Synthesis of the 3,4,5-Trimethoxy-2-(3,4-methylenedioxy-6-nitrophenyl)
Letters in Organic Chemistry, 2012, Vol. 9, No. 8 571
H), 7.80 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3) ꢀ = 11.3, 13.7,
27.3, 29.0, 102.7, 105.4, 114.6, 137.0, 148.7, 152.7 ppm. Anal.
Calcd for C19H31NO4Sn: C, 50.03; H, 6.85; N, 3.07. Found: C,
50.40; H, 7.17; N, 2.83.
Dallacker, F.; Wagner, A. Derivatives of 1,3-benzodioxole, 52.
Preparation and reactions of 1,3-dioxolo[4,5-b]phenazines. Z. Na-
turforsch., 1984, 39b, 936-949.
Molander, G.A.; George, K.M.; Monovich, L.G. Total synthesis of
(+)-isoschizandrin utilizing a samarium(II) iodide promoted 8-endo
ketyl-olefin cyclization. J. Org. Chem., 2003, 68, 9533-9540.
Mee, S.P.H.; Lee, V.; Baldwin, J.E. Stille coupling made easier-the
synergic effect of copper(I) salts and the fluoride ion. Angew.
Chem. Int. Ed., 2004, 43, 1132-1136.
Littke, A.F.; Schwarz, L.; Fu, G.C. Pd/P(t-Bu)3: A mild and general
catalyst for stille reactions of aryl chlorides and aryl bromides. J.
Am. Chem. Soc., 2002, 124, 6343-6348.
temperature for 15 min and then water (20 mL) was added. MeOH
was removed under reduced pressure and the aqueous phase was
extracted with CH2Cl2. The organic phase was separated, dried
over Na2SO4 and evaporated under reduced pressure. The crude
product was purified by silica gel column chromatography using a
CH2Cl2/AcOEt mixture (8:2) as eluent to afford slightly unstable
alcohol 18 as a yellow oil (478 mg, 95%) which was used directly
in the next step. 1H NMR (300 MHz, CDCl3) ꢀ = 1.90 (s, 1 H), 3.65
(s, 3 H), 3.85 (s, 3 H), 3.90 (s, 3 H), 4.30 (d, J = 12 Hz, 1 H), 4.35
(d, J = 12 Hz, 1 H), 6.15 (s, 2 H), 6.65 (s, 1 H), 6.85 (s, 1 H), 7.55
(s, 1 H) ppm. 13C NMR (75 MHz, CDCl3) ꢀ = 56.0, 60.9, 62.9,
103.2, 105.3, 107.1, 111.4, 123.6, 127.6, 133.7, 141.1, 143.3,
147.4, 150.2, 151.3, 153.4 ppm; A 1 M solution of PBr3 in CH2Cl2
(1.32 mL, 1.32 mmol) was added dropwise to a stirred solution of
freshly purified alcohol 18 (478 mg, 1.32 mmol) in anhydrous
CH2Cl2 (35 mL) at 0 °C. The mixture was stirred at 0 °C for 30
min, then at room temperature for 15 min. The mixture was poured
onto ice and the organic phase was washed with saturated aq. Na-
HCO3 solution, dried over Na2SO4, and evaporated under reduced
pressure. The crude product was purified by silica gel column
chromatography using CH2Cl2 as eluent to afford 19 as a yellowish
[9]
[10]
[11]
[12]
[13]
Preparation of 2-tributylstannyl-3,4,5-trimethoxybenzaldehyde
(15): To a stirred solution of benzaldehyde 14 (858 mg, 3.12
mmol) and Bu6Sn2 (2.4 mL, 4.70 mmol) in anhydrous toluene (10
mL) under N2, was added Pd(PPh3)4 (185 mg, 0.16 mmol). The re-
sulting mixture was then refluxed for 48 h and the solvent was re-
moved under reduced pressure. The crude product was purified by
silica gel column chromatography using a CH2Cl2/cyclohexane
mixture (9:1) as eluent to afford 15 as a clear oil (1.21 g, 80%). 1H
NMR (300 MHz, CDCl3) ꢀ = 0.85 (t, J = 7 Hz, 9 H), 1.05-1.50 (m,
18 H), 3.85 (s, 3 H), 3.90 (s, 6 H), 7.25 (s, 1 H), 9.80 (s, 1 H) ppm.
13C NMR (75 MHz, CDCl3) ꢀ = 12.6, 13.8, 27.4, 29.3, 56.2, 60.7,
60.9, 110.2, 133.5, 137.9, 147.0, 154.3, 159.0, 192.7 ppm. Anal.
Calcd for C22H38O4Sn: C, 54.45; H, 7.89. Found: C, 54.81; H, 8.18.
