S. Anderson et al.
FULL PAPER
10À5 mol), triphenylphosphine (36 mg, 1.4î10À4 mol), triethylamine
(20 mL, freshly distilled over CaH2), phenylacetylene (384 mg, 413 mL,
3.8î10À3 mol). For the TIPS deprotection: dichloromethane (100 mL),
TBAF (1m in THF, 3.42 mL, 3.42î10À3 mol). The crude reaction mixture
was chromatographed (silica, CH2Cl2/hexanes 1:1) to yield 7c as a thick
12: See the preparation of 5b for the general procedure. Quantities used:
acetic acid 2-iodo-5-methylphenyl ester (10 g, 2.58î10À2 mol), palladi-
um(ii) acetate (116 mg, 5.2î10À4 mol), copper(i) iodide (50 mg, 2.6î
10À4 mol), triphenylphosphine (262 mg, 1.0î10À3 mol), triethylamine
(60 mL), and triisopropylsilylacetylene (4.7 g, 5.78 mL, 2.58î10À2 mol).
Chromatography (silica, 5% ethyl acetate/hexanes) yielded 12 as a white
solid (5 g, 44%). 1H NMR (300 MHz, CDCl3): d = 8.2 (d, 3J(H,H) =
8 Hz, 1H), 7.18 (d, 4J(H,H) = 2 Hz, 1H), 7.06 (dd, 3J(H,H) = 8 Hz,
4J(H,H) = 2 Hz, 1H) 1.12 ppm (s, 21H); MS (GC EIMS): m/z: 442
[M]+, 399 [MÀAc]+.
1
colorless oil (1.25 g, 91%). H NMR (300 MHz, CDCl3): d = 7.6 7.4 (m,
3
3H), 7.4 7.3 (m, 4H), 3.06 (s, 1H), 2.56 (t, J(H,H) = 7.6 Hz, 2H), 1.65
1.5 (m, 2H), 1.49 (s, 9H), 1.2 1.4 (m, 6H), 0.89 ppm (t, J = 7 Hz, 3H);
13C NMR (75 MHz, CDCl3): d = 151.17, 150.54, 136.29, 134.45, 134.28,
132.10, 129.05, 128.71, 123.20, 120.30, 118.64, 95.02, 84.22, 83.96, 82.80,
77.78, 32.00, 30.44, 30.05, 29.43, 27.99, 22.93, 14.49 ppm; MS (CIMS): m/
z: 420 [M+NH4]+, 320 [M+NH4ÀtBOC]+.
13: See the preparation of 6b for experimental details. Quantities used
for acetate deprotection: NaOH (0.45 g, 1.1î10À2 mol, in methanol
2 mL), 12 (5 g, 1.1î10À2 mol, in THF 75 mL). Quantities used for t-butyl
carbonate formation: THF (65 mL), potassium carbonate (2.45 g, 1.8î
10À2 mol), DMAP (catalytic amount), 18-crown-6 (catalytic amount), di-
tert-butyl dicarbonate (2.84 g, 1.3î10À2 mol). Chromatography (silica,
CH2Cl2/hexanes 1:3) gave a waxy solid that was recrystallized from pen-
8c: See the preparation of 8b for experimental details. Quantities used:
6c (1.82 g, 3.1î10À3 mol), arylacetylene 7c (1.25 g, 3.1î10À3 mol), palla-
dium(ii) acetate (13.9 mg, 6.2î10À5 mol), copper(i) iodide (6 mg, 3.1î
10À5 mol), triphenylphosphine (33 mg, 1.2î10À4 mol), triethylamine
(20 mL, freshly distilled over CaH2). For the TIPS deprotection: CH2Cl2
(125 mL) and TBAF (3.1 mL, 1m in THF, 3.1î10À3 mol). Chromatogra-
phy of the crude reaction mixture (silica, CH2Cl2/hexanes 1:1) yielded 8c
as a pale yellow viscous oil (1.96 g, 90%). 1H NMR (300 MHz, CDCl3): d
= 7.60 7.55 (m, 1H), 7.55 7.45 (m, 3H), 7.40 7.30 (m, 5H), 3.06 (s, 1H),
2.50 2.64 (m, 4H), 1.65 1.45 (m, 4H), 1.40 1.25 (m, 12H), 0.95 0.80 ppm
(m, 6H); 13C NMR (75 MHz, CDCl3): d = 151.19, 151.14, 150.58, 150.40,
136.37, 136.29, 134.46, 134.39, 134.10, 133.72, 132.09, 129.05, 128.73,
123.23, 120.97, 120.35, 118.66, 118.39, 95.01, 93.79, 84.35, 84.23, 84.18,
83.99, 82.74, 77.63, 32.03, 32.00, 30.51, 30.44, 30.11, 30.05, 29.46, 29.43,
28.03, 28.00, 22.93*, 14.52* ppm.
