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Synthesis 2002(7): 0951-0957
DOI: 10.1055/s-2002-28505
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Allyltitanation. Synthesis of (-)-Slaframine

Janine Cossy*a, Catherine Willisa, Véronique Bellostaa, Laurent Saint-Jalmesb
a Laboratoire de Chimie Organique associé au CNRS, ESPCI, 10 rue Vauquelin, 75231 Paris Cedex 05, France
Fax: +33(1)40794660; e-Mail: janine.cossy@espci.fr;
b Rhodia RECHERCHES, Centre de Recherches de Lyon, 85 rue des frères Perret, 69192 Saint-Fons, France
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Publication History

Received 2 April 2002
Publication Date:
14 May 2002 (online)

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Abstract

An enantioselective synthesis of the indolizidine alkaloid (-)-slaframine from aldehyde 1 is reported. The stereogenic centers at C-1 and C-8a are introduced by an enantioselective allyltitanation and a Mitsunobu reaction. Reductive double cyclization of the acyclic compound (-)-10 affords the bicyclic skeleton of (-)-slaframine.

Key words

allyl complexes - titanium - Mitsunobu reaction - indolizidine - slaframine

19

The direct hydroboration of alcohol (+)-2 without silylation of the homoallylic alcohol function (BH3·THF then H2O2, NaOH) led to the formation of 5 and 5′ with an overall yield of 50% and a 60/40 ratio of 5/5′. See ref. [18]

20

Compound (+)-11′ was synthesized according to a strategy similar to the one used for obtaining (+)-11 However the deprotection of the PMP group by using CAN produced the decomposition of 11′.

Scheme 4

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(-)-Slaframine was transformed into the more stable N-acetylslaframine (Ac2O pyridine): [α]D 20 -13.3 (c 0.8, EtOH) {lit. [16c] [α]D 20 -11.2 (c 1.45, EtOH)}; mp 138-140 °C (lit. [16c] mp 139-141 °C); IR (CHCl3): 3300, 1730, 1650, 1545, 1440 cm-1; 1H NMR (CDCl3, 300 MHz) δ = 6.62 (br m, 1 H), 5.25 (ddd, 1 H, J = 7.4, 4.8, 2.2 Hz), 4.21 (dt, 1 H J = 8.5, 2.9 Hz), 3.14-3.02 (m, 2 H), 2.29 (m, 1 H), 2.19 (dd, 1 H, J = 11.4, 2.6 Hz), 2.08 (s, 3 H), 2.00 (s, 3 H), 2.07-1.87 (m, 2 H), 1.81 (m, 1 H), 1.65-1.56 (m, 2 H), 1.48 (m, 1 H); 13C NMR (CDCl3, 75 MHz) δ = 170.5 (s), 169.3 (s), 74.4 (d), 67.4 (d), 57.4 (t), 52.9 (t), 43.6 (d), 30.3 (t), 28.0 (t), 23.2 (q), 21.0 (q), 20.3 (t). The physical and spectral data are identical to those reported. [16c] [n]