Carba-Betti Strategy to Alkylidene Heterodimers
H), 3.23 (d, J = 6.3 Hz, 2 H, 1ЈЈЈ-H), 2.62 (s, 3 H, 1ЈЈ-acetyl), 2.58
(q, J = 7.6 Hz, 2 H, 6-Et), 1.90 (s, 3 H, 5-Me), 1.72 (br. s, 3 H,
4ЈЈЈ-H), 1.62 (br. s, 3 H, 5ЈЈЈ-H), 1.21 (t, J = 7.6 Hz, 6-Et) ppm.
13C NMR (75 MHz, CD3OD): δ = 204.4, 161.9, 159.8, 159.3, 140.4,
129.6, 127.5, 126.9, 124.9, 124.0, 112.7, 109.8, 108.5, 105.9, 32.2,
24.9, 24.2, 21.6, 16.8, 11.0, 9.1 ppm. CI-EI-MS: m/z = 479 [M +
H]+. C28H30O7 (478.53): calcd. C 70.28, H 6.32; found C 70.35, H
6.38.
31.6 (d), 29.0 (t), 28.7 (t), 24.3 (t), 22.6 (t), 14.0 (q), 11.6 (q), 11.6
(q), 9.5 (q), 9.4 (q) ppm. CI-EI-MS: m/z = 405 [M + H]+. C23H32O6
(404.50): calcd. C 68.29, H 7.97; found C 68.31, H 7.99.
6-Diethyl-1Ј-hexyl-6-methylhelipyrone (10f, 68%): Yellow powder;
m.p. 91 °C. IR (KBr): ν = 2957, 2922, 2854, 2680, 1677, 1572, 1260,
˜
1
1101, 1021, 806 cm–1. H NMR (300 MHz, CDCl3): δ = 11.40 (br.
s, 2 H, OH), 5.96 (s, 1 H, 5-H), 5.91 (s, 1 H, 5-H), 4.10 (t, J =
7.6 Hz, 1 H, 1Ј-H), 2.19 (s, 6 H, 6-Me), 2.14 (m, 2 H, 2Ј-H), 1.20
(m, 8 H, 3Ј-H, 4Ј-H, 5Ј-H, 6Ј-H), 0.80 (t, J = 6.7 Hz, 3 H, 7Ј-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 169.2 (s), 168.7 (s), 161.3
(s), 160.6 (s), 104.7 (s), 103.6 (d), 102.8 (d), 31.7 (t), 31.6 (d), 29.0
(t), 28.61 (t), 28.1 (t), 22.6 (t), 19.6 (q), 14.0 (q) ppm. CI-EI-MS:
m/z = 349 [M + H]+. C19H24O6 (348.39): calcd. C 65.50, H 6.94;
found C 65.53, H 6.92.
6-Diethyl-5,5,6-trimethyl-1Ј-phenylarzanol (4h, Procedure B: 30%):
Orange powder; m.p. 59 °C. IR (KBr): ν = 2965, 1673, 1613, 1433,
˜
1366, 1263, 1099, 800, 733, 697 cm–1. 1H NMR (300 MHz, CDCl3):
δ = ca. 7.20 (m, 3 H, 1Ј-Ph), 7.11 (d, 2 H, 1Ј-Ph), 6.02 (s, 1 H, 5-
H), 5.25 (t, J = 6.3 Hz, 2ЈЈЈ-H), 3.48 (s, 1 H, 1Ј-H), 3.45 (d, J =
6.3 Hz, 2 H, 1ЈЈЈ-H), 2.69 (s, 3 H, 1ЈЈ-acetyl), 2.27 (s, 3 H, 6-Me),
1.90 (s, 3 H, 5-Me), 1.84 (br. s, 3 H, 4ЈЈЈ-H), 1.79 (br. s, 3 H, 5ЈЈЈ-
H) ppm. 13C NMR (75 MHz, CD3OD): δ = 204.6, 177.0, 161.7,
137.3, 137.0, 128.5, 126.8, 126.5, 121.7, 107.3, 32.8, 31.2, 26.1, 22.5,
20.9, 19.8, 18.2 ppm. CI-EI-MS: m/z = 451 [M + H]+. C26H26O7
(450.48): calcd. C 69.32, H 5.82; found C 69.24, H 5.80.
