Synlett 2002(3): 0399-0402
DOI: 10.1055/s-2002-20450
LETTER
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Construction of the Azaspiro[5.5]undec-8-ene System Towards Gymnodimine Synthesis

Takashi Tsujimoto, Jun Ishihara, Mariko Horie, Akio Murai*
Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo, 060-0810, Japan
Fax: +81(11)7062714; e-Mail: amurai@sci.hokudai.ac.jp;
Further Information

Publication History

Received 29 December 2001
Publication Date:
05 February 2007 (online)

Abstract

In the course of the synthetic studies on gymnodimine, a potent shellfish toxin, the asymmetric construction of the azaspirocyclic part was achieved by the (-)-siam·Cu(SbF6)2 complex catalyzed intermolecular Diels-Alder reaction in high exo- and enantioselectivities.

7

i) NaH, THF, CBZ-Cl, 25 °C, 5 h (89%); ii) TMSOTf,
i-Pr2NEt, CH2Cl2, 25°C, 2 h; iii) Me2N+=CH2I-, CH2Cl2,
25 °C, 12 h; iv) MeI, THF, 25 °C, 2 h (68% for 3 steps).

8

The stereochemistry for the regioisomer of 8 has not been fully assigned yet.

9

9 was prepared from l-glutamic acid in a 5-step process:
(i) NaNO2, aq HCl, 25 °C, 20 h (77%); (ii) SOCl2, 80 °C,
12 h (98%); (iii) (E)-1-t-Butyldimethylsilyloxy-3-tributyl-stannylbut-2-ene, Pd(PPh3)4, ClCH2CH2Cl, 65 °C, 20 h (82%); (iv) Ph3P=CH2, THF, -10 °C, 2 min (96%).

18

21: A colorless oil; [α]D 24 -13.0 (c 0.24, CHCl3); 1H NMR (300 MHz, C6D6), δ 7.85-7.69 (m, 4 H), 7.52 (2 H, d, J = 7.3 Hz), 7.26-7.17 (8 H, m), 7.13 (1 H, t, J = 7.3 Hz), 5.78 (1 H, t, J = 5.5 Hz), 5.56 (1 H, d, J = 6.1 Hz), 5.28 (2 H, s), 4.84 (1 H, t, J = 6.6 Hz), 4.34 (2 H, d, J = 5.5 Hz), 3.79 (1 H, qui, J = 6.6 Hz), 3.65 (1 H, d, J = 8.0 Hz), 3.58-3.50 (1 H, m), 3.44-3.34 (1 H, m), 2.93 (1 H, brd, J = 17.1 Hz), 2.38 (1 H, brd, J = 17.1 Hz), 2.32 (1 H, dd, J = 11.5, 13.0 Hz), 2.18-2.05 (1 H, m), 1.86 (1 H, ddd, J = 2.7, 5.9, 13.2 Hz), 1.95-1.35 (12 H, m), 1.75, 1.74, 1.65, 1.60 (each 3 H, s), 1.11 (21 H, s), 1.08 (9 H, s), 0.80 (3 H, d, J = 6.6 Hz); IR(neat), 3071, 3048, 2951, 2930, 2891, 2863, 1782, 1771, 1714, 1612, 1471, 1461, 1428, 1389, 1297, 1252, 1180, 1111, 1060, 882, 837, 821, 777, 740, 701, 689, 658 cm-1; FAB-HR-MS, calcd. for C63H89NO8Si2 (M+) 1043.6127, found 1043.6149.