Organic & Biomolecular Chemistry
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(100), 471 [M + H − CO]+ (18), 453 [M + H − CO2]+ (89). HRMS [M + Na]+. HRMS (ES): observed 503.2626. C28H39O8 requires
+
(ES): observed 497.1821. C27H29O9+ requires 497.1806.
503.2639.
Isomer 1 (major): Rf (60% EtOAc–hexanes): 0.35. 1H NMR
Further elution with 60% EtOAc–hexanes gave 3,4-dimethyl-
CDCl3 (400 MHz) δ 6.33 (s, 2H, H5′), 5.59 (2H, s, H4/5), 3.89 (s, 1,6-bis(3,4,6-trimethoxy-2-methylphenyl)hexa-1,5-diene-3,4-diol
6H, OMe), 3.86 (s, 6H, OMe), 3.72 (s, 6H, C3′–OMe), 2.34 (s, (49) as a white solid (0.28 g, 22%), m.p. = 138–141 °C. Rf (60%
6H, C2′-Me). 13C NMR CDCl3 (150 MHz) δ 158.2 (C4′ or C6′), EtOAc–hexanes): 0.30; IR (thin film) νmax cm−1: 3200–3600 (OH.
155.0 (C4′ or C6′), 153.3 (C2), 141.2 (C3′), 136.5 (C2′), 102.2 1H NMR (600 MHz): δ 6.58 (d, J = 16.2 Hz, 2H, H6), 6.36 (s, 2H,
(C1′), 94.21 (C5′), 87.7 (C1″ or C2″), 86.32 (C1″ or C2″), 73.4 H5′), 6.26 (d, J = 16.2 Hz, 2H, H5), 3.86 (s, 6H, OMe), 3.71 (s,
(C4/5), 60.6 (C3′–OMe), 56.3 (OMe), 56.0 (OMe), 14.2 (C2′-Me).
12H, 2 × OMe), 2.48 (s, 6H, OH), 2.25 (s, 6H, C2′-Me), 1.45 (s,
Isomer 2 (minor): Rf (60% EtOAc–hexanes): 0.3; 1H NMR 6H, H3/4-Me). 13C NMR (100 MHz) δ 154.0 (C4′ or C6′), 151.9
CDCl3 (400 MHz) δ 6.28 (s, 2H, H5′), 5.77 (s, 2H, H4/5), 3.87 (s, (C4′ or C6′), 141.5 (C3′), 137.9 (C6), 131.3 (C1′ or C2′), 122.9
6H, OMe), 3.73 (s, 6H, OMe), 3.66 (s, 6H, C3′–OMe), 2.24 (s, (C5), 118.7 (C1′ or C2′), 95.1 (C5′), 78.2 (C4), 60.6 (OMe), 56.0
6H, C2′-Me). 13C NMR CDCl3 (100 MHz) δ 158.2 (C4′ or C6′), (OMe), 22.4 (C4-Me), 13.4 (C2′-Me). MS (ES) m/z: 541 [M + K]+
154.4 (C4′ or C6′), 153.1 (C2), 140.8 (C3′), 136.2 (C2′), 102.4 (100), 539 [M + K − H2]+ (20), 525 [M + Na]+ (50), 523 [M + Na −
(C1′), 93.7 (C5′), 87.5 (C1″ or C2″), 85.9 (C1″ or C2″), 71.3 H2]+ (35), 507 [M + Na − H2O] (10). HRMS (ES): observed
(C4/5), 60.2 (C3′–OMe), 55.8 (OMe), 55.6 (OMe), 13.8 (C2′-Me).
525.2468. C28H38O8Na+ requires 525.2459.
1,6-Bis(3,4,6-trimethoxy-2-methylphenyl)hexa-1,5-diyn-3,4-
dione (47)
3,4-Dimethyl-1,6-bis(3,4,6-trimethoxy-2-methylphenyl)hexa-1,5-
diyne-3,4-diol (34)
Ac2O (5 mL, 0.05 mol) was added to a stirred solution of 45 A flame dried Schlenk flask under argon was charged with
(0.69 g, 1.5 mmol) and DMSO (20 mL). After 5 h the reaction samarium metal (75 mg, 0.49 mmol), 1,2-diiodoethane
mixture was cooled to 0 °C and diluted with H2O (50 mL). The (65 mg, 0.23 mmol) and dry THF (4 mL), purging and back-
resulting precipitate was vacuum filtered to give an orange filling with argon after each addition. After 30 min of stirring
solid. The filtrate was diluted with 28% aqueous NH3 (8 mL), the reaction mixture containing SmI2 was treated with a solu-
then extracted with EtOAc (3 × 20 mL). The extract was washed tion of antrocamphin B (3) (63 mg, 0.25 mmol) in dry THF
with brine (20 mL), dried and evaporated and combined with (1 mL). After 2.5 h the reaction was quenched with H2O
the precipitate to give 47 as an orange solid (0.66 g, 90%), (20 mL) and the aqueous solution was extracted with EtOAc
m.p. = 231–235 °C. Rf (60% EtOAc–hexanes): 0.35; IR (thin (3 × 10 mL). The extract was washed with brine (10 mL), dried
film) νmax cm−1
:
2177 (CuC), 1662 (CvO). 1H NMR and evaporated, and the residue was subjected to flash
(600 MHz): δ 6.31 (s, 2H, H5′), 3.93 (s, 6H, OMe), 3.88 (s, 6H, chromatography. Elution with 60% EtOAc–hexanes gave 34
OMe), 3.73 (s, 6H, OMe), 2.47 (s, 6H, C2′-Me). 13C NMR (10 : 1 mixture of rac : meso isomers) (35 mg, 55%) as a pale
(150 MHz) δ 173.3 (CvO), 161.1 (C4′ or C6′), 157.3 (C4′ or C6′), yellow solid. IR (thin film) νmax cm−1: 3100–3700 (OH), 2222
141.3 (C3′), 138.6 (C2′), 100.8 (C1′), 98.0 (C1/6), 94.8 (C2/5); (CuC).
