Synlett 2008(18): 2859-2863  
DOI: 10.1055/s-0028-1083543
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Expeditious Syntheses of (±)-allo-Sedamine and (±)-allo-Lobeline via a Combination of Aza-Sakurai-Hosomi and Hydroformylation Reactions

Thomas Spangenberg, Etienne Airiau, Mathieu Bui The Thuong, Morgan Donnard, Manuella Billet, André Mann*
Département de Pharmacochimie de la Communication Cellulaire, UMR 7175-LC-1 ULP/CNRS, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 Illkirch, France
e-Mail: andre.mann@pharma.u-strasbg.fr;
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Publikationsverlauf

Received 23 July 2008
Publikationsdatum:
15. Oktober 2008 (online)

Abstract

The expeditious preparation of allo-sedamine and allo-lobeline via 1,3-diastereoselective aza-Sakurai-Hosomi reaction followed by hydroformylation is reported.

6

Orientating experiments with different protecting groups on the alcohol were performed with TBS (5e/6e = 85:15), Bn (5e/6e = 75:25), Me (5e/6e = 70:30) using conditions from Table  [¹] , entry 1.

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Typical Procedure for an Aza-Sakurai-Hosomi Reaction: In a dry flask under argon were introduced 4 (0.756 mmol) and R²NH2 (0.756 mmol) in anhydrous CH2Cl2 (4 mL, 0.2 M). The mixture was cooled to 0 ˚C by means of an ice bath. Allylsilane (0.765 mmol) was then added followed by a dropwise addition of a 1 M solution of BF3˙OEt2 in CH2Cl2 (0.756 mmol). The reaction was stirred for 1 h at 0 ˚C before addition of sat. NaHCO3. The organic layer was extracted with CH2Cl2 (3 ×) and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography. Spectroscopic data for 6a: IR(film): 2952, 2928, 2856, 1696, 1508, 1250 cm. ¹H NMR (200 MHz, CDCl3): δ = 7.23-7.39 (m, 10 H), 5.70-5.80 (m, 1 H), 5.05-5.21 (m, 5 H), 4.82 (dd, J = 2.0, 9.1 Hz, 1 H), 3.80-3.91 (m, 1 H), 2.26-2.40 (m, 2 H), 1.93 (ddd, J = 2.9, 10.0, 13.8 Hz, 1 H), 1.68 (br d, J = 9.1 Hz, 1 H), 0.88 (s, 9 H), 0.05 (s, 3 H), -0.26 (s, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 155.9 (C), 145.0 (C), 136.9 (C), 134.5 (CH), 128.5 (CH), 128.3 (CH), 128.1 (CH), 128.0 (CH), 127.3 (CH), 125.9 (CH), 117.8 (CH2), 72.7 (CH), 66.5 (CH2), 48.4 (CH), 44.4 (CH2), 39.7 (CH2), 25.8 (Me), 18.1 (C), -4.5 (Me), -5.1 (Me). HRMS (ESI, positive, HCOOLi): m/z [M + Li] calcd for C23H39NO3Si: 446.2698; found: 446.2690.

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Typical Procedure for Hydroformylation: In a dry Schlenk glassware under argon were introduced Rh(CO)2acac (1 mol%) and anhydrous degassed THF (1 mL). Biphephos (2 mol%) was added and CO evolution was observed. Subsequent addition of homoallylic amide (and PPTS) was performed. The mixture was transferred via a syringe in a dry stainless autoclave under argon. The glassware was rinsed with anhydrous degassed THF (3 ×) to reach a final concentration of 0.04 M. The autoclave was purged (3 ×) with H2/CO (1:1) before setting the pressure at 5 bar. The autoclave was heated at 65 ˚C (internal temperature) by means of an oil bath. Once the reaction was finished, the autoclave was depressurized and the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography. Spectroscopic data for 7: IR(film): 2951, 2927, 2854, 1703, 1651, 1324, 1089, 1060, 833 cm. ¹H NMR (200 MHz, CDCl3): δ = 7.15-7.36 (m, 10 H), 6.79 (br d, J = 8.2 Hz, 0.5 H, rotamers), 6.66 (br d, J = 8.2 Hz, 0.5 H, rotamers), 5.16 (s, 2 H), 4.94 (m, 0.5 H, rotamers), 4.81 (m, 1 H), 4.65 (m, 0.5 H, rotamers), 4.45 (m, 0.5 H, rotamers), 4.14 (m, 0.5 H, rotamers), 1.72-2.13 (m,
6 H), 0.87, 0.85 (s, 9 H, rotamers), 0.1 (s, 1.5 H, rotamers), -0.03 (s, 1.5 H, rotamers), -0.24, -0.26 (s, 3 H, rotamers). ¹³C NMR (50 MHz, CDCl3): δ = 153.2, 152.9 (rotamers, C), 145.3, 144.6 (rotamers, C), 136.5, 136.4 (rotamers, C), 128.6 (CH), 128.5 (CH), 128.2 (CH), 128.0 (CH), 127.3 (CH), 126.2, 126.1 (rotamers, CH), 124.3, 123.7 (rotamers, CH), 106.2 (CH), 73.8 (CH), 67.4 (CH2), 49.1, 48.8 (rotamers, CH), 42.7 (CH2), 26.0 (Me), 25.5, 24.7 (rotamers, CH2), 18.2 (C), 17.8, 17.4 (rotamers, CH2), -4.5, -4.8 (rotamers, Me). HRMS (ESI, positive, HCOOLi): m/z [M + Li] calcd for C26H37NO3Si: 458.2698; found: 458.2685.