Organic & Biomolecular Chemistry
Paper
column chromatography (silica gel, hexane) to afford 0.57 g (s, P–O–C) cm−1. HRMS (ESI+): calcd for C19H29NaO3P ([M +
(93%) of a pale yellow oil identified as trimethyl[(2,6,6-tri- H]+), 359.1747; found, 359.1745.
methylcyclohexa-1,3-dien-1-yl)ethynyl]silane 22. 1H NMR
(3R,3′R)-Alloxanthin 1. To a cooled (−78 °C) solution of
(400.13 MHz, CDCl3): δ 5.86 (dt, J = 9.6, 1.5 Hz, 1H, H3), 5.80 (R,E)-4-[5-(diethoxyphosphoryl)-3-methylpent-3-en-1-ynyl]-3,5,5-
(dt, J = 9.6, 4.2 Hz, 1H, H4), 2.09 (dd, J = 4.2, 1.5 Hz, 2H, 2H5), trimethylcyclohex-3-enyl acetate 19 (28 mg, 0.070 mmol) in
1.95 (s, 3H, CH3), 1.07 (s, 6H, 2 × CH3), 0.21 (s, 9H, 3 × CH3). THF (0.9 mL) was added NaHMDS (0.08 mL, 1 M in hexane,
13C NMR (100.62 MHz, CDCl3): δ 137.6 (s), 127.7 (d), 126.8 (d), 0.08 mmol). After stirring for 30 min, a solution of (2E,4E,6E)-
123.6 (s), 103.8 (s), 101.7 (s), 38.2 (t), 32.4 (s), 27.0 (q, 2×), 20.7 2,7-dimethylocta-2,4,6-triene-1,8-dial 8d (5.2 mg, 0.032 mmol)
(q), 0.2 (q, 3×). IR (NaCl): ν 2958 (s, C–H), 2128 (s, CuC), 859 in THF (1.1 mL) was added. After stirring for 2 h at the same
(s, Si–C), 842 (s, Si–C) cm−1. HRMS (ESI+): calcd for C14H23Si temperature a saturated aqueous solution of NH4Cl was added
([M + H]+), 219.1564; found, 219.1569.
and the mixture was extracted with a 90 : 10 EtOAc–CH2Cl2
1-Ethynyl-2,6,6-trimethylcyclohexa-1,3-diene
23. To
a
mixture. The combined organic layers were washed with a satu-
solution of trimethyl[(2,6,6-trimethylcyclohexa-1,3-dien-1-yl)- rated aqueous solution of NaHCO3, dried (Na2SO4) and the
ethynyl]silane 22 (0.53 g, 2.42 mmol) in THF (24 mL) was solvent was evaporated. The residue was used in the next reac-
added TBAF (3.63 mL, 1 M in hexane, 3.63 mmol). After stir- tion without further purification. To a cooled (−15 °C) solution
ring for 40 min at 25 °C the reaction mixture was poured over of alloxanthin acetate (0.021 g, 0.032 mmol) in Et2O (0.5 mL)
a saturated aqueous NaHCO3 solution and extracted with Et2O was added MeLi (0.1 mL, 1.6 M, 0.16 mmol) and the mixture
(3×). The combined organic layers were dried (Na2SO4) and the was stirred for 30 min at the same temperature. Then the
solvent was evaporated. Purification by column chromato- mixture was warmed to 25 °C and a solution of saturated
graphy (silica gel, hexane) afforded 0.28 g (79%) of a yellow oil aqueous solution of NaHCO3 was added. The mixture was
identified as 1-ethynyl-2,6,6-trimethylcyclohexa-1,3-diene 23. extracted with a 90 : 10 EtOAc–CH2Cl2 mixture, dried (Na2SO4)
1H-NMR (400.13 MHz, CDCl3): δ 5.87 (dt, J = 9.6, 1.4 Hz, 1H, and the solvent was evaporated. The residue was purified by
H3), 5.83 (dt, J = 9.6, 4.0 Hz, 1H, H4), 3.32 (s, 1H), 2.11 (dd, J = column chromatography (C18 silica gel, CH3CN) to afford
4.0, 1.4 Hz, 2H, 2H5), 1.96 (s, 3H, C2–CH3), 1.09 (s, 6H, 2 × C6– 14 mg (78%) of a red solid identified as (3R,3′R)-alloxanthin 1.
CH3). 13C-NMR (100.62 MHz, CDCl3): δ 138.1 (s), 127.6 (d), 1H-NMR (400.13 MHz, C6D6): δ 6.79 (d, J = 11.4 Hz, 2H, 2H10),
126.9 (d), 122.6 (s), 110.0 (s), 84.1 (d), 38.1 (t), 32.4 (s), 26.9 (q, 6.64–6.55 (m, 4H, 2H11 + 2H14), 6.36 (d, J = 14.8 Hz, 2H, 2H12),
2×), 20.5 (q). IR (NaCl): ν 3306 (s, CuC–H), 2958 (s, C–H), 2920 6.27–6.24 (m, 2H, 2H15), 3.75–3.68 (m, 2H, 2H3), 2.16 (dd, J =
(s, C–H), 2859 (s, C–H), 2080 (w, CuC) cm−1
.
18.2, 5.1 Hz, 2H, 2H4), 1.98 (s, 6H, 2 × CH3), 1.92 (s, 6H, 2 ×
CH3), 1.88 (dd, J = 18.2, 8.3 Hz, 2H, 2H4), 1.79 (s, 6H, 2 × CH3),
1.65 (ddd, J = 12.2, 3.2, 1.7 Hz, 2H, 2H2), 1.39 (d, J = 12.0 Hz,
2H, 2H2), 1.35 (s, 6H, 2 × CH3), 1.23 (s, 6H, 2 × CH3) ppm.
