Z. Ahmed, U. Albrecht, P. Langer
FULL PAPER
(EI, 70 eV): m/z (%) = 251.8 (18) [M+], 219.7 (12), 178.8 (21), 147.3
(78), 120.9 (23), 90.8 (33). C13H16O5 (252.26): calcd. C 61.89, H
6.39; found: C 61.93, H 6.50.
was isolated by rapid chromatography (silica gel, dichloromethane)
of the reaction mixture as a yellow solid (522 mg, 73%, E:Z = 2:1),
1
m.p.112–114 °C. H NMR (300 MHz, CDCl3): δ = 3.80, 3.82 (s, 3
H, OCH3, E/Z isomers), 3.81, 3.83 (s, 3 H, OCH3, E/Z isomers),
3.94, 4.29 (s, 3 H, OCH3, E/Z isomers), 6.89–7.03 (m, 2 H, ArH),
7.19–7.45 (m, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ =
52.70, 52.84, 55.65, 55.85, 60.21, 60.91 (CH3), 110.60, 111.45 (CH),
114.89, 115.62, 118.19, 119.03 (C), 118.31 (q, 2 CF3, J = 319.5 Hz),
119.87, 119.96 (C), 120.13, 120.87, 131.05, 131.67 (2 C), 131.93
(CH), 139.44, 141.47, 155.45, 156.45, 157.22, 157.44, 159.51,
Synthesis of Silyl Enol Ether 4: The reaction was carried out analo-
gous to a known procedure.[11b,12] To a stirred benzene solution
(10 mL) of
3 (6.90 g, 27.35 mmol) was added triethylamine
(6.10 mL, 43.76 mmol). After stirring for 2 h, chlorotrimethylsilane
(6.21 mL, 49.23 mmol) was added. After stirring for 72 h, the sol-
vent was removed in vacuo and to the residue was added hexane
(100 mL) to give a suspension. The latter was filtered under Argon.
The filtrate was distilled in vacuo to give 4 as a yellow oil (8.44 g,
159.93, 164.75, 165.75 (C) ppm. IR (KBr): ν = 1799 cm–1 (s), 1720
˜
(s), 1659 (s), 1425 (s), 1325 (m), 1280 (m), 1226 (s), 1129 (s), 1086
(s), 810 (m), 759 (m) cm–1. MS (EI, 70 eV): m/z (%) = 438.7 (23)
[M+], 249.0 (53), 221.0 (100), 91.0 (51). C16H13O9SF3 (437.74):
calcd. C 43.90, H 2.99; found: C 44.06, H 3.12.
1
95%). H NMR (300 MHz, CDCl3): δ = –0.14, 0.21 (s, 9 H, CH3,
E/Z isomers), 3.11, 3.32, (s, 3 H, OCH3, E/Z isomers), 3.53, 3.56
(s, 3 H, OCH3, E/Z isomers), 3.67, 3.69 (s, 3 H, OCH3, E/Z iso-
mers), 3.63, 4.45 (s, 2 H, OCH2, E/Z isomers), 6.76–6.86 (m, 2 H,
ArH, E/Z isomers), 7.05–7.20 (m, 2 H, ArH, E/Z isomers) ppm.
