M. W. Göbel et al.
FULL PAPER
(m, 1 H, aryl-H), 8.22 (d, J = 7.8 Hz, 1 H, aryl-H), 7.97 (m, 1 ing in vacuo, a yellow solid (230 mg, 30%) was obtained. Rf = 0.15
H, aryl-H), 7.88 (s, 1 H, aryl-H), 7.75–7.63 (m, 5 H, aryl-H, NH, (n-hexane/EtOAc, 10:1). M.p. 86–87 °C. 1H NMR (250 MHz, [D6]-
exchangeable with D2O), 7.42–7.33 (m, 6 H, C6H5, aryl-CH), 6.34 DMSO): δ = 7.85 (t, J = 6.5 Hz, 2 H, aryl-H), 7.57 (s + d, J =
(dd, J = 15.8, J = 6 Hz, 1 H, aryl-CH=CH), 5.11 (s, 2 H, Ph-CH2),
4.47 (m, 1 H, NCH), 3.73 (m, 2 H, CH2-OTBS), 0.87 [s, 9 H,
9.3 Hz, 2 H, aryl-H), 7.44–7.27 (m, 9 H, aryl-H, NH), 6.61 (d, J =
16 Hz, 1 H, aryl-CH), 6.26 (dd, J = 16, J = 6.25 Hz, 1 H, aryl-
(CH3)3], 0.06 [s, 6 H, (CH3)2] ppm. 13C NMR (62.9 MHz, [D6]- CH=CH), 5.05 (s, 2 H, Ph-CH2), 4.28 (m, 1 H, NCH), 3.91 (s, 2
DMSO): δ = 155.7, 137.1, 133.1, 131.5, 131.2, 129.8, 129.7, 129.4,
H, fluorenyl-9H), 3.63 (m, 2 H, CH2-OTBS), 0.86 [s, 9 H, (CH3)3],
128.4, 128.2, 127.7, 126.9, 126.7, 126.6, 124.5, 123.9, 123.2, 122.6,
0.04 [s, 6 H, (CH ) ] ppm. IR (KBr): ν = 3428 (w), 3290 (m), 3034
˜
3 2
65.3, 65.1, 54.8, 25.6, 17.8, –5.4 ppm. IR (KBr): ν = 3305 (m), 3063
(w), 2953 (m), 2858 (m), 1690 (s), 1541 (s), 1460 (w), 1288 (m),
(w), 2929 (m), 2857 (m), 1711 (s), 1691 (s), 1542 (m), 1459 (m),
˜
1252 (m), 1083 (m), 969 (m), 838 (m), 738 (m) cm–1. C31H37NO3Si
1250 (m), 1120 (m), 1052 (m), 964 (w), 842 (m), 776 (m), 745 (m), (499.72): C 74.51, H 7.46, N 2.80; found C 74.58, H 7.52, N 3.03.
695 (w) cm–1. C32H37NO3Si (511.73): C 75.11, H 7.29, N 2.74; [α]2D0 = –2.7 (c = 0.9, MeOH).
found C 74.89, H 7.35, N 2.58. [α]2D0 = +29.2 (c = 1.0, MeOH).
General Procedure for the Synthesis of the Fmoc-Protected Amino
Benzyl (S)-[1-(tert-Butyldimethylsilyloxymethyl)-3-(quinolin-3-yl)- Alcohols 5a and 5c–e: The Heck coupling product 4a,c–e (1 equiv.)
allyl]carbamate (4d): The residue was purified by column
chromatography (n-hexane/EtOAc, 10:1, then 3:1). A colourless oil
(552 mg, 80%) was furnished after drying in vacuo. Rf = 0.45 (n-
hexane/EtOAc, 2:1). 1H NMR (250 MHz, [D6]DMSO): δ = 9.00
(d, J = 2.3 Hz, 1 H, aryl-H), 8.29 (s, 1 H, aryl-H), 7.97 (m, 2 H,
aryl-H), 7.72 (m, 1 H, aryl-H), 7.60 (m, 1 H, aryl-H), 7.50 (d, J =
8.3 Hz, 1 H, NH, exchangeable with D2O), 7.37–7.31 (m, 5 H,
was dissolved in EtOH (20 mL). 1,4-Cyclohexadiene (15 equiv.)