Diethyl (E)-[3-methyl-5-(2,6,6-trimethylcyclohexa-1,3-dien-1-yl]-
pent-2-en-4-yn-1-yl)phosphonate 24
To a degassed solution of Pd(PPh3)4 (14.0 mg, 0.01 mmol) in 13C-NMR (100.62 MHz, C6D6): δ 138.5 (d, 2×), 137.8 (s, 2×),
THF (1.4 mL) was added CuI (6.8 mg, 0.036 mmol) and a solu- 136.7 (s, 2×), 135.7 (d, 2×), 134.1 (d, 2×), 130.9 (d, 2×), 124.8 (s,
tion of 18 (127 mg, 0.40 mmol) in THF (2.8 mL) via cannula. 2×), 124.7 (d, 2×), 119.7 (s, 2×), 99.2 (s, 2×), 90.2 (s, 2×), 64.5 (d,
To the described mixture was added Et3N (0.14 mL, 2×), 47.0 (t, 2×), 41.7 (t, 2×), 36.8 (s, 2×), 30.9 (q, 2×), 29.0 (q,
1.00 mmol) and a solution of 1-ethynyl-2,6,6-trimethylcyclo- 2×), 22.7 (q, 2×), 18.3 (q, 2×), 12.9 (q, 2×) ppm. HRMS (ESI+):
hexa-1,3-diene 23 (87.6 mg, 0.60 mmol) in THF (2.8 mL). The calcd for C40H53O2 ([M + H]+), 565.4040; found, 565.4039.
reaction mixture was stirred for 2 h 30 min at 25 °C. Then it [α]2D4 −106.0 (c 0.01, CHCl3).
was filtered with AcOEt through a pad of Celite® and the
solvent was evaporated. The residue was purified by column
3,4,7,8,3′,4′,7′,8′-Octadehydro-β,β-carotene 2
chromatography (C-18 silica gel, from 65 : 35 to 100 : 0 CH3CN– To a cooled (−78 °C) solution of diethyl (E)-[3-methyl-5-(2,6,6-
H2O) to afford 88.8 mg (66%) of a pale yellow oil identified as trimethylcyclohexa-1,3-dien-1-yl]pent-2-en-4-yn-1-yl)phosphonate
diethyl (E)-[3-methyl-5-(2,6,6-trimethylcyclohexa-1,3-dien-1-yl]- (C15-alkynylphosphonate) 24 (24.5 mg, 0.07 mmol) in THF
pent-2-en-4-yn-1-yl)phosphonate 24. 1H-NMR (400.13 MHz, (1 mL) was added NaHMDS (0.083 mL, 1 M in hexane,
C6D6): δ 6.12–6.00 (m, 1H, H4′), 5.79 (dt, J = 9.5, 1.7 Hz, 1H, 0.08 mmol). After stirring for 30 min, a solution of (2E,4E,6E)-
H3′), 5.63 (dt, J = 9.3, 4.5 Hz, 1H, H2), 3.97–3.83 (m, 4H, 2 × 2,7-dimethylocta-2,4,6-triene-1,8-dial 8d (5.4 mg, 0.03 mmol)
OCH2CH3), 2.49 (dd, J = 23.6, 8.3 Hz, 2H, 2H1), 1.98 (dd, J = in THF (1 mL) was added. The mixture was stirred at −78 °C
4.5, 1.7 Hz, 2H, 2H5′), 1.96 (s, 3H, C2′–CH3), 1.82 (d, J = 4.5 Hz, for 1.5 h. Then, a saturated aqueous solution of NH4Cl was
3H, C3–CH3), 1.18 (s, 6H, 2 × C6–CH3), 1.01 (t, J = 6.9 Hz, 6H, added at −78 °C and the mixture was allowed to reach room
2 × OCH2CH3) ppm. 13C-NMR (100.62 MHz, C6D6): δ 136.3 (s, temperature and extracted with 90 : 10 EtOAc–CH2Cl2. The
2
JP–C = 2.0 Hz), 127.9 (d), 126.5 (d), 125.2 (d, JP–C = 12.8 Hz), combined organic layers were washed with
a
saturated
aqueous solution of NaHCO3, dried (Na2SO4) and the solvent
6.5 Hz), 87.2 (s, JP–C = 3.6 Hz), 61.7 (t, JP–C = 6.4 Hz), 38.5 (t), was evaporated. The crude was purified by column chromato-
124.6 (s, JP–C = 2.1 Hz), 123.0 (s, JP–C = 15.9 Hz), 100.4 (s, JP–C
=
1
33.2 (s), 27.9 (t, JP–C = 139.3 Hz), 20.4 (q, 2×), 17.9 (q, JP–C
=
graphy (silicagel-CN, from 100 : 0 to 90 : 10 hexane–EtOAc)
2.8 Hz), 16.5 (q, JP–C = 5.5 Hz, 2×) ppm. IR (NaCl): ν 2966 (s, afforded 8.2 mg (47%) of an orange solid identified as octade-
C–H), 2912 (s, C–H), 2865 (s, C–H), 1251 (m, PvO), 1050–1027 hydro-β,β-carotene 2. 1H-NMR (400.13 MHz, C6D6): δ 6.81 (d,
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Org. Biomol. Chem., 2015, 13, 3024–3031 | 3029