Synthesis of Butenolides 8a: A dioxane solution (5 mL per 1 mmol
of triflate) of triflate 7 (438 mg, 1.00 mmol), phenylboronic acid
(158 mg, 1.30 mmol), K3PO4 (340 mg, 1.60 mmol) and [Pd(PPh3)4]
(35 mg, 0.03 mmol) was refluxed for four hours. A saturated aque-
ous solution of ammonium chloride was added. The organic and
the aqueous layer were separated and the latter was extracted (3 ×)
with ether. The combined organic layers were dried (Na2SO4), fil-
tered and the filtrate was concentrated in vacuo. The residue was
purified by chromatography (silica gel, EtOAc/hexane) to give 8a
Synthesis of 1,3-Bis(silyl enol ether) 5: The reaction was carried out
analogous to a known procedure.[11b,12] To a stirred THF solution
(100 mL) of LDA (39.01 mmol, 1.5 equiv.) was added 4 (8.44 g,
26.01 mmol) at –78 °C. After stirring for 1 h, chlorotrimethylsilane
(6.00 mL, 46.82 mmol) was added. The solution was warmed to
room temperature during 12 h with stirring. The solvent was re-
moved in vacuo and to the residue was added hexane (100 mL) to
give a suspension. The latter was filtered under Argon. The filtrate
1
as a yellow solid (335 mg, 92%, E:Z = 2:1), m.p. 168–169 °C. H
1
was distilled in vacuo to give 5 as a yellow oil (10.00 g, 97%). H
NMR (300 MHz, CDCl3): δ = 3.32, 3.78 (s, 3 H, OCH3, E/Z iso-
mers), 3.81, 3.82 (s, 3 H, OCH3, E/Z isomers), 3.83, 3.85 (s, 3 H,
OCH3, E/Z isomers), 6.90–7.03 (m, 2 H, ArH, E/Z isomers), 7.25–
7.51 (m, 7 H, ArH, E/Z isomers) ppm. 13C NMR (75 MHz,
CDCl3): δ = 52.52, 52.63, 55.67, 55.88, 60.49, 61.19 (CH3), 109.05,
111.23 (C), 110.49, 111.38 (CH), 113.50, 114.34 (C), 120.02, 120.87
(CH), 121.07, 121.49 (C), 128.32 (4 C), 128.36 (2 C, CH), 128.51,
130.91 (C), 128.88, 128.99, 129.66, 129.94 (2 C), 130.41, 132.10,
132.21 (CH), 143.83, 145.90, 157.24, 157.66, 162.48, 163.45, 165.81,
NMR (300 MHz, CDCl3): δ = 0.02, 0.03 (s, 9 H, CH3, E/Z iso-
mers), 0.29, 0.31 (s, 9 H, CH3, E/Z isomers), 3.38, 3.41 (s, 3 H,
OCH3, E/Z isomers), 3.45, 3.51 (s, 3 H, OCH3, E/Z isomers), 3.78,
3.79 (s, 3 H, OCH3, E/Z isomers), 5.67, 5.81 (s, 1 H, OCH, E/Z
isomers), 6.84–6.89 (m, 2 H, ArH, E/Z isomers), 7.13–7.19 (m, 2
H, ArH, E/Z isomers) ppm.
Synthesis of the Butenolide 6: The reaction was carried out analo-
gous to a known procedure.[11b,12] To a CH2Cl2 solution (120 mL)
167.00, 167.05, 167.61 (C) ppm. IR (KBr): ν = 3511 cm–1 (w), 3465
of oxalyl chloride (1.06 mL, 12.01 mmol) and of
5 (3.66 g,
˜
9.24 mmol) was added a CH2Cl2 solution (5 mL) of Me3SiOTf
(1.01 mL, 5.54 mmol) at –78 °C. The temperature of the reaction
mixture was rised to 20 °C during 12 h. After stirring for 2 h at
20 °C, a saturated aqueous solution of NaCl was added. The aque-
ous layer was separated and extracted with CH2Cl2. The combined
organic layers were washed with an aqueous solution of HCl
(10%), dried (Na2SO4) and filtered. The solvent of the filtrate was
removed in vacuo and the residue was purified by column
chromatography (silica gel, hexane/EtOAc) to give 6 as a yellow
solid (1.78 g, 63%, E:Z = 2:1), m.p. 136–137 °C. 1H NMR
(300 MHz, CDCl3): δ = 3.70, 3.73 (s, 3 H, OCH3, E/Z isomers),
3.72, 3.74 (s, 3 H, OCH3, E/Z isomers), 3.76, 4.11 (s, 3 H, OCH3,
E/Z isomers), 6.79–6.93 (m, 2 H, ArH), 7.09–7.33 (m, 2 H, ArH)
ppm. 13C NMR (150 MHz, (CD3)2DO): δ = 52.32, 52.41, 56.07,
56.25, 59.48, 60.14 (CH3), 111.47, 112.51 (CH), 112.55, 113.52 (C),
120.50, 121.27 (CH), 122.83, 122.87, 126.68, 127.65 (C), 130.85,
131.28, 133.16, 133.39 (CH), 143.67, 144.16, 144.30, 146.30, 158.39,
(w), 2975 (m), 2949 (m), 1771 (s), 1722 (s), 1628 (s), 1598 (s), 1492
(m), 1438 (m), 1245 (m), 1224 (m), 755 (m), 724 (m) cm–1. MS (EI,
70 eV): m/z (%) = 366.7 (100) [M+], 251.5 (25), 219.3 (31), 144.9
(10), 89.1 (39). C21H18O6 (366.37): calcd. C 68.84, H 4.95; found:
C 68.34, H 5.15.