1Ј-Phenylhelipyrone (10g, 52%): Yellowish powder; m.p. 130 °C. IR
(KBr): ν = 2977, 2937, 2876, 2756, 2607, 1673, 1614, 1555, 1354,
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1
1054, 804, 779, 711 cm–1. H NMR (300 MHz, CDCl3): δ = 11.46
(s, 1 H, OH), 11.20 (br. s, 1 H, OH), ca. 7.29 (m, 3 H, 1Ј-Ph), 7.15
(d, J = 8.0 Hz, 1Ј-Ph), 5.79 (s, 1 H, 1Ј-H), 2.61 (q, J = 7.6 Hz, 4
H, 6-Et), 2.02 (s, 3 H, 5-Me), 1.95 (s, 3 H, 5-Me), 1.23 (br. t, J =
7.6 Hz, 6 H, 6-Et) ppm. 13C NMR (75 MHz, CDCl3): δ = 162.1
(s), 161.5 (s), 135.8 (s) 128.5 (d), 126.6 (d), 109.7 (s), 109.1 (s), 104.4
(s), 103.0 (s), 35.5 (d), 24.5 (t), 11.6 (q), 9.65 (q), 9.5 (q) ppm. CI-
EI-MS: m/z = 397 [M + H]+. C23H24O6 (396.43): calcd. C 69.68,
H 6.10; found C 69.62, H 6.13.
Homodimerization of 4-Hydroxypyrones. Synthesis of Helipyrone
(10a): To a stirring solution of 1 (200 mg, 1.3 mmol, 1 equiv.) in
CHCl3 (3 mL) was added paraformaldehyde (19.5 mg, 0.65 mmol,
0.5 equiv.). The mixture was stirred at 40 °C and its progress was
monitored by TLC. After 16 h, the reaction mixture was evapo-
rated, and the residue was purified by GCC on silica gel (PE/
EtoAc, 7:3 as eluant) to afford 10a as a pale yellow solid (142 mg,
68%).
6-Diethyl-1Ј-phenyl-6-methylhelipyrone (10h, 55%): Yellowish pow-
der; m.p. 150 °C. IR (KBr): ν = 2985, 2905, 2760, 1680, 1614, 1548,
˜
1495, 1283, 1054, 779, 731 cm–1. 1H NMR (300 MHz, CDCl3): δ
= 7.27 (m, 3 H, 1Ј-Ph), 7.15 (d, J = 7.3 Hz, 2 H, 1Ј-Ph), 6.05 (br.
s, 2 H, 5-H), 5.77 (s, 1 H, 1Ј-H), 2.27 (s, 6 H, 6-Me) ppm. 13C
NMR (75 MHz, CDCl3): δ = 168.9 (s), 161.0 (s), 135.5 (s), 128.6
(d), 126.8 (d), 126.53 (d), 105.8 (d), 31.7 (t), 34.9 (d), 19.8 (q) ppm.
CI-EI-MS: m/z = 341 [M + H]+. C19H16O6 (340.23): calcd. C 67.05,
H 4.74; found C 67.11, H 4.70.
6-Diethyl-6-methylhelipyrone (10b, 63%): Yellowish powder; m.p.
165 °C. IR (KBr): ν = 3085, 2925, 2854, 2771, 2672, 1685, 1577,
˜
1350, 1237, 1174, 991, 859, 825, 525 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 10.73 (s, 2 H, 2ϫ OH), 5.99 (s, 2 H, 5-H), 3.5 (s, 2 H,
1Ј-H), 2.23 (s, 6 H, 6-Me) ppm. 13C NMR (75 MHz, CDCl3): δ =
168.7 (s), 161.3 (s), 102.7 (d), 101.7 (s), 19.9 (q), 18.6 (t) ppm. CI-
EI-MS: m/z = 265 [M + H]+. C13H12O6 (264.23): calcd. C 59.09,
H 4.58; found C 58.99, H 4.56.
Methylenebis(3-prenylphloracetophenone) (12a, 38%): To a stirring
solution of Eschenmoser’s salt (7.5 mg, 0.055 mmol, 0.5 equiv.) in
CHCl3 (1.5 mL) were sequentially added 7 (50 mg, 0.11 mmol,
1 equiv.) and TBAF (1 m in THF, 220 μL, 0.22 mmol, 2 equiv.). The
reaction was stirred at 40 °C and its progress was monitored by
TLC. After 16 h, the reaction was quenched by the addition of 2n
H2SO4 and extracted into CH2Cl2. The combined organic phases
were dried, filtered, and the solvents evaporated. The residue was
purified by GCC on silica gel (PE acidified with AcOH as eluant)
to afford 11a as a pale yellow solid (10 mg, 38%); m.p. 175 °C. IR
1Ј-Methylhelipyrone (10c, 65%): Yellowish powder; m.p. 125 °C. IR
(KBr): ν = 2967, 2860, 2781, 1670, 1579, 1365, 1231, 1165, 991,
˜
825, 560 cm–1. 1H NMR (300 MHz, CDCl3): δ = 4.36 (q, J =
7.3 Hz, 1 H, 1Ј-H), 2.47 (q, J = 7.3 Hz, 4 H, 6-Et), 1.87 (s, 6 H, 5-
Me), 1.63 (d, J = 7.3 Hz, 3 H, 2Ј-H), 1.12 (t, J = 7.3 Hz, 6 H, 6-
Et) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.2 (s), 169.9 (s),
169.0 (s), 168.8 (s), 168.5 (s), 161.5 (s), 160.8 (s), 109.7 (s), 109.0
(s), 105.8 (s), 105.77 (s), 27.1 (q), 26.13 (t), 14.5 (q), 11.6 (q) ppm.
