Scheme 1 Reagents and conditions: (i) 160 ЊC, 2 h; (ii) H3CNHOCH3ؒHCl (1.2 mol equiv.), Et3N (1.2 mol equiv.), bis(N-oxido-2-pyridyl) disulfide
(1.5 mol equiv.), Bu3P (1.5 mol equiv.), CH2Cl2, 18 ЊC, 16 h; (iii) (a) EtMgBr (3 mol equiv.), Et2O, 18 ЊC, 1 h then (b) 0.3 M aq. KHSO4 (excess),
Ϫ40 ЊC, 0.1 h then (c) NaHCO3 (excess), Ϫ40 ЊC to 18 ЊC; (iv) NaH (2 mol equiv.), (EtO)2POCH2CO2CH3 (2 mol equiv.), THF, 18 ЊC, 48 h; (v) AlCl3
(5 mol equiv.), Et2O, 18 ЊC, 5 h; (vi) POCl3 (1.1 mol equiv.), 1:33 v/v DMF–Et2O, 18 ЊC, 3 h; (vii) I2 (1.2 mol equiv.), AgOCOCF3 (1.2 mol equiv.),
CHCl3, 18 ЊC, 4 h; (viii) 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.5 mol equiv.), Pd(PPh3)4 (5 mol%), toluene, 2 M aq. Na2CO3
(excess), H3COH, 80 ЊC, 1.5 h; (ix) (a) KOH (excess), EtOH, 18 ЊC, 48 h then (b) 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium
chloride (excess), THF, 18 ЊC, 2 h.
2942, 1732, 706 cmϪ1 1H NMR (300 MHz, CD3COCD3)
;
δ 0.93 (3H, t, J = 7.5 Hz), 1.81–1.96 (3H, m), 2.40–3.20 (3H,
complex m), 2.67 (2H, d, J = 3.5 Hz), 3.66 (3H, s), 3.99 (2H,
m), 5.90 (1H, q, J = 1.65 Hz), 6.06 (1H, t, J = 3.25 Hz), 6.58
(1H, m); 13C NMR (75 MHz, CDCl3) δ 9.0, 20.1, 30.5, 33.0,
37.6, 44.7, 45.3, 51.3, 103.9, 107.3, 110.8, 118.7, 172.1; m/z 221
(43%, Mϩ ), 192 (70), 148 (100), 132 (82), 118 (17).
ؒ
Acknowledgements
We thank the Institute of Advanced Studies for financial
support including the provision of a post-doctoral fellowship
(to JS) and AMRAD (Melbourne) for
a post-doctoral
research award (to JS). Dr S. Marcuccio (CSIRO Molecular
Science, Clayton) and Dr H. Schuhbauer (SKW, Trostberg)
are thanked for supplying generous quantities of 2-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)aniline and 2-chloro-4,6-
dimethoxy-1,3,5-triazene, respectively.
Notes and references
‡ All new and stable compounds had spectroscopic data [IR, UV,
NMR, mass spectrum] consistent with the assigned structure. Satis-
factory combustion and/or high-resolution mass spectral analytical
data were obtained for new compounds and/or suitable derivatives.
1
§ Selected spectral data for 3: H NMR (300 MHz, CDCl3) 0.68 (3H,
Fig. 1 An ORTEP diagram (with 50% probability ellipsoids) of com-
pound 3 derived from X-ray crystallographic data.
t, J = 7.5 Hz), 1.44–1.68 (3H, m), 1.87 (1H, dt, J = 13.5 and 3.5 Hz),
1.94–2.03 (1H, m), 2.15 (1H, d, J = 11.5 Hz), 2.40 (1H, td, J = 13.5 and
3.6 Hz), 2.79 (1H, d, J = 12.4 Hz), 4.08 (1H, m), 4.83 (1H, dd, J = 14.3
and 6.0 Hz), 6.71 (1H, s), 7.10–7.16 (1H, m), 7.17 (1H, br s), 7.28–7.42
Experimental
(3H, m), 9.46 (1H, s); m/z 308 (56%, Mϩ ), 279 (75), 251 (42), 237 (100).
ؒ
¶ Crystal data for 3: C19H20N2O2, M = 308.38, T = 200(1) K, mono-
Methyl 2-(8-ethyl-5,6,7,8-tetrahydroindolizin-8-yl)acetate (10)
clinic, space group P21/n, Z = 4, a = 10.040(1), b = 12.331(1), c =
12.675(1) Å, β = 99.651(7)Њ, U = 1547.0(3) Å3, Dc = 1.324 g cmϪ3
,
Aluminium chloride (815 mg, 6.1 mmol) was added in small
portions to a chilled (ice-bath) and magnetically stirred solution
of the α,β-unsaturated ester 9 (270 mg, 1.22 mmol) in diethyl
ether (20 cm3). The reaction mixture was stirred at 18 ЊC for 5 h
then cooled and treated with water (15 cm3) followed by sulfuric
acid (20 cm3 of a 0.5 M aqueous solution). The separated
aqueous phase was extracted with diethyl ether (1 × 25 cm3)
and the combined organic phases were then dried (MgSO4),
filtered and concentrated under reduced pressure to give
F(000) = 656, µ(Mo-Kα) = 0.087 mmϪ1
,
3045 unique data
(2θmax = 27.5Њ), 1610 with I > 3σ(I), R = 0.048, Rw = 0.051, S = 1.15.
Images were measured on a Nonius Kappa CCD diffractometer
(Mo-Kα, graphite monochromator, λ = 0.71073 Å) and data extracted
using the DENZO package.20 Structure solution was by direct methods
(SIR92)21 and refinement was by full matrix least-squares on F
using the maXus program package.22 Atomic coordinates, bond lengths
and angles, and displacement parameters have been deposited at the
Cambridge Crystallographic Data Centre. CCDC reference number
lographic files in .cif format.
compound 10 (223 mg, 83%) as a light-yellow oil [Found:
ϩ
Mϩ , 221.1413. C13H19NO2 requires M , 221.1415]. νmax(neat)
ؒ
ؒ
1498
J. Chem. Soc., Perkin Trans. 1, 2000, 1497–1499