1
tane to yield 13 (5.36 g, 95%). H NMR (300 MHz, CDCl3): d = 7.75 (d,
3J(H,H) = 8 Hz, 1H), 7.26 (d, 4J(H,H) = 2 Hz, 1H), 7.07 (dd, 3J(H,H)
4
= 8 Hz, J(H,H) = 2 Hz, 1H), 1.59 (s, 9H), 1.12 ppm (s, 21H); MS (ES+
MS): m/z: 523 [M+Na]+, 539 [M+K]+, 555 [M+Na+MeOH]+.
14: See the preparation of 7b for experimental details. Quantities used
for the coupling reaction: 13 (2.5 g, 5.0î10À3 mol), palladium(ii) acetate
(22.2 mg, 1.0î10À4 mol), copper(i) iodide (9.5 mg, 5.0î10À5 mol), triphe-
nylphosphine (53 mg, 2.0î10À4 mol), triethylamine (25 mL), phenylacety-
lene (572 mg, 615 mL, 5.6î10À3 mol). The product was chromatographed
(silica, CH2Cl2/hexanes 1:3). TIPS deprotection: CH2Cl2 (100 mL) TBAF
(1m in THF, 4.7 mL, 4.7î10À3 mol). Chromatography (silica, CH2Cl2/hex-
anes 2:1) followed by recrystallization from pentane yielded 14 as a pale
yellow waxy solid (1.4 g, 94%). 1H NMR (300 MHz, CDCl3): d = 7.56
9c: See the preparation of 9b for experimental details. Carbonic acid
tert-butyl ester 2-iodophenyl ester (0.89 g, 2.8î10À3 mol), 8c (2.0 g, 2.8î
10À3 mol), palladium(ii) acetate (12.5 mg, 5.6î10À5 mol), copper(i) iodide
(5.3 mg, 2.8î10À5 mol), triphenylphosphine (29.3 mg, 1.1î10À4 mol) tri-
ethylamine (16 mL, freshly distilled over CaH2). The crude reaction mix-
ture was chromatographed (silica, CH2Cl2/hexanes 1:1) to yield 9c as a
4
7.49 (m, 3H), 7.39 7.33 (m, 4H), 7.32 (d, J(H,H) = 2, 1H), 3.20 (s, 1H),
1.52 ppm (s, 9H); 13C NMR (75 MHz, CDCl3): d
= 151.52, 151.22,
133.00, 131.91, 129.90, 129.00, 128.56, 125.87, 123.44, 122.89, 118.69, 96.49,
1
white foam (2.3 g, 92%). H NMR (300 MHz, CDCl3): d = 7.60 7.45 (m,
84.30, 83.81, 82.52, 79.85, 27.84 ppm; MS (ES+ MS): m/z: 341 [M+Na]+.
5H), 7.40 7.30 (m, 6H), 7.30 7.15 (m, 2H), 2.58 (m, 4H), 1.70 1.45 (m,
4H), 1.56 (s, 9H), 1.52 (s, 9H), 1.50 (s, 9H), 1.45 1.25 (m, 12H), 0.85
15: See the preparation of 8b for experimental details. Quantities used:
14 (2.2 g, 4.4î10À3 mol), 13 (1.4 g, 4.4î10À3 mol), palladium(ii) acetate
(19.1 mg, 9.0î10À5 mol), copper(i) iodide (8.3 mg, 4.3î10À5 mol), triphe-
nylphosphine (45 mg, 1.7î10À4 mol), triethylamine (25 mL). Chromatog-
raphy (silica, CH2Cl2/hexanes 1:2) yielded the TIPS-protected acetylene.
TIPS deprotection: CH2Cl2 (100 mL) and TBAF (1m in THF, 3.54 mL,
3.54î10À3 mol). Chromatography (silica, CH2Cl2/hexanes 1:1) followed
by recrystallization from pentane yielded 15 as a waxy solid (1.9 g, 80%).
1H NMR (300 MHz, CDCl3): d = 7.64 7.57 (m, 4H), 7.41 7.32 (m, 7H),
0.95 ppm (m, 6H); 13C NMR (75 MHz, CDCl3): d
= 152.14, 151.78,
151.19, 151.16, 150.39, 150.37, 136.33, 136.30, 134.06, 134.03, 133.86,
133.71, 133.37, 132.09, 131.98, 130.09, 129.05, 128.73, 126.42, 123.24,
122.51, 121.25, 121.02, 118.68, 118.39, 117.78, 95.01, 93.73, 93.69, 84.69,
84.30*, 84.25, 84.22, 84.01, 32.03*, 30.51*, 30.11, 30.10, 29.46, 28.11, 28.05,
28.00, 22.92*, 14.50* ppm; MS (APCI): m/z: 794 [MÀtBOC]+, 695
[MÀ2tBOC]+, 595 [MÀ3tBOC]+.