and Pd(OH)2 (0.3 equiv.) were added. The reaction mixture was
refluxed for 16 h. After quantitative conversion, the mixture was
filtered through Celite® and concentrated in vacuo. The crude
product was dissolved in 1 TBAF in THF (2.4 equiv.) and stirred
at room temperature for at least 5 h. The reaction was quenched
with saturated NaHCO3 and the mixture extracted three times with
C6H5), 6.74 (d, J = 16.3 Hz, 1 H, aryl-CH=CH), 6.54 (dd, J = 16.3, EtOAc. The combined organic layers were dried with MgSO4 and
J = 5.8 Hz, 1 H, aryl-CH=CH), 5.07 (s, 2 H, Ph-CH2), 4.35 (m, 1
H, NCH), 3.67 (m, 2 H, CH2-OTBS), 0.85 [s, 9 H, (CH3)3], 0.05 [s,
6 H, (CH3)2] ppm. 13C NMR (100.6 MHz, [D6]DMSO): δ = 155.8,
149.0, 146.8, 137.1, 132.0, 130.6, 129.5, 129.2, 128.6, 128.3, 128.1,
127.7, 127.6, 127.2, 127.0, 126.3, 65.3, 64.8, 54.9, 25.7, 17.9,
the solvents evaporated in vacuo. The residue was dissolved in
EtOAc/EtOH (2:1, 30 mL) before Fmoc-OSu (1.1 equiv.) was
added. Then the reaction mixture was stirred at room temp. for
1 h. The precipitate was filtered, washed with ice-cold EtOAc and
dried in vacuo.
–5.4 ppm. IR (film): ν = 3440 (m), 3324 (m), 3033 (m), 2953 (s),
˜
(9H-Fluoren-9-yl)methyl (S)-[1-(Hydroxymethyl)-3-(pyren-1-yl)pro-
pyl]carbamate (5a): Carbamate 4a (500 mg, 0.93 mmol) was used
as the starting material in this reaction. After recrystallisation from
MeCN, a colourless solid (280 mg, 59%) was obtained. Rf = 0.35
(n-hexane/EtOAc, 1:1). M.p. 158–160 °C. 1H NMR (250 MHz,
[D6]DMSO): δ = 8.43–7.77 (m, 13 H, aryl-H), 7.44–7.30 (m, 5 H,
aryl-H, NH, exchangeable with D2O), 4.70 (t, J = 5.5 Hz, 1 H, OH,
exchangeable with D2O), 4.45–4.25 (m, 3 H, COOCH2-CH), 3.62
2856 (s), 1718 (s), 1495 (s), 1470 (m), 1375 (w), 1253 (s), 1112 (s),
968 (m), 909 (w), 837 (m), 780 (m), 697 (m) cm–1. C27H34N2O3Si
(462.66): C 70.09, H 7.41, N 6.05; found C 69.94, H 7.44, N 6.17.
[α]2D0 = +29.1 (c = 0.8, MeOH).
Benzyl (S)-[3-(Anthracen-9-yl)-1-(tert-butyldimethylsilyloxymethyl)-
allyl]carbamate (4e): The residue was purified by column
chromatography (n-hexane/EtOAc, 25:1). After recrystallisation
from MeCN, a light yellow solid (590 mg, 77%) was obtained. Rf (m, 1 H, NCH), 3.49–3.17 (m, 4 H, CH2OH, aryl-CH2), 2.02 (m,
= 0.2 (n-hexane/EtOAc, 10:1). M.p. 68–70 °C. 1H NMR (250 MHz, 1 H, aryl-CH2-CHa), 1.85 (m, 1 H, aryl-CH2-CHb) ppm. 13C NMR
[D6]DMSO): δ = 8.54 (s, 1 H, aryl-H), 8.29 (d, J = 7.8 Hz, 2 H,
aryl-H), 8.09 (dd, J = 7.3, J = 2 Hz, 2 H, aryl-H), 7.70 (d, J =
7.5 Hz, 1 H, NH, exchangeable with D2O), 7.56–7.28 (m, 10 H,
C6H5, aryl-CH, aryl-H), 5.97 (dd, J = 16.3, J = 6 Hz, 1 H, aryl-
(75.4 MHz, [D6]DMSO): δ = 157.1, 142.4, 139.3, 137.3, 137.0,
130.8, 130.3, 129.1, 128.8, 127.9, 127.34, 127.26, 127.2, 127.0,
126.3, 126.0, 124.85, 124.78, 124.6, 124.1, 124.0, 123.5, 121.3,
119.9, 109.6, 65.5, 52.5, 35.1, 29.1 ppm. IR (KBr): ν = 3446 (m),
˜
CH=CH), 5.12 (s, 2 H, Ph-CH2), 4.54 (m, 1 H, NCH), 3.80 (m, 2 3304 (s), 3037 (m), 2946 (m), 2870 (w), 1685 (s), 1546 (s), 1449 (m),
H, CH2-OTBS), 0.89 [s, 9 H, (CH3)3], 0.10 [s, 6 H, (CH3)2] ppm.