CI-EI-MS: m/z = 335 [M + H]+. C18H22O6 (334.36): calcd. C 64.66,
H 6.63; found C 64.79, H 6.65.
(KBr): ν = 3291, 2920, 2853, 1621, 1566, 1435, 1282, 1118, 802,
˜
1
644 cm–1. H NMR (300 MHz, CD3OD): δ = 5.04 (t, J = 5.8 Hz,
6-Diethyl-1Ј,6-dimethylhelipyrone (10d, 60%): Yellowish powder;
2 H, 2ЈЈ-H), 3.69 (s, 2 H, 1Ј-H), 3.24 (d, J = 6.4 Hz, 2 H, 1ЈЈ-H),
2.63 (s, 6 H, 1-acetyl), 1.69 (br. s, 6 H, 4ЈЈ-H), 1.59 (br. s, 6 H, 5ЈЈ-
H) ppm. 13C NMR (75 MHz, CD3OD): δ = 204.8, 160.3, 160.2,
158.3, 131.3, 123.7, 109.3, 107.1, 106.8, 33.3, 26.2, 22.3, 20.0, 18.6,
17.6, 14.2 ppm. CI-EI-MS: m/z = 485 [M + H]+. C27H32O8
(484.54): calcd. C 66.93, H 6.66; found C 67.03, H 6.72.
m.p. 110 °C. IR (KBr): ν = 2943, 2900, 2667, 1650, 1635, 1332,
˜
1229, 1101, 1046, 967, 716 cm–1. 1H NMR (300 MHz, CDCl3): δ
= 5.94 (s, 1 H, 5-H), 4.34 (q, J = 7.6 Hz, 1 H, 1Ј-H), 2.20 (s, 6 H,
6-Me), 1.64 (d, J = 7.6 Hz, 3 H, 2Ј-H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 170.7 (s), 161.5 (s), 107.6 (s), 103.2 (d), 27.5 (d), 21.60
(q), 16.49 (q) ppm. CI-EI-MS: m/z = 279 [M + H]+. C14H14O6
(278.26): calcd. C 60.43, H 5.07; found C 60.49, H 5.03.
Ethylidenebis(3-prenylphloracetophenone) (12b, 40%): Yellowish
powder; m.p. 104 °C. IR (KBr): ν = 3517, 3323, 2976, 2931, 1630,
˜
1Ј-Hexylhelipyrone (10e, 66%): Yellowish powder, m.p. 85 °C. IR
1600, 1452, 1362, 791, 650 cm–1. 1H NMR (300 MHz, CDCl3): δ
= 5.20 (t, J = 7.0 Hz, 2 H, 2ЈЈ-H), 4.83 (q, J = 7.7 Hz, 1 H, 1 H,
1
(KBr): ν = 2927, 2856, 1667, 1607, 1560, 1324, 802, 776 cm–1. H
˜
NMR (300 MHz, CDCl3): δ = 11.87 (s, 1 H, OH), 11.04 (br. s, 1 1Ј-H), 3.40 (d, J = 6.7 Hz, 4 H, 1ЈЈ-H), 2.66 (s, 6 H, 1-acetyl), 1.83
H, OH), 4.10 (t, J = 7.6 Hz, 1Ј-H), 2.47 (br. m, 4 H, 6-Et), 2.11
(br. s, 6 H, 4ЈЈ-H), 1.78 (br. s, 6 H, 5ЈЈ-H), 1.77 (d, J = 7.3 Hz, 2Ј-
(m, 2 H, 2Ј-H), 1.88 (s, 3 H, 5-Me), 1.85 (s, 3 H, 5-Me), ca. 1.11 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 204.7, 160.8, 160.6,
(m, 6 H, 3Ј-H, 4Ј-H, 5Ј-H), 0.77 (q, J = 6.7 Hz, 3 H, 6Ј-H) ppm. 158.4, 137.1, 121.7, 110.1, 106.3, 104.9, 33.0, 31.2, 30.0, 26.1, 24.8,
13C NMR (75 MHz, CDCl3): δ = 170.1 (s), 169.4 (s), 168.8 (s),
22.4, 19.2, 17.5 ppm. CI-EI-MS: m/z = 499 [M + H]+. C28H34O8
168.4 (s), 161.5 (s), 160.8 (s), 109.5 (s), 108.9 (s), 104.7 (s), 32.2 (t),
(498.56): calcd. C 67.45, H 6.87; found C 67.29, H 6.83.
Eur. J. Org. Chem. 2012, 772–779
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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