6-[(E)-2-Iodovinyl]-4-methoxy-3-methyl-2H-pyran-2-one (3).
A solution of aldehyde 7 (25 mg, 0.15 mmol) and CHI3 (117 mg,
0.30 mmol) in dioxane (1 mL) were added by syringe to a solution
of anhydrous CrCl2 (110 mg, 0.89 mmol) in tetrahydrofuran (THF)
(1 mL) at 0 °C under argon. The reaction mixture was stirred at 0
°C for 3 h, poured onto a large excess of water, and extracted with
Et2O. The combined organic extracts were washed with brine, dried
(MgSO4), and concentrated. The residue was purified by flash
chromatography (2% acetone/chloroform) to afford vinyl iodide 3
(28 mg, 64%) as an off-white solid: 1H NMR (400 MHz, CDCl3)
δ 7.48 (d, J ) 14.8 Hz, 1H), 7.83 (d, J ) 14.8 Hz, 1H), 4.90 (s,
1H), 3.88 (s, 3H), 1.91 (s, 3H); 13C NMR (63 MHz, CDCl3) δ
164.9, 164.1, 155.9, 135.8, 104.2, 95.7, 86.6, 56.3, 8.9; IR (KBr)
8.3 mmol) in CHCl3 (2 mL), and the reaction mixture was stirred
for 24 h. The reaction mixture was filtered and concentrated, and
the residue was purified by flash chromatography (3% acetone/
chloroform) to afford ketone 12 (40 mg, 67%) as an off-yellow
solid: 1H NMR (250 MHz, CDCl3) δ 7.05 (s, 1H), 3.95 (s, 3H),
2.54 (s, 3H), 2.01 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 191.7,
164.1, 163.3, 153.0, 109.7, 98.1, 56.7, 25.9, 9.4,; IR (KBr) νmax
3460, 2955, 2849, 1684, 1619, 1396, 1343, 1261, 1161 cm-1
;
HRMS (ESI) m/z calcd for C9H10O4Na 205.0477, found 205.0477.
6-(1-Iodoprop-1-en-2-yl)-4-methoxy-3-methyl-2H-pyran-2-
one (13). A solution of ketone 12 (40 mg, 0.22 mmol) and CHI3
(173 mg, 0.44 mmol) in dioxane (1 mL) were added by syringe to
a solution of anhydrous CrCl2 (162 mg, 1.32 mmol) in THF (1
mL) at 0 °C under argon. The reaction mixture was stirred at 0 °C
for 3 h, poured onto a large excess of water, and extracted with
Et2O. The combined organic extracts were washed with brine, dried
(MgSO4), and concentrated. The residue was purified by flash
chromatography (2% acetone/chloroform) to afford a 50:50 E/Z
mixture of vinyl iodide 13 (48 mg, 71%) as an off-white solid: 1H
NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 6.68 (s, 1H), 6.60 (dd, J
) 4.8, 2.4 Hz, 1H) 6.25 (s, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 2.18 (d,
J ) 2.4 Hz, 3H), 2.13 (d, J ) 1.6 Hz, 3H), 1.95 (s, 3H), 1.92 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 165.2, 164.0, 139.4, 136.9,
98.0, 97.5, 93.4, 89.9, 78.8, 56.4, 56.2, 23.2, 20.6, 8.8, 8.8; IR (KBr)
ν
max 3463, 3089, 2919, 1684, 1552, 1465, 1374, 1348, 1289, 1254
cm-1; HRMS (ESI) m/z calcd for C9H9IO3Na 314.9494, found
314.9496.
4-Methoxy-3-methyl-6-[(1E,3E,5E)-6-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)hexa-1,3,5-trienyl)-2H-pyran-2-one (10).