Preparation of 3,4,5-trimethoxy-2-(3,4-methylenedioxy-6-nitro-
phenyl)benzaldehyde (5): A 70% nitric acid solution (0.23 mL,
2.59 mmol) was added dropwise to a solution of carbaldehyde 17
(820 mg, 2.59 mmol) in acetic acid (20 mL). The mixture was
stirred at room temperature for 15 min and was poured onto ice.
The resulting precipitate was filtered, washed with saturated aq.
NaHCO3 solution and recrystallized from a ligroin/Et2O mixture to
afford 5 as a slightly colored solid (916 mg, 98%), mp (lig-
1
solid (500 mg, 89%), mp 89 °C. H NMR (300 MHz, CDCl3) ꢀ =
3.65 (s, 3 H), 3.85 (s, 3 H), 3.90 (s, 3 H), 4.10 (d, J = 9 Hz, 1 H),
4.30 (d, J = 9 Hz, 1 H), 6.15 (s, 1 H), 6.20 (s, 1 H), 6.80 (s, 1 H),
6.85 (s, 1 H), 7.65 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3) ꢀ =
32.1, 56.0, 60.9, 103.2, 105.5, 109.0, 111.4, 125.4, 127.0, 130.3,
142.2, 143.1, 147.7, 150.6, 151.3, 153.6 ppm. Anal. Calcd for
C17H16BrNO8: C, 47.91; H, 3.78; N, 3.29. Found: C, 47.99; H,
4.01; N, 3.38.
[14]
[17]
Preparation of 2,3-(methylenedioxy)-8,9,10-trimethoxyphenanthri-
dine (20): A solution of 5 (73 mg, 0.46 mmol) in MeOH (12 mL)
was hydrogenated for 1 h under pressure (3 bars) and in the pres-
ence of washed Raney nickel. The reaction mixture was solubilized
with CH2Cl2 (5 mL) and filtered through a pad of Celite which was
rinsed using 3 ꢀ 2 mL of a CH2Cl2/AcOEt mixture (1:1) to afford
1
20 as a white solid (47 mg, 75%), mp 197 °C (MeOH). H NMR
(300 MHz, CDCl3) ꢀ = 4.05 (2s, 6 H), 4.10 (s, 3 H), 6.15 (s, 2 H),
7.20 (s, 1 H), 7.55 (s, 1 H), 8.80 (s, 1 H), 9.05 (s, 1 H) ppm. 13C
NMR (75 MHz, CDCl3) ꢀ = 56.1, 60.5, 61.3, 101.7, 103.5, 104.7,
107.1, 119.1, 122.3, 123.4, 141.1, 146.3, 148.2, 148.3, 149.8,
150.8, 153.1 ppm. Anal. Calcd for C17H15NO5: C, 65.17; H, 4.83;
N, 4.47. Found: C, 64.79; H, 5.08; N, 4.28.
(a) Moreno, I.; Tellitu, I.; Etayo, J.; SanMartín, R.; Domínguez, E.
Novel applications of hypervalent iodine: PIFA mediated synthesis
of benzo[c]phenanthiridines and benzo[c]phenanthridinones. Tet-
rahedron, 2001, 57, 5403-5411; (b) Bunnell, A.E.; Flippin, L.A.;
Liu, Y. Total Synthesis of (±)-Roserine. J. Org. Chem., 1997, 62,
9305-9313.
1
roin/Et2O) 126 °C. H NMR (300 MHz, CDCl3) ꢀ = 3.70 (s, 3 H),
4.00 (s, 6 H), 6.20 (s, 2 H), 6.70 (s, 1 H), 7.35 (s, 1 H), 7.70 (s, 1
H), 9.70 (s, 1 H) ppm. 13C NMR (75 MHz, CDCl3) ꢀ = 56.2, 61.0,
103.3, 105.5, 106.4, 112.0, 125.3, 128.9, 129.8, 143.5, 147.2,
148.0, 150.3, 151.3, 153.7, 189.7 ppm. Anal. Calcd for C17H15NO8:
C, 56.51; H, 4.18; N, 3.88. Found: C, 56.41; H, 4.05; N, 3.88.
Gurjar, M.K.; Cherian, J.; Ramana, C.V. Synthesis of the putative
structure of eupomatilone-6. Org. Lett., 2004, 6, 317-319.
Preparation of 3,4,5-trimethoxy-2-(3,4-methylenedioxy-6-nitro-
phenyl)bromomethylbenzene (19): To a stirred suspension of car-
baldehyde 5 (500 mg, 1.38 mmol) in MeOH (50 mL), was added
NaBH4 (105 mg, 2.76 mmol). The mixture was stirred at room
[18]
[15]
[16]