1354 (w), 1294 (m), 1267 (m), 1142 (w), 1056 (m), 842 (m), 738
13C NMR (75.4 MHz, [D6]DMSO): δ = 155.8, 137.1, 136.4, 132.1,
(m), 624 (w) cm–1. C35H29NO3 (511.61): C 82.17, H 5.71, N 2.74;
130.8, 128.7, 128.4, 128.3, 127.70, 127.67, 126.1, 125.9, 125.6, found C 81.97, H 5.95, N 2.97. [α]2D0 = +30.1 (c = 1.0, DMF).
125.4, 125.2, 65.3, 64.9, 55.1, 25.7, 17.9, –5.4 ppm. IR (KBr): ν =
˜
(S)-2-[(9H-Fluoren-9-yl)methoxycarbonylamino]-4-(pyren-1-yl)-
butyric Acid (6a): The Fmoc-protected amino alcohol 5a (330 mg,
0.64 mmol) was dissolved in DMF (20 mL), and PDC (1.45 g,
3.87 mmol) was added to the clear solution. The mixture was
stirred at room temp. overnight. For workup, the reaction was
quenched with brine and the mixture extracted three times with
EtOAc. The combined organic layers were washed with saturated
aqueous Na2S2O5 solution and concentrated in vacuo. The crude
product was adsorbed on silica gel and purified by column
chromatography (EtOAc to EtOAc/MeOH, 9:1). After recrystalli-
sation from DCM/n-hexane, a colourless solid (217 mg, 64%) was
obtained. Rf = 0.25 (EtOAc/MeOH, 9:1). M.p. 198–200 °C. 1H
NMR (250 MHz, [D6]DMSO): δ = 8.39–7.64 (m, 14 H, aryl-H),
7.44–7.30 (m, 4 H, aryl-H, NH), 4.31 (m, 2 H, OCH2), 4.05 (m, 1
H, OCH2CH), 3.50–3.28 (m, 3 H, aryl-CH2, NCH), 2.15 (m, 2 H,
aryl-CH2-CH2) ppm; the resonance for COOH was not observed.
13C NMR (75.4 MHz, [D6]DMSO): δ = 155.9, 143.9, 143.7, 140.6,
3330 (m), 2932 (m), 2859 (m), 1943 (w), 1712 (s), 1503 (s), 1335 (w),
1257 (m), 1105 (m), 833 (m), 775 (m), 733 (m) cm–1. C32H37NO3Si
(511.73): C 75.11, H 7.29, N 2.74; found C 75.02, H 7.19, N 2.58.
[α]2D0 = +7.9 (c = 0.95, MeOH).
Benzyl (S)-[1-(tert-Butyldimethylsilyloxymethyl)-3-(9H-fluoren-2-
yl)allyl]carbamate (4f): Vinyl compound 3 (500 mg, 1.49 mmol) was
dissolved in dry DMF (10 mL) and degassed. Then, molecular
sieves (3 Å) (500 mg), K2CO3 (500 mg, 3.60 mmol), Bu4NCl
(500 mg, 1.80 mmol), 2-bromofluorene (370 mg, 1.49 mmol) and
Pd(OAc)2 (33 mg, 0.15 mmol) were added to the solution. The mix-
ture was degassed, flushed with argon and stirred at 100 °C for
16 h. For workup, the reaction was quenched with brine and the
mixture filtered through Celite®. The filtrate was extracted three
times with EtOAc. The combined organic phases were dried with
MgSO4 and the solvents evaporated in vacuo. The residue was puri-
fied by column chromatography (n-hexane/EtOAc, 10:1). After dry-
1612
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 1608–1614