LETTER
A Short Synthesis of g-Lycorane using Ni/AcOH Mediated Radical Cyclisation
503
M.; Mori, M. J. Org. Chem. 1995, 60, 2016-2021. (c) Banwell,
tate (535 mg, 6.6 mmol) and nickel powder (3.82 g, 66 mmol);
the resulting mixture was stirred under reflux in an inert at-
mosphere for 10 h, then cooled to room temperature, diluted
with ether and filtered through Celite. Water was added to the
filtrate which was subsequently neutralised with saturated
aqueous sodium bicarbonate, washed with water, brine, dried
over magnesium sulfate, and concentrated in vacuo. The resi-
due was purified by silica gel column chromatography (hepta-
ne / ethyl acetate 9/1) to give 1-(6-bromo-3,4-dimethoxy-
benzyl)-1,4,5,6-tetrahydro-indol-2-one 9 (453 mg, 60%) as a
white solid (mp : 124-125°C, ether); 1H-NMR (200 MHz,
CDCl3) δ 1.83 (tt, J = 6.5, 5.9 Hz, 2H, CH2); 2.29 (td, J = 5.9,
4.8 Hz, 2H, CH2); 2.66 (td, J = 6,5, 1,6 Hz, 2H, CH2); 4.75 (s,
2H, NCH2); 5.55 (dt, J = 4.8, 1.6 Hz, 1H, C=CH); 5.84 (m, 1H,
CHCO); 5.94 (s, 2H, OCH2O); 6.51 (s, 1H, CH Ar); 6.99 (s,
1H, CH Ar); 13C-NMR (50 MHz, CDCl3) δ 23.5, 24.3, 24.4,
42.5, 101.8, 108.2, 111.4, 112.4, 112.5, 115.6, 129.8, 139.4,
147.5, 147.9, 148.0, 170.3. IR (cm-1) ν 1692, 1656, 1502,
1480; Anal. Calcd for C16H14NO3Br: C: 55.33; H: 4.07.
Found: C: 54.96; H: 3.82.
M. G.; Wu, A. W. J. Chem. Soc. Perkin Trans. 1 1994, 2671-
2672. (d) Grojahn, D. B.; Vollhardt, K. P. Synthesis 1993,
579-605. (e) Bäckvall, J.-E.; Anderson, G.; Stone, G. B.;
Gogoll, A. J. Org. Chem. 1991, 56, 2988-2993. (f) Pearson,
W. H.; Schkeryantz, J. M. J. Org. Chem. 1992, 57, 6783-6789.
(g) Sugiyama, N.; Narimiya, M.; Iida, H.; Kikuchi, T. J. Hete-
rocyl. Chem. 1988, 25, 1455-1457. (h) Magnus, P.; Hwang, G.
J. Chem. Soc. Chem. Commun. 1983, 693-694. (i) Iida, H.;
Aoyagi, S.; Kibayashi, G. J. Org. Chem. 1979, 44, 1074-1080.
(j) Umezawa, B.; Hoshino, O.; Sawaki, S.; Sato, S.; Numao,
N. J. Org. Chem. 1977, 42, 4272-4275. (k) Iida, H.; Aoyagi,
S.; Kibayashi, G. J. Chem. Soc. Perkin Trans. 1 1975, 2502-
2066. (l) Hara, H.; Hoshino, O.; Umezawa, B. Tetrahedron
Lett. 1972, 5031-5034. (m) Ganem, B. Tetrahedron Lett.
1971, 4105-4108. (n) Irie, H.; Nishitani, Y.; Sugita, M.; Uyeo,
S. J. Chem. Soc. Chem. Commun. 1970, 1313-1314. (o) Kote-
ra, K. Tetrahedron 1961, 12, 248-261.
(11) We have very recently devised another route to (±)-γ-lycorane
involving a cascade process starting with a nitrogen centered
radical: Hoang-Cong, X.; Quiclet-Sire, B.; Zard, S. Z.
Tetrahedron Lett, submitted.
(15) Data for 10 : 1H-NMR (200 MHz, CDCl3) δ 1.25-1.90 (m, 3H,
CH2); 2,03-2.16 (m, 2H, CH2); 2.48-2.59 (m, 1H, CH2); 2.95
(dm, J = 22.8 Hz, 1H, COCHH); 3.10 (dm, J = 22.8 Hz, 1H,
COCHH); 3.50 (m, 1H, CHAr); 4.22 (d, J = 15.6 Hz, 1H,
NCHH); 4.79 (d, J = 15.6 Hz, 1H, NCHH); 5.94 (s, 2H,
OCH2O); 6.64 (s, 1H, CH Ar); 6.79 (s, 1H, CH Ar). 13C-NMR
(50 MHz, CDCl3) δ 22.5, 22.9, 27.7, 33.0, 40.7, 41.8, 101.2,
105.6, 107.2, 108.0, 125.7, 130.1, 136.5, 146.1, 147.3, 175.4;
IR (cm-1) ν 2927, 1706, 1678, 1486.