Synthesis of 8b: The synthesis was carried out according to the
procedure given for 8a. Starting with triflate
7 (300 mg,
0.68 mmol), p-tolylboronic acid (121 mg, 0.89 mmol), K3PO4
(232 mg, 1.09 mmol), [Pd(PPh3)4] (24 mg, 0.02 mmol) and dioxane
(3.5 mL), 8b was isolated as a yellow solid (222 mg, 85%, E:Z =
1
2:1), m.p. 140 °C. H NMR (300 MHz, CDCl3): δ = 2.35, 2.38 (s,
3 H, CH3, E/Z isomer), 3.31, 3.78 (s, 3 H, OCH3, E/Z isomers),
3.81, 3.82 (s, 3 H, OCH3, E/Z isomers), 3.83, 3.84 (s, 3 H, OCH3,
E/Z isomers), 6.89, 7.55 (m, 8 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.31 (2 C, CH3), 52.50, 52.59, 55.63, 55.84, 60.33,
61.02 (CH3), 109.19, 111.47 (C), 110.43, 111.32 (CH), 113.18,
114.04 (C), 119.97, 120.82 (CH), 121.07, 121.48, 125.35, 125.43,
126.72, 129.36 (C), 129.04 (2 C), 129.07 (2 C), 129.44 (2 C), 129.74
(2 C), 130.36, 130.83, 132.12, 132.22 (CH), 138.97, 139.14, 143.93,
146.02, 157.19, 157.62, 162.14, 163.00, 167.10, 167.75 (C) ppm. IR
158.95, 164.58, 164.82, 166.10, 167.50 (C) ppm. IR (KBr): ν =
˜
3321 cm–1 (m), 1789 (s), 1764 (s), 1718 (s), 1676 (s), 1369 (m), 1322
(m), 1278 (m), 1248 (m), 1148 (m), 1106 (m) cm–1. MS (EI, 70 eV):
m/z (%) = 306.0 (7) [M+], 203.9 (15), 180.0 (29), 147.4 (39), 91.0
(44). C15H14O7 (306.27): calcd. C 58.82, H 4.60; found: C 58.79, H
4.27.
(KBr): ν = 2948 cm–1 (w), 1768 (s), 1721 (s), 1621 (s), 1490 (m),
˜
1458 (m), 1275 (s), 1249 (s), 1039 (m), 933 (m) cm–1. MS (EI, 70 eV)
= m/z (%): 380.1 (2) [M+], 309.1 (2), 182.0 (15), 32.0 (26), 28.0
(100). C22H20O6 (380.40): calcd. C 69.46, H 5.29; found: C 69.31,
H 5.67.
Preparation of Triflate 7: The reaction was carried out analogous
to a known procedure.[11b,12] To a dichloromethane solution
(16 mL) of 6 (500 mg, 1.63 mmol) and triflic anhydride (0.30 mL,
1.79 mmol) was added pyridine (0.26 mL, 3.26 mmol) at –78 °C.
The solution was warmed to –10 °C within 4 hours. The product
Synthesis of Calycine (E-9a) and Isocalycine (Z-9a): To a CH2Cl2
(5 mL) solution of 8a (90 mg, 0.24 mmol) was added BBr3
3472
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 3469–3474