93.7 (C5′), 60.5 (OMe), 56.3 (OMe), 55.9 (OMe), 14.2 (C2′-Me).
The isomers were separated by semi-preparative HPLC
using a Hewlett Packard 1050 system equipped with a multiple
wavelength detector (MWD). Separation was achieved using a
250 × 10 mm i.d., 5 μm, Apollo C18 reversed phase column
(Grace-Davison) with a 33 mm × 7 mm guard column of the
HRMS (ES): observed, 467.1702. C26H27O8+ requires 467.1706.
Attempted pinacol coupling of antrocamphin B (3) with Zn/Cu
couple
Freshly prepared Cu/Zn couple45 (3.01 g, 1 : 1 –CuSO4· same material. The column was eluted at 4 mL min−1 with
5H2O : Zn w/w) and AcOH (1.5 mL, 26 mmol) were added to a 30% (v/v) acetonitrile–water and 1 mL was injected. The chiral
stirred solution of antrocamphin B (3) (1.21 g, 4.88 mmol) in isomers eluted first giving 34b as a white solid: m.p. =
THF (40 mL). After 30 h the reaction suspension was vacuum 126–130 °C. Rf (60% EtOAc–hexanes): 0.2. 1H NMR CDCl3
filtered through Celite and washed through with DCM (3 × (600 MHz) δ 6.30 (s, 2H, H5′), 3.86 (s, 6H, OMe), 3.81 (s, 6H,
15 mL). The filtrate was evaporated residue was subjected to OMe), 3.69 (s, 6H, OMe), 3.37 (s, 2H, OH), 2.33 (s, 6H, C2′-Me),
flash chromatography. Elution with 40% EtOAc–hexanes gave 1.72 (6H, s, C3/4-Me). 13C NMR CDCl3 (150 MHz) δ 157.9 (C4′
meso-4,5-bis(3,4,6-trimethoxy-2-methylphenyl)octane-2,7-dione or C6′), 153.8 (C4′ or C6′), 141.2 (C3′), 135.2 (C2′), 104.3 (C1′),
(50) as a pale yellow solid (92 mg, 8%), m.p. = 203–206 °C. Rf 97.3 (C1/6 or C2/5), 94.5 (C5′), 80.6 (C1/6 or C2/5), 75.3 (C3/4),
(60% EtOAc–hexanes): 0.35; IR (thin film) νmax cm−1: 1710 60.6 (OMe), 56.4 (OMe), 56.0 (OMe), 23.9 (C3/4-Me), 14.3
1
(CvO). H NMR (400 MHz): δ 6.35 (s, 2H, H5′), 4.20–4.22 (m, (C2′-Me).
2H, H3/6 or H4/5), 3.88 (s, 6H, OMe), 3.84 (s, 6H, OMe), 3.71
Further elution gave the mesoisomer 34a as a white solid:
(s, 6H, OMe), 2.97–3.03 (m, 2H, C3/6 or C4/5), 2.43 (s, 6H, C2′- m.p. = 138–142 °C. Rf (60% EtOAc–hexanes): 0.2. 1H NMR
Me), 2.22–2.27 (m, 2H, H3/6 or H4/5). 13C NMR (100 MHz) CDCl3 (600 MHz) δ 6.29 (s, 2H, H5′), 3.86 (s, 6H, OMe), 3.79 (s,
δ 209.2 (C2/7′), 154.8 (C4′ or C6′), 151.6 (C4′ or C6′), 141.1 6H, OMe), 3.69 (s, 6H, OMe), 3.23 (s, 2H, OH), 2.29 (s, 6H, C2′-
(C3′), 133.1 (C2′), 122.3 (C1′), 95.3 (C5′), 60.6 (OMe), 55.8 Me), 1.72 (s, 6H, C3/4-Me). 13C NMR CDCl3 (150 MHz) δ 157.9
(OMe), 55.7 (OMe), 45.9 (C3/6 or C4/5), 37.3 (C3/6 or C4/5), (C4′ or C6′), 153.7 (C4′ or C6′), 141.2 (C3′), 135.4 (C2′), 104.4
30.5 (C1/8), 14.2 (C2′-Me). MS (ES) m/z: 541 [M + K]+, 525 (C1′), 97.9 (C1/6 or C2/5), 94.5 (C5′), 80.4 (C1/6 or C2/5), 74.9
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Org. Biomol. Chem., 2014, 12, 1100–1113 | 1111