C. M. Williams et al. / Tetrahedron 61 (2005) 3771–3779
3775
added rapidly. After addition the flask was taken out of the
bath and stirred at room temperature for 1 h. The reaction
mixture was then transferred, via Pasteur pipette, to a
separatory funnel containing a saturated solution of sodium
hydrogen carbonate (50 mL) and extracted with dichloro-
methane (3!10 mL). The residue was dried under vacuum,
redissolved in anhydrous THF (3 mL) and sodium hydride
added until effervescence ceased. The mixture was
quenched with saturated ammonium chloride solution and
extracted with dichloromethane (3!10 mL). Column
chromatography (ethyl acetate/dichloromethane, 5:95)
afforded the title compound as a bright yellow viscous oil
the residue suspended in dichloromethane (5 mL) and
passed through celite. Column chromatography (diethyl
ether/light petroleum, w1:4) of the residue on silica gel
afforded the title compound (0.159 g, 93%) and 22 (0.004 g,
3%) both as pale yellow oils. 1H NMR (400 MHz, CHCl3) d
1.22–1.30 (m, 9H), 1.54–1.63 (m, 1H), 1.96–2.05 (m, 1H),
2.17 (s, 3H), 2.36–2.49 (m, 2H), 2.51–2.60 (m, 1H), 2.79
(dd, JZ10.7, 2.4 Hz, 1H), 2.87 (dd, JZ11.1, 2.4 Hz, 1H),
2.89–3.03 (m, 1H), 2.97 (dd, JZ11.1, 1.3 Hz, 1H), 3.28 (dd,
JZ10.7, 1.3 Hz, 1H), 3.82 (s, 3H), 4.13–4.25 (m, 2H), 4.59
(sept, JZ6.2 Hz, 1H), 6.99–7.07 (m, 2H), 7.42 (AB, 1H).
13C NMR (100 MHz, CDCl3) d 14.1, 22.3, 22.4, 23.6, 35.9,
44.8, 46.2, 54.9, 56.1, 61.2, 63.1, 65.4, 71.3, 76.1, 116.1,
122.8, 123.7, 125.7, 134.3, 142.4, 147.0, 153.5, 172.7,
195.3. Near IR (Nujol) n (cmK1) 1729, 1713, 1681, 1666.
MS m/z (EI) 494 (MC%, 0.5%), 492 (MC%, 0.5%), 414 (77),
368 (7), 354 (7), 340 (2), 326 (9), 315 (1), 302 (11), 300
(12), 283 (2), 256 (2), 220 (27), 208 (5), 206 (8), 193 (49),
174 (2), 151 (100), 148 (6), 146 (5), 134 (6), 120 (4). Anal.
Calcd for C24H32BrNO5: MC% 414.2280 (KHBr). Found:
414.2277.
1
(0.13 g, 70%). H NMR (400 MHz, CHCl3) d 0.83 (t, JZ
7.1 Hz, 3H), 1.56–1.65 (m, 1H), 2.20 (s, 3H), 2.21–2.28 (m,
2H), 2.40–2.51 (m, 1H), 2.63 (d, JZ11.1 Hz, 1H), 2.69–
2.76 (m, 1H), 2.85 (dd, JZ10.6, 2.4 Hz, 1H), 2.93–3.07 (m,
2H), 3.50 (dd, JZ10.6, 1.3 Hz, 1H), 3.66–3.85 (m, 2H),
3.89 (s, 3H), 6.87 (t, JZ8.1 Hz, 1H), 7.03–7.07 (m, 1H),
7.38 (s, 1H), 7.42 (dd, JZ8.1, 1.4 Hz, 1H), 12.26 (s, OH).
13C NMR (100 MHz, CDCl3) d 13.3, 23.6, 36.3, 44.6, 47.3,
52.4, 56.2, 60.9, 64.1, 71.1, 71.5, 117.1, 118.4, 120.1, 122.6,
123.0, 148.7, 152.7, 153.0, 172.3, 199.5. MS m/z (EI) 453
(MC%, 4%), 451 (MC%, 5%), 408 (2), 406 (2), 372 (80), 326
(20), 302 (20), 300 (21), 298 (14), 286 (6), 283 (6), 279 (15),
256 (8), 222 (17), 220 (30), 206 (19), 167 (39), 151 (98), 149
(100), 129 (11), 113 (18). Anal. Calcd for C21H26BrNO5:
MC% 451.0995. Found: 451.0989.
4.2.4. Pyranones 22 and 23. Ethyl 5-bromo-3-methyl-9-[2-
oxo-2-(2-hydroxy-3-methoxyphenyl)-E-ethylidene]-3-aza-
bicyclo[3.3.1]nonanecarboxylate 16 (0.023 g, 0.051 mmol)
was dissolved in N,N-dimethylformamide (2.0 mL) fol-
lowed by addition of potassium carbonate (0.021 g,
0.15 mmol). The mixture was then heated at 80 8C for
15 min. On cooling N,N-dimethylformamide was removed
under high vacuum and the residue suspended in dichloro-
methane (5 mL) and passed through celite. Column
chromatography (dichloromethane/ethyl acetate, gradient)
of the residue on silica gel afforded two fractions. Fraction
one (22) (6 mg, 26%) was obtained as colourless crystals.