1c: See the preparation of 1b for experimental details. Quantities used:
9c (1.35 g, 1.51î10À3 mol). For the cyclization: methanol (50 mL) and
NaOH (0.23 g, 1.51î10À3 mol). Yield of 1c (0.52 g, 60%); m.p. 1078C;
1H NMR (300 MHz, CDCl3): d = 7.96 7.89 (m, 4H), 7.62 7.46 (m, 6H),
7.39 (tt, 1H), 7.31 7.21 (m, 2H), 7.10 (s, 1H), 7.04 (s, 1H), 7.01 (s, 1H),
3.05 (m, 4H), 1.89 (m, 4H), 1.54 1.37 (m, 12H), 0.95 0.89 ppm (m, 6H);
13C NMR (75 MHz, CDCl3): d = 157.64, 157.31, 156.83, 155.20, 154.37,
154.24, 130.79, 130.04, 129.96, 129.76, 129.24, 129.11, 127.30, 127.10,
126.15, 126.09, 125.35, 124.17, 123.22, 122.20, 121.80, 121.03, 115.57,
115.33, 111.44, 102.08, 101.11, 100.64, 32.11, 32.10, 30.37, 30.34, 30.21*,
29.62*, 23.05*, 14.58, 14.55 ppm; MS (MALDIMS): m/z: 594 [M]+ ; ele-
mental analysis calcd (%) for C42H42O3 (594.84): C 84.80, H 7.13; found:
C 84.32, H 7.28; lmaxabs[loge]=309[4.88], 334[4.69],348[4.59] nm; lmaxPL
362, 378 nm; FPL 0.93.
3.22 (s, 1H), 1.53 ppm (s, 18H); 13C NMR (75 MHz, CDCl3): d
=
151.66*, 151.64, 151.20, 133.06, 133.00, 131.92, 129.95, 129.37, 129.03,
128.59, 125.95, 125.43, 123.95, 123.94, 122.92, 118.55, 118.14, 96.72, 95.11,
86.29, 84.50, 84.28, 83.95, 82.45, 80.14, 27.85* ppm; MS (ES+ MS): m/z:
557 [M+Na]+.
16: See the preparation of 9b for experimental details. Quantities used:
Carbonic acid tert-butyl ester 2-iodophenyl ester (1.25 g, 3.91î10À3 mol),
15 (1.9 g, 3.55î10À3 mol), palladium(ii) acetate (17.8 mg, 8.0î10À5 mol),
copper(i) iodide (7.6 mg, 4î10À5 mol), triphenylphosphine (42 mg, 1.6î
10À4 mol), triethylamine (10 mL), pyridine (10 mL, freshly distilled over
CaH2). The reaction mixture was stirred at 708C overnight. Chromatog-
raphy (silica, CH2Cl2/hexanes 3:1) gave a mixture of the product and a
significant impurity which could be removed by repeated recrystallization
from chloroform/hexane. 16 was obtained as
a bright yellow solid
11: Acetyl chloride (2.7 g, 2.5 mL, 3.5î10À2 mol) was added dropwise to
a solution of triethylamine (3.5 g, 4.8 mL, 3.5î10À2 mol), 10[21] (10 g,
2.9î10À2 mol) and dimethylaminopryridine (234 mg, 2.08î10À3 mol) in
CH2Cl2 (220 mL) at 08C. The mixture was stirred for 1 h, and then
washed with aqueous ammonium chloride (500 mL, 10% solution) and
aqueous sodium bicarbonate (500 mL, 5% solution). The organic layer
was dried (MgSO4) and evaporated. The crude product was chromato-
graphed (silica, hexane containing 5% ethyl acetate) and then recrystal-
lised from a minimum volume of hot hexane to yield 11 (10.9 g, 97%).
(750 mg, 30%). 1H NMR (300 MHz, CDCl3): d = 7.60 7.50 (m, 5H),
7.45 7.34 (m, 8H), 7.24 7.18 (m, 2H), 1.52 ppm (s, 27H); 13C NMR
(75 MHz, CDCl3): d = 151.99, 151.74, 151.63, 151.52, 151.17*, 133.20,
133.04, 132.97, 131.90, 130.22, 129.35*, 129.01, 128.57, 126.25, 125.42,
125.39, 124.80, 123.99, 122.89, 122.34, 118.49, 117.66, 117.27, 96.70, 95.13,
93.28, 87.04, 86.49, 84.40, 84.26, 84.14, 83.95, 27.86, 27.83* ppm; MS (ES+
MS): m/z: 749 [M+Na]+.
2: Compound 16 (250 mg, 3.44î10À4 mol) was heated to 1808C under re-
duced pressure (0.02 mbar) until no further evolution of gas was ob-
served. The resultant yellow glass was dissolved in methanol (35 mL)
containing NaOH (0.042 g, 1.03î10À3 mol), the resultant mixture was re-
fluxed overnight to produce a precipitate that was collected by centrifu-
gation. It was then washed with methanol (3î50 mL). The yellow solid
3
1H NMR (300 MHz, CDCl3): d = 7.52 (d, J(H,H) = 8 Hz, 1H), 7.43 (d,
4J(H,H)
= =
2 Hz, 1H), 7.30 (dd, 4J(H,H) 2, 3J(H,H) 8 Hz, 1H) ,
2.36 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d
= 168.66, 152.11,
140.87, 137.17, 132.50, 93.61, 90.76, 21.56 ppm; MS (GC EIMS): m/z: 388
[M]+, 345 [MÀAc]+.
526
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2004, 10, 518 527