(12) 1) Bromination of piperonal was performed in 61% yield ac-
cording to Khanapure, S. P.; Biehl, E. R. J. Org. Chem. 1990,
55, 1471-1475; 2) Oxime formation followed by zinc reduc-
tion in acetic acid at 70°C afforded amine 7 in 94% yield.
(13) Preparation of 8: A solution of cyclohexanone (0.52 ml, 5
mmol) and 6-bromopiperonylamine (1.15 g, 5 mmol) in tolue-
ne (5 ml) was heated under reflux in a Dean-Stark apparatus
for 3 hours. After evaporation of the solvant, the residue was
dissolved in dry toluene (25 ml) and cooled to 0°C. Triethyl-
amine (0.72 ml, 6 mmol) was added, followed by dropwise ad-
dition of trichloroacetyl chloride (0.61 ml, 5.5 mmol). The
solution was then stirred for 3 hours at room temperature. Wa-
ter was then added and the resulting mixture extracted with
ether, the organic layer was dried over magnesium sulfate and
concentrated in vacuo. The residue was cristallised from
ethanol to give N-(6-bromo-3,4-dimethoxybenzyl)-N-(cyclo-
hex-1-enyl)-2,2,2-trichloroacetamide 8 (1.66 g, 73%) as co-
lourless needles (mp : 138-139°C, ethanol); 1H-NMR (200
MHz, CDCl3) δ 1.56 (m, 2H, CH2); 1.69 (m, 2H, CH2); 2.02
(m, 2H, CH2); 2.25 (m, 2H, CH2); 4.55 (m, 1H, NCHH); 5.02
(m, 1H, NCHH); 5.65 (t, J = 3.6 Hz, 1H, C=CH); 5.98 (s, 2H,
OCH2O); 6.96 (s, 1H, CH Ar); 7.00 (s, 1H, CH Ar); IR (cm-1)
ν 1677; 1666; 1503; 1480. Anal. Calcd for C16H15NO3BrCl3:
C: 42.39; H: 3.34. Found: C: 42.39; H: 3.35.
(16) Data for 13 : 1H-NMR (200 MHz, CDCl3) δ 2.02 (q, J = 6.1
Hz, 2H, CH2); 2.57 (t, J = 6.1 Hz, 2H, CH2); 2.70 (td, J = 6.1,
1.5 Hz, 2H, CH2); 4.84 (s, 2H, NCH2); 5.82 (t, J = 1.5 Hz, 1H,
C=CH); 6.00 (s, 2H, OCH2O); 6.72 (s, 1H, CH Ar); 6.83 (s,
1H, CH Ar); IR (cm-1) ν 1667, 1508, 1489, 1466.
(17) Preparation of 11 : A solution of Bu3SnH (1.2 ml, 4.5 mmol)
and 1,1'-azobis(cyclohexanecarbonitrile) (220 mg, 0.9 mmol)
in toluene (10 ml) was slowly added (2 hours) to a refluxing
solution of 9 in toluene (20 ml). The resulting mixture was re-
fluxed for 15 h. The solvent was evaporated and the residue
immediately dissolved in acetic acid (10 ml). Sodium cyano-
borohydride (710 mg, 11.2 mmol) was added and the mixture
stirred for 24 h under argon. The solution was poured into wa-
ter, neutralised with saturated aqueous sodium bicarbonate
and extracted with ethyl acetate. The organic layer was dried,
concentrated, and the residue purified by silica gel column
chromatography (heptane / ethyl acetate 7/3) to give 11 (398
mg, 65%) whose spectroscopic data (1HNMR, 13CNMR, IR)
were identical to those reported in ref 10b.
(14) Synthesis of tetrahydroindolone 9: To a solution of N-alkenyl
trichloroacetamide 8 (990 mg, 2.2 mmol) in dry 2-propanol
(25 ml) were added acetic acid (2.5 ml, 44 mmol), sodium ace-
Synlett 1999, No. 4, 501–503 ISSN 0936-5214 © Thieme Stuttgart · New York