In a dry box, Pd2dba3 (1.2 mg, 1.3 µmol) and Ph3As (0.8 mg, 2.6
µmol) were added to a Schlenk flask equipped with a stir bar, which
was capped with a septum and removed from the dry box. A
solution of diene 4 (44 mg, 94 µmol) and vinyl iodide 3 (25 mg,
86 µmol) in N-methylpyrrolidone (NMP) (0.9 mL) was added by
syringe at 23 °C. The flask was wrapped with foil and stirred at 23
°C for 24 h. The reaction mixture was diluted with Et2O and poured
onto saturated aqueous NH4Cl. The aqueous layer was extracted
with Et2O, and the combined organic extracts were dried (MgSO4)
and concentrated. The residue was purified by flash chromatography
(2% acetone/chloroform) to afford 10 (26 mg, 88%) as an orange-
red solid: 1H NMR (400 MHz, CDCl3) δ 7.18 (dd, J ) 15.2, 10.8
Hz, 1H), 7.05 (dd, J ) 17.2, 10.4 Hz, 1H), 6.53 (dd, J ) 14.8,
10.4 Hz, 1H), 6.42 (dd, J ) 14.8, 10.2 Hz, 1H), 6.13 (d, J ) 15.2,
1H), 6.07 (s, 1H), 5.71 (d, J ) 17.6 Hz, 1H), 3.88 (s, 3H), 1.95 (s,
3H), 1.29 (s, 12H); 13C NMR (100 MHz, CDCl3) δ 165.2, 164.7,
157.0, 148.5, 139.3, 135.9, 134.1, 123.9, 117.0, 96.2, 83.4, 56.2,
24.8; IR (KBr) νmax 3425, 3143, 2990, 2896, 2249, 1813, 1790,
1649, 1561, 1472, 1378, 1096, 914, 750 cm-1; HRMS (ESI) m/z
calcd for C19H25BO5Na 367.1693, found 367.1692.
Gymnoconjugatin B (2). A reaction vessel was charged with
Pd(OAc)2 (1.7 mg, 7.6 µmol) and Ph3P (4.0 mg, 15 µmol) and
was flushed with argon. A solution of boronate 10 (26 mg, 70 µmol)
and vinyl bromide 5 (14 mg, 83 µmol) in THF (1 mL) was added
by syringe, followed by aqueous Na2CO3 (1 M, 0.15 mL, 0.15
mmol) in one portion. The flask was wrapped with foil and the
reaction mixture was stirred at 23 °C until thin-layer chromatog-
raphy (TLC) indicated the starting halide was consumed. The
reaction mixture was concentrated and the residue was purified by
preparative TLC (7% acetone/chloroform) to afford gymnoconju-
gatin B (18 mg, 77%) as a red solid: 1H NMR (400 MHz, DMSO-
d6) δ 7.68 (br s, 1H), 7.06 (dd, J ) 15.2, 11.5 Hz, 1H), 6.76 (dd,
J ) 15.6, 10.0 Hz, 1H), 6.74 (dd, J ) 15.1, 9.6 Hz, 1H), 6.67 (s,
1H), 6.59 (d, J ) 15.2 Hz, 1H), 6.59 (dd, J ) 14.6, 10.0 Hz, 1H),
6.55 (dd, J ) 14.6, 10.0 Hz, 1H), 6.54 (br s, 1H), 6.53 (br s, 1H),
6.51 (dd, J ) 14.6, 11.5 Hz, 1H), 6.36 (d, J ) 15.2 Hz, 1H), 3.89
(s, 3H), 1.81 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 165.9,
163.4, 156.9, 152.7, 143.5, 138.3, 135.6, 133.2, 131.6, 128.7, 127.2,
122.6, 121.3, 112.4, 110.1, 100.7, 96.8, 56.8, 8.9; UV (MeOH) λmax
442.5, 423.5, 330.5, 319.5, 264.0, 224.0 nm; IR (KBr) νmax 3154,
2990, 2896, 2249, 1813, 1790, 1649, 1561, 1467, 1384, 1167, 1091,
908, 744 cm-1; HRMS (ESI) m/z calcd for C19H18O4Na 333.1103,
found 333.1109.
ν
max 3472, 2943, 2907, 2849, 1713, 1666, 1631, 1543, 1455, 1384,
1349, 1243, 1149 cm-1; HRMS (ESI) m/z calcd for C9H9IO3Na
328.9651, found 328.9652.
