% by HPLC on a Chiralpak IA column[α]D25=-49 (c 0.2, CHCl3)Source of chirality: CAL-B-catalysed enantioselective acylationAbsolute configuration: (1R)
(1S)-1-(2-Hydroxyethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolineC13H19NO3ee = 94% by HPLC on a Chiralpak IA column[α]D25=+9 (c 0.2, CHCl3)Source of chirality: CAL-B-catalysed enantioselective acylationAbsolute configuration: (1S)