4.2.2. Photolysis of ethyl 5-bromo-3-methyl-9-[2-oxo-2-
(2-hydroxy-3-methoxyphenyl)-E-ethylidene]-3-azabi-
cyclo[3.3.1]nonanecarboxylate 16. Ethyl 5-bromo-3-
methyl-9-[2-oxo-2-(2-hydroxy-3-methoxyphenyl)-E-ethyl-
idene]-3-azabicyclo[3.3.1]nonanecarboxylate 16 (0.020 g,
0.044 mmol) was dissolved in oxygen free D7-N,N-
dimethylformamide (1 mL) in a 5 mm NMR tube (PP-
528) and irradiated with a Hanovia high pressure mercury–
xeon vapour lamp (1000 W). [Note. The light was passed
through a w5 8C water filter (30 cm long) and the sample
placed 10 cm from the end of the cooling tube.] The
1
Mp 116–118 8C (diethyl ether/dichloromethane) H NMR
(400 MHz, CHCl3) d 0.89 (t, JZ7.2 Hz, 3H), 1.63–1.78 (m,
2H), 2.22 (s, 3H), 2.31–2.38 (m, 1H), 2.67–2.97 (m, 5H),
3.15–3.27 (m, 2H), 3.34 (d, JZ14.7 Hz, 1H), 3.52–3.73 (m,
3H), 3.88 (s, 3H), 6.86 (t, JZ8.0 Hz, 1H), 7.03 (dd, JZ8.0,
1.6 Hz, 1H), 7.37 (dd, JZ8.0, 1.6 Hz, 1H). 13C NMR
(100 MHz, CDCl3) d 13.4, 23.2, 29.4, 39.0, 41.3, 44.7, 52.8,
56.7, 59.7, 61.3, 65.5, 74.6, 83.1, 117.2, 117.9, 120.1, 120.4,
149.3, 150.7, 172.2, 189.8. MS m/z (EI) 453 (MC%, 30%),
451 (MC%, 32%), 408 (8), 372 (74), 328 (46), 315 (7), 298
(34), 283 (14), 270 (4), 255 (27), 220 (27), 151 (57), 138
(17), 136 (21), 122 (21), 105 (13). Anal. Calcd for
C21H26BrNO5: MC% 451.0995. Found: 451.0992. Fraction
two (23) (14 mg, 61%) was obtained as colourless needles.
1
isomerization was monitored by H NMR every 15 min
until a 1:1 mixture of 16 and 21 was evident. The solvent
was removed and the residue subjected to column
chromatography (dichloromethane) affording an insepar-
able 1:1 mixture of 16 and 21 (0.015 g, 75%).
The relevant 1H NMR values for 21 are listed only and are
a result from subtracting isolated peaks observed from a
spectrum of pure 16.
1
Mp 131–133 8C (diethyl ether/dichloromethane) H NMR
1H NMR (200 MHz, CHCl3) d 1.27 (t, JZ7.4 Hz, 3H), 3.32
(AB, 1H), 3.885 (s, 3H), 4.12–4.26 (m, 2H), 5.80 (s, 1H).
(400 MHz, CHCl3) d 0.94 (t, JZ7.2 Hz, 3H), 1.48–1.58 (m,
1H), 1.84 (dd, JZ14.9 Hz, 6.5, 1H), 2.26 (s, 3H), 2.32–2.48
(m, 3H), 2.72 (d, JZ11.6 Hz, 1H), 2.85–3.02 (m, 1H), 3.16
(d, JZ10.8 Hz, 1H), 3.32 (dd, JZ11.6, 2.6 Hz, 1H), 3.47–
3.65 (m, 5H), 3.88 (s, 3H), 6.86 (t, JZ7.9 Hz, 1H), 7.01 (dd,
JZ7.9, 1.5 Hz, 1H), 7.38 (dd, JZ7.9, 1.5 Hz, 1H). 13C
NMR (100 MHz, CDCl3) d 13.4, 22.7, 32.1, 39.8, 40.5,
45.1, 52.3, 56.8, 57.7, 61.2, 64.4, 74.8, 83.1, 117.1, 117.9,
120.2, 120.6, 149.3, 149.9, 172.3, 189.9. MS m/z (EI) 453
(MC%, 30%), 451 (MC%, 29%), 372 (43), 328 (27), 298 (14),
283 (10), 255 (13), 227 (4), 220 (7), 194 (6), 151 (32), 138
(10), 136 (9), 122 (11), 105 (6). Anal. Calcd for
C21H26BrNO5: C, 55.76; H, 5.79; N, 3.10; MC% 451.0995.
Found: C, 55.53; H, 5.76; N, 3.07; MC% 451.0986.
4.2.3. Ethyl 5-bromo-3-methyl-9-[2-oxo-2-(2-isopro-
poxy-3-methoxyphenyl)-E-ethylidene]-3-azabicyclo-
[3.3.1]nonanecarboxylate 14. Ethyl 5-bromo-3-methyl-9-
[2-oxo-2-(2-hydroxy-3-methoxyphenyl)-E-ethylidene]-3-
azabicyclo[3.3.1]nonanecarboxylate
16
(0.156 g,
0.345 mmol) was dissolved in N,N-dimethylformamide
(1.5 mL) followed by addition of 2-bromopropane
(0.97 mL, 10.3 mmol) and potassium carbonate (0.095 g,
0.69 mmol). The mixture was then stirred at room
temperature for 16 h. Excess 2-bromopropane and N,N-
dimethylformamide were removed under high vacuum and