4-Methoxy-3-methyl-6-[(6E)-7-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)hepta-2,4,6-trien-2-yl]-2H-pyran-2-one (14). In
a dry box, Pd2dba3 (1.6 mg, 2.0 µmol) and Ph3As (1.3 mg, 4.0
µmol) were added to a Schlenk flask equipped with a stir bar, which
was capped with a septum and removed from the dry box. A
solution of diene 4 (61 mg, 0.13 mmol) and vinyl iodide 13 (32
mg, 0.11 mmol) in NMP (1.5 mL) was added by syringe at 23 °C.
The flask was wrapped with foil and stirred at 23 °C for 24 h. The
reaction mixture was diluted with Et2O and poured onto saturated
aqueous NH4Cl. The aqueous layer was extracted with Et2O, and
the combined organic extracts were dried (MgSO4) and concen-
trated. The residue was purified by flash chromatography (2%
acetone/chloroform) to afford a 50:50 E/Z mixture of triene 14 (24
mg, 65%) as an orange-red solid: 1H NMR (400 MHz, CDCl3) δ
7.20 (d, J ) 2.4 Hz, 1H), 7.16 (s, 1H), 7.12-7.15 (m, 1H), 7.08-
7.10 (m, 1H), 6.69 (dd, J ) 14.8, 11.6 Hz, 1H), 6.58 (dd, J )
14.4, 10.4 Hz, 1H), 6.39 (dd, J ) 14.8, 10.8 Hz, 1H), 6.31 (d, J )
12 Hz, 1H), 6.20 (s, 1H), 6.15 (s, 1H), 5.71 (d, J ) 17.6 Hz, 1H),
5.64 (d, J ) 17.6 Hz, 1H), 3.91 (s, 3H), 3.89 (s, 3H), 2.07 (s, 3H),
2.00 (s, 3H), 1.28 (s, 12H), 1.27 (s, 12H); 13C NMR (100 MHz,
CDCl3) δ 165.6, 164.7, 159.3, 159.3, 149.4, 149.0, 139.4, 138.6,
134.2, 132.6, 131.3, 131.1, 128.4, 127.5, 103.1, 96.1, 93.1, 83.4,
83.3, 56.2, 56.1, 29.7, 27.8, 24.9, 24.8, 21.8, 17.5, 13.6, 12.6, 8.8,
8.7; IR (KBr) νmax 3425, 3143, 2990, 2896, 2249, 1631, 1531, 1384,
995 cm-1; HRMS (ESI) m/z calcd for C20H27BO5Na 381.1853,
found 381.1849.
Gymnoconjugatin A (1). A reaction vessel was charged with
Pd(OAc)2 (1.0 mg, 4.6 µmol) and Ph3P (2.4 mg, 9.2 µmol) and
was flushed with argon. A solution of boronate 14 (17 mg, 46 µmol)
and vinyl bromide 5 (8.8 mg, 51 µmol) in THF (1 mL) was added
by syringe, followed by aqueous Na2CO3 (1 M, 0.1 mL, 0.09 mmol)
in one portion. The flask was wrapped with foil and stirred at 23
°C until TLC indicated the starting halide was consumed. The
reaction mixture was concentrated and the residue was purified by
preparative TLC (7% acetone/chloroform) to afford a 50:50 E/Z
mixture of gymnoconjugatin A. This mixture was treated with a
catalytic amount of I2 in benzene (1 mL) at 25 °C. After 24 h, the
mixture was concentrated and purified by preparative TLC (7%
acetone/chloroform) to afford stereoisomerically pure gymnocon-
jugatin A (10 mg, 61%) as a red solid: 1H NMR (400 MHz,
DMSO-d6) δ 7.67 (br s, 1H), 7.05 (d, J ) 10.0 Hz, 1H), 6.72-
6-Acetyl-4-methoxy-3-methyl-2H-pyran-2-one (12). Selenium
dioxide (219 mg, 1.99 mmol) was added in a single portion to a
solution of pyrone 11 (51 mg, 0.33 mmol) in dioxane (1.3 mL) in
a sealed tube. The reaction mixture was warmed at 190 °C and
was stirred rapidly at this temperature for 3 h. The reaction mixture
was cooled to room temperature and filtered, and the filtrate was
concentrated. The crude product was treated with MnO2 (720 mg,
J. Org. Chem, Vol. 71, No. 26